N6-methyladenosine(m6A)is recognized as the most prevalent mRNA modification in mammals, intricately involved in a multitude of processes pertaining to mRNA metabolism, encompassing RNA transcription, translation, and degradation. It plays a pivotal role in various physiological functions. Under the coordinated actions of methyltransferases, demethylases, and m6A-binding proteins, m6A modifications undergo reversible changes to fulfill their diverse molecular functions.Methyltransferase-like 3(METTL3), as the core catalytic subunit of methyltransferases and the most extensively studied methyltransferase, holds a central position in m6A modification. In recent years, it has been found that METTL3-mediated m6A modification is involved in the occurrence and development of various ocular diseases, such as ocular surface diseases, glaucoma, cataract, retinal diseases, and ocular tumors, by affecting the expression of inflammatory factors and thus regulating the inflammatory response, and by regulating various pathways that affect the proliferation of cells and oxidative stress. In this paper, we comprehensively review the mechanisms under the role of METTL3 in ocular diseases, offering novel insights and perspectives for the prevention and management of these conditions.

Liver fibrosis is a dynamic wound-healing response characterized by the agglutination of the extracellular matrix (ECM). Si-Wu-Tang (SWT), a traditional Chinese medicine (TCM) formula, is known for treating gynecological diseases and liver fibrosis. Our previous studies demonstrated that long non-coding RNA H19 (H19) was markedly upregulated in fibrotic livers while its deficiency markedly reversed fibrogenesis. However, the mechanisms by which SWT influences H19 remain unclear. Thus, we established a bile duct ligation (BDL)-induced liver fibrosis model to evaluate the hepatoprotective effects of SWT on various cells in the liver. Our results showed that SWT markedly improved ECM deposition and bile duct reactions in the liver. Notably, SWT relieved liver fibrosis by regulating the transcription of genes involved in the cytoskeleton remodeling, primarily in hepatic stellate cells (HSCs), and influencing cytoskeleton-related angiogenesis and hepatocellular injury. This modulation collectively led to reduced ECM deposition. Through extensive bioinformatics analyses, we determined that H19 acted as a miRNA sponge and mainly inhibited miR-200, miR-211, and let7b, thereby regulating the above cellular regulatory pathways. Meanwhile, SWT reversed H19-related miRNAs and signaling pathways, diminishing ECM deposition and liver fibrosis. However, these protective effects of SWT were diminished with the overexpression of H19 in vivo. In conclusion, our study elucidates the underlying mechanisms of SWT from the perspective of H19-related signal networks and proposes a potential SWT-based therapeutic strategy for the treatment of liver fibrosis.
Humans ; RNA, Long Noncoding/genetics* ; Liver Cirrhosis/genetics* ; Liver/metabolism* ; Hepatic Stellate Cells/pathology* ; MicroRNAs/metabolism* ; Extracellular Matrix/metabolism* ; Drugs, Chinese Herbal

Objective:To compare the effectiveness, safety and postoperative recurrence of percutaneous nephrolithotomy (PCNL) with Holmium laser for upper urinary calculi in Uyghur and Han pediatric patients.Methods:The data of 123 Uyghur and 71 Han pediatric patients with upper urinary calculi admitted to First People's Hospital of Kashgar, Xinjiang and Beijing Friendship Hospital, Capital Medical University respectively, from August 2018 to August 2023, were retrospectively reviewed. The gender [males 73 (59.3%) vs.46 (64.8%) ], laterality (single/bilateral: 94/29 vs. 59/12), hydronephrosis [115 (93.5%) vs. 63 (88.7%)] and anatomical abnormalities [2(1.6%) vs. 5(7.0%)] of Uyghur and Han children were not statistically significant ( P>0.05). Uyghur children were older than Han children [5 (3, 7) vs. 3 (2, 6) years old], with a higher proportion of emaciated children [27 (21.9%) vs. 6 (8.5%) cases], a larger maximum stone diameter [(2.30±0.78) vs. (1.96±1.50) cm] and a lower proportion of multiple stones [46 (37.4%) vs. 52 (73.2%) cases] (all P<0.05). All the patients were treated with Holmium laser PCNL. The channels of the procedures in this study include F12-18 small channels and visual puncture channels. The operation datas, stone-free rate (SFR), complication rate (CR) and stone recurrence rate of the two groups were compared. Meanwhile, multiple logistic regression analysis was used to explore the factors influencing these indicators. Results:The operation time for Uyghur children was significantly longer than that of Han children [75.0 (58.0, 93.0) vs. 30.0 (20.0, 48.8) min]. Additionally, a greater proportion of Uyghur children underwent PCNL with F12-18 small channels than Han children [119 (96.7%) vs. 49(69.0%) cases]. The SFR [89.4%(110/123)vs.88.7%(63/71)], and postoperative CR [31.7%(39/123)vs. 26.8%(19/71)] in Uyghur and Han patients were not significantly different (all P>0.05). The recurrence rate in Uyghur children was higher than that observed in Han children [28.1%(25/89) vs. 15.6%(10/64), P=0.033]. The multivariate logistic regression analysis results indicated that the maximum stone diameter was an independent risk factor for SFR in both groups ( OR=0.401, 95% CI 0.191-0.842, P=0.016). Similarly, maximum stone diameter ( OR=1.896, 95% CI 1.088-3.304, P=0.024) and multiple stones ( OR=3.225, 95% CI 1.409-7.384, P=0.024) were identified as independent risk factors for CR. Ethnicity was not independent risk factor for SFR( OR=0.679, 95% CI 0.215-2.140), CR( OR=1.047, 95% CI 0.495-2.215) and stone recurrence rate( OR=0.820, 95% CI 0.285-2.356, all P>0.05). Conclusions:In comparison to Han pediatric patients during the same period, Holmium laser PCNL had similar SFR and CR for treating Uyghur children with upper urinary calculi, who were older, more emaciated and had larger average stone diameters. The higher postoperative recurrence rate of Uyghur children is likely to be associated with higher stone burden. The multivariate logistic regression analysis results showed that ethnicity was not an influential factor in SFR, complication rates, and stone recurrence rates. The findings need to be further validated in larger prospective cohort studies.

OBJECTIVE: To assess the clinical efficacy and health economic value of non-invasive prenatal testing (NIPT) for the prenatal screening of common fetal chromosomal aneuploidies. METHODS: 10 612 pregnant women from October 2017 to December 2019 presented at the antenatal screening clinic of the General Hospital of Tianjin Medical University were selected as the study subjects. Results of NIPT and invasive prenatal diagnosis and follow-up outcome for the 10 612 pregnant women were retrospectively analyzed and compared. Meanwhile, NIPT data for two periods were analyzed for assessing the health economic value of NIPT as the second- or first-tier screening strategy for the prenatal diagnosis of fetal trisomies 21, 18 and 13. RESULTS: The NIPT was successful in 10 528 (99.72%) subjects, with the sensitivity for fetal trisomies 21, 18 and 13 being 100%, 92.86% and 100%, and the positive predictive value (PPV) being 89.74%, 61.90% and 44.44%, respectively. The PPV of NIPT for sex chromosome aneuploidies was 34.21%. Except for one false negative case of trisomy 18, the negative predictive value for trisomy 21, trisomy 13 and other chromosomal abnormalities were 100%. For pregnant women with high risk by serological screening, advanced maternal age or abnormal ultrasound soft markers, NIPT has yielded a significantly increased high risk ratio. There was no statistical difference in the PPV of NIPT among pregnant women from each subgroup. NIPT would have higher health economic value as a second-tier screening until 2019, while compared to 2015 ~ 2017, its incremental cost-effectiveness ratio as a first-tier screening had declined clearly. CONCLUSION The screening efficacy of NIPT for trisomies 21, 18 and 13 for a mixed population is significantly better than conventional serological screening, but it is relatively low for sex chromosomal abnormalities. NIPT can also be recommended for populations with relatively high risks along with detailed pre- and post-test genetic counselling. From the perspective of health economics, except for open neural tube defects, it is possible for NIPT to replace the conventional serological screening in the future as its cost continues to decrease.
Pregnancy ; Female ; Humans ; Trisomy/genetics* ; Retrospective Studies ; Prenatal Diagnosis/methods* ; Down Syndrome/genetics* ; Aneuploidy ; Chromosome Aberrations ; Trisomy 18 Syndrome/genetics* ; Sex Chromosome Aberrations ; Fetus

Objective:To observe any effect of virtual reality (VR) training on the cognitive functioning and functional fitness of nursing home residents with subjective cognitive decline (SCD).Methods:Fifty-six of such residents were randomly divided into an observation group and a control group, each of 28. Both groups received health education and routine care, but the observation group was additionally provided with 45 minutes of VR training three times a week for 6 months. The training included Baduanjin, magic, flying bird, supermarket shopping, gravity ball and gym episodes. Both groups′ cognition was evaluated using the subjective cognitive decline questionnaire (SCD-Q), the Montreal cognitive assessment (MoCA), the Rivermead Behavioural Memory Test (second edition) (RBMT-Ⅱ), a digit symbol substitution test (DSST), an animal fluency test (AFT) and trail-making test A-B (TMT A-B). Functional fitness was quantified using the 8-foot up-and-go test (8UGT), a 30-second arm curl test (30sACT), a 30-second chair stand test (30sCST), a back scratching test (BST), the sit-and-reach test (CSRT) and a 2-minute step test (2MST) before and after the 6-month intervention.Results:After the intervention, the average SCD-Q, MoCA, RBMT-Ⅱ, DSST, TMT-A, and TMT-B scores of the observation group were significantly better than before the intervention, and significantly better than the control group′s averages. And except for the back scratching their functional results were also significantly better, on average, than those of the control group.Conclusions:VR training can effectively improve the cognition and functional fitness of nur-sing home residents with SCD. Such training is worthy of promotion and wider application in nursing homes.

Objective:To explore the risk factors of central lymph node metastasis (CLNM) in Hashimoto thyroiditis (HT) patients with thyroid micropapillary carcinoma (PTMC), and formulate a reasonable range of lymph node.Methods:Retrospective analysis of 448 cases of PTMC admitted to the People′s Hospital of Inner Mongolia Autonomous Region from September 2018 to September 2021 including 94 males and 354 females, with a male female ratio of 1.00∶3.77, all patients aged 21 to 82 years old, with the average of (46.9 ± 11.0) years old. According to whether Hashimoto thyroiditis (HT) is combined, it is divided into HT-PTMC group ( n=142) and non HT-PTMC group ( n=306).Single factor analysis and multiple factor analysis were used to explore whether the clinicopathological characteristics of patients such as gender, age, tumor diameter, number of lesions (single/multiple lesions), presence of capsule invasion, pretracheal/paratracheal lymph nodes, delphian lymph nodes, and lateral cervical lymph nodes were related to lymph node metastasis in the central region. SPSS 20.0 software was used for statistical analysis and logistic regression equation was established, The mathematical model was used to evaluate the predictive value of diagnosis and treatment. Results:There were significant differences between HT-PTMC group and non HT-PTMC group in terms of age, sex, metastasis of anterior laryngeal lymph nodes and lateral cervical lymph nodes ( P<0.05). Univariate analysis showed that tumor diameter, number of lesions, capsule invasion, calcification, lateral cervical lymph node metastasis were correlated with CLNM in HT-PTMC patients ( P<0.05). Multivariate logistic regression analysis showed that tumor diameter increase and capsule invasion were independent risk factors for CLNM ( P<0.05). Logistic regression mathematical model was established according to the above independent risk factors: (Y=-1.974+ 0.191 × Tumor diameter+ 1.139 × The area under the ROC curve for predicting CLNM in HT-PTMC patients was 0.669 (95% CI: 0.571- 0.766). When taking the maximum Jordan index, the sensitivity of prediction was 0.460, and the specificity was 0.859. Conclusions:For PTMC patients with HT, there is evidence that the tumor diameter increases or the capsule is invaded, and the risk of lymph node metastasis in the central region is increased. Preventive lymph node dissection in the central region is recommended.

Objective:To investigate the application of multiscale low-rank plus sparsity (MLRS) modeling in fast ultra-high-field intracranial 4D Flow imaging.Methods:Ten healthy volunteers, 5 males and 5 females, aged 23-35 (29±4) years old, recruited from October 2022 to January 2023 at Huashan Hospital of Fudan University, were prospectively collected. A MLRS model acceleration algorithm was proposed according to the characteristics of 4D Flow data based on the multiscale low-rank (MLR) model. Firstly, full sampling brain 4D Flow scans were performed on healthy volunteers using 7.0 T MR, and the acquired data were under-sampled with Gaussian distributions at different acceleration rates (R of 4, 8, 12, and 16, respectively). The root mean square error (RMSE) and peak signal-to-noise ratio (PSNR) of the compressed sensing algorithm (CS), low-rank plus sparse algorithm (L+S), MLR, and MLRS model were calculated at different acceleration rates, with fully sampled data as reference. And the comparison of models was performed using the paired-samples t-test or Wilcoxon signed rank test. Pearson′s test was used to assess the correlation between hemodynamic parameters of the 4 algorithms and the fully sampled reference values at different acceleration rates, and the correlation coefficients were compared using Wilcoxon signed rank test. Results:The RMSE under the same acceleration rates was MLRS, MLR, L+S, and CS models in ascending order, and the RMSE of the MLRS model was significantly lower than that of the MLR, L+S, and CS models ( P<0.05); the PSNR was MLRS, MLR, L+S, and CS models in descending order, and the PSNR of the MLRS model was significantly higher than that of the MLR, L+S, and CS model ( P<0.05). The correlation coefficients between the blood flow velocity measured by the MLRS model and the reference value were significantly higher than those of the MLR, L+S, and CS models for different acceleration rates ( P<0.05). Conclusion:The proposed MLRS algorithm is capable of accelerating ultra-high-field 4D Flow MR imaging of the brain while guaranteeing the image quality, and the MLRS model has higher reconstruction accuracy compared with conventional acceleration models at the same acceleration rate.

Objective:To optimize indirect immunofluorescence on salt-split skin (IIF-SSS), and to evaluate its performance in detection of bullous pemphigoid (BP) antibodies.Methods:Normal human foreskin and non-foreskin skin tissues were used to prepare salt-split substrates under 3 different experimental conditions: traditional group rotated at 4 ℃ for 48 - 72 hours, low-temperature immersion group soaked at 4 ℃ for 48 - 72 hours, room-temperature immersion group soaked at 25 ℃ (range: 23 - 27 ℃) for 24 hours. Serum samples were obtained from 20 patients with bullous pemphigoid (BP) in Hospital of Dermatology, Chinese Academy of Medical Sciences between August 2019 and August 2020, and subjected to IIF on the intact skin or salt-split substrates by using a multiple dilution method. Paired-sample t test was used for comparisons of means between two paired samples. Results:No dermal-epidermal separation was observed in the substrates prepared in the low-temperature immersion group at 48 - 72 hours, while dermal-epidermal separation occurred in the lower lamina lucida of the foreskin and non-foreskin substrates in the room-temperature immersion group and the traditional group. For the 20 patients with BP, the reciprocal end-point titers ( M[ Q1, Q3]) detected with the salt-split non-foreskin skin and salt-split foreskin in the room-temperature immersion group, and with the salt-split non-foreskin skin in the traditional group were 5 120 (2 560, 17 920), 1 280 (640, 2 560), 1 280 (640, 2 560), respectively. Moreover, 19 (95%) patients with BP showed that the reciprocal end-point titers detected with the substrates in the room-temperature immersion group were 1 - 5 times those in the traditional group ( t = 8.04, P<0.001), suggesting that the performance of salt-split skin in the room-temperature immersion group was superior to that in the traditional group in the detection of BP antibodies; however, there was no significant difference in the reciprocal end-point titers of BP antibodies between the salt-split foreskin in the room-temperature immersion group and salt-split non-foreskin skin in the traditional group ( t<0.001, P>0.05). The reciprocal end-point titers in 20 BP sera detected by conventional IIF on the intact non-foreskin skin and foreskin were 320 (160, 640) and 480 (160, 1 120), respectively; the reciprocal end-point titers detected by IIF on the salt-split foreskin and non-foreskin skin in the room-temperature immersion group, as well as on the salt-split non-foreskin skin in the traditional group, were all consistent with or 1 - 7 times higher than those detected by conventional IIF ( t = 6.47, 14.83, 5.26, respectively, all P<0.001) . Conclusion:The soaking method at room temperature 25 ℃ (23 - 27 ℃) for preparing salt-split substrates has advantages of short duration and simple procedure, and the sensitivity of IIF-SSS using the substrates prepared by this method is equal or superior to the traditional salt-split method for detecting BP antibodies.

Objective:To evaluate the value of indirect immunofluorescence on salt-split skin (IIF-SSS) in the diagnosis of bullous pemphigoid (BP) .Methods:A single-center clinical retrospective study was conducted. Totally, 163 patients with newly diagnosed BP were collected from Hospital of Dermatology, Chinese Academy of Medical Sciences from January 2013 to January 2019, so were 404 controls, including 161 with pemphigus, 67 with eczema, 26 with drug eruption, 23 with erythema multiforme, 18 with prurigo nodularis, etc. Blood samples were collected before the treatment, and IIF-SSS, BP180 NC16A enzyme-linked immunosorbent assay (ELISA) and direct immunofluorescence (DIF) assay were performed to evaluate the value of IIF-SSS in the diagnosis of BP. Measurement data were compared by using t test and Mann-Whitney test, and enumeration data were compared by using chi-square test and Fisher′s exact test or McNemar test. Results:The number of cases positive for IIF-SSS, BP180 NC16A ELISA and DIF assay was 160, 153 and 127 respectively in the BP group, and 0, 18 and 26 respectively in the control group. The sensitivities of IIF-SSS, BP180 NC16A ELISA and DIF assay for the diagnosis of BP were 98.15%, 93.86% and 77.91% respectively, and their specificities were 100%, 95.54% and 93.56% respectively. There was strong consistency in the diagnosis of BP between IIF-SSS and DIF (Kappa coefficient= 0.767, P < 0.001) . Conclusion:IIF-SSS has relatively high sensitivity and specificity for the diagnosis of BP, and can serve as a routine method for diagnosing BP.

Objective: To generate a new classification for adult temporomandibular joint ankylosis (TMJA), which could effectively guide treatment strategies for adult TMJA patients with various clinical features. Methods: We developed a new "CD" classification system according to the preservation of the condyle (C) and the severity of dentofacial bone deformity (D). From January 2016 to April 2020, 56 TMJ patients (with 73 ankylosed joints) in our department were classified into 4 subgroups by ‘CD’ classification: condylar head preservation but no dentofacial deformities (C+D-), no condylar head preservation and no dentofacial deformities (C-D-), condylar head preservation and dentofacial deformities (C+ D+), and no condylar head preservation but dentofacial deformities (C-D+). Different strategies were used according to the clinical features of each subgroup. The clinical outcomes of these patients were analyzed. Different treatment strategies of temporomandibular joint reconstruction were adopted for different subclasses of patients and were followed. "C +": lateral arthroplasty (LAP) was used to remove the rigidity and preserve the medial residual condyle. "C-": if the ankylosing bone ball is small and the loss of ascending branch height is not obvious, arthroplasty should be performed to relieve ankylosis; however, if the ankylosing bone ball is large and the ascending branch height decreases significantly, joint reconstruction should be carried out after the ankylosis is relieved. "D +": surgical treatment of secondary dental and maxillofacial malformations at the same time or over stages. "D-": orthodontic treatment after operation to improve occlusal relationship and symptomatic treatment of oral diseases. Results: After treatment, all 73 ankylosed joints were completely released, and the average maximal interincisal opening increased from (3.6±3.2 )to (32.8 ± 5.4) mm (P<0.001), with no recurrence of ankylosis found during the 12-48 month follow-up period. Conclusion The generation and elaboration of a ‘CD’ classification system is intended to help as a TMJA reconstruction guide for adult TMJA treatment and be widely used in more hospitals.