AIM: To investigate the changes of microRNA-34a(miR-34a)and microRNA-29b(miR-29b)levels in lens epithelial cells of age-related cataracts(ARC)patients and their clinical significance.METHODS: A total of 65 ARC patients(study group)and 53 cases of clear lens anterior capsulorhexis(control group)who visited our hospital from February 2023 to February 2024 were gathered. Pearson was applied to test the correlation between miR-34a and miR-29b. Multifactor Logistic regression was applied to determine the factors affecting the occurrence of ARC.RESULTS: Compared with the control group, the expression levels of miR-34a and miR-29b in lens epithelial cells of the research group showed a significant decrease trend(all P<0.05). There was a positive correlation between miR-34a and miR-29b in the lens epithelial cells of ARC patients(r=0.472, P<0.05). MiR-34a and miR-29b were influence factors for ARC(all P<0.05).CONCLUSION: The levels of miR-34a and miR-29b in lens epithelial cells of ARC patients are significantly reduced, which is associated with the occurrence of ARC.

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Rapid and ultrasensitive detection of pathogen-associated biomarkers is vital for the early diagnosis and therapy of bacterial infections. Herein, we developed a close-packed and ordered Au@AgPt array coupled with a cascade triggering strategy for surface-enhanced Raman scattering (SERS) and colorimetric identification of the Staphylococcus aureus biomarker micrococcal nuclease (MNase) in serum samples. The trimetallic Au@AgPt nanozymes can catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) molecules to SERS-enhanced oxidized TMB (oxTMB), accompanied by the color change from colorless to blue. In the presence of S. aureus, the secreted MNase preferentially cut the nucleobase AT-rich regions of DNA sequences on magnetic beads (MBs) to release alkaline phosphatase (ALP), which subsequently mediated the oxTMB reduction for inducing the colorimetric/SERS signal fade away. Using this "on-to-off" triggering strategy, the target S. aureus can be recorded in a wide linear range with a limit of detection of 38 CFU/mL in the colorimetric mode and 6 CFU/mL in the SERS mode. Meanwhile, the MNase-mediated strategy characterized by high specificity and sensitivity successfully discriminated between patients with sepsis (n = 7) and healthy participants (n = 3), as well as monitored the prognostic progression of the disease (n = 2). Overall, benefiting from highly active and dense "hot spot" substrate, MNase-mediated cascade response strategy, and colorimetric/SERS dual-signal output, this methodology will offer a promising avenue for the early diagnosis of S. aureus infection.

Background::A phase II trial on recombinant human tenecteplase tissue-type plasminogen activator (rhTNK-tPA) has previously shown its preliminary efficacy in ST elevation myocardial infarction (STEMI) patients. This study was designed as a pivotal postmarketing trial to compare its efficacy and safety with rrecombinant human tissue-type plasminogen activator alteplase (rt-PA) in Chinese patients with STEMI.Methods::In this multicenter, randomized, open-label, non-inferiority trial, patients with acute STEMI were randomly assigned (1:1) to receive an intravenous bolus of 16 mg rhTNK-tPA or an intravenous bolus of 8 mg rt-PA followed by an infusion of 42 mg in 90 min. The primary endpoint was recanalization defined by thrombolysis in myocardial infarction (TIMI) flow grade 2 or 3. The secondary endpoint was clinically justified recanalization. Other endpoints included 30-day major adverse cardiovascular and cerebrovascular events (MACCEs) and safety endpoints.Results::From July 2016 to September 2019, 767 eligible patients were randomly assigned to receive rhTNK-tPA ( n = 384) or rt-PA ( n = 383). Among them, 369 patients had coronary angiography data on TIMI flow, and 711 patients had data on clinically justified recanalization. Both used a –15% difference as the non-inferiority efficacy margin. In comparison to rt-PA, both the proportion of patients with TIMI grade 2 or 3 flow (78.3% [148/189] vs. 81.7% [147/180]; differences: –3.4%; 95% confidence interval [CI]: –11.5%, 4.8%) and clinically justified recanalization (85.4% [305/357] vs. 85.9% [304/354]; difference: –0.5%; 95% CI: –5.6%, 4.7%) in the rhTNK-tPA group were non-inferior. The occurrence of 30-day MACCEs (10.2% [39/384] vs. 11.0% [42/383]; hazard ratio: 0.96; 95% CI: 0.61, 1.50) did not differ significantly between groups. No safety outcomes significantly differed between groups. Conclusion::rhTNK-tPA was non-inferior to rt-PA in the effect of improving recanalization of the infarct-related artery, a validated surrogate of clinical outcomes, among Chinese patients with acute STEMI.Trial registration::www.ClinicalTrials.gov (No. NCT02835534).

ObjectiveThis paper aims to analyze the clinical characteristics and medication rationality of liver injury related to Epimedii Folium preparation （EP） and explore the possible risk factors of liver injury， so as to provide a reference for the safe clinical application of Epimedii Folium （EF）. MethodA retrospective analysis was conducted on liver injury cases related to EP from 2012 to 2016. ResultThe number of reported liver injury cases and the proportion of severe cases related to the use of EP show an increasing trend， indicating the objective existence of liver injury caused by EP. There are more cases of liver injury related to EP in women than in men， with an onset age range of 15-91 years old and a median onset age of 60 years old （median onset ages for men and women are 59 and 60 years old， respectively）. The time span from taking EP alone to the occurrence of liver injury is 1-386 days， with a median of 38 days. The time span from taking both EP and Western medicine to the occurrence of liver injury is 1-794 days， with a median of 34 days. EF-related liver injury preparations are mostly composed of traditional Chinese medicines that promote immunity and tonify the liver and kidney， indicating that immune stress in the body may be the mechanism of liver injury caused by the use of EP alone or in combination. There is no increasing trend of toxicity with time or dose in the liver injury caused by EP. By further exploring its risk factors， it is found that patients have unreasonable medication methods such as excessive dosage， repeated use， and multi-drug combination， which may also be one of the important risk factors for EF-related liver injury. ConclusionEP has a certain risk of liver injury and should be emphasized in clinical diagnosis and treatment. Immune stress may be the mechanism of liver injury caused by EP， and in clinical use， it is necessary to be vigilant about the risk of liver injury caused by unreasonable use and combined use with Western medicine.

Objective To analyze the characteristics of platelet changes and their influencing factors during postoperative hospitalization in patients who underwent transcatheter aortic valve implantation (TAVI). Methods The patients who underwent TAVI at Beijing Anzhen Hospital Valve Surgery Center between March 2017 and October 2021 were retrospectively selected. The patients were divided into a self-limiting group and a non-self-limiting group according to the characteristics of postoperative platelet decline. In addition, the general preoperative data, preoperative and postoperative ultrasound data, intraoperative data, and the use of anticoagulant drugs during the postoperative stay in the hospital were compared between the two groups. Results A total of 249 patients were enrolled in this study. There were 175 (70.3%) patients in the self-limiting group, including 100 males and 75 females, and there were 74 (29.7%) patients in the non-self-limiting group, including 43 males and 31 females, with no statistical difference between the two groups (P=0.863). The mean age of patients was 73.11±8.88 years in the self-limiting group and 71.54±10.39 years in the non-self-limiting group (P=0.231). The decline of platelets in the self-limiting group generally occurred on the postoperative day 2 and reached the lowest count on the postoperative day 4, and returned to the baseline level on the postoperative day 5-7, while the platelets in the non-self-limiting group changed by simple rise, fall or irregular fluctuation. Patients in the self-limiting group had severer preoperative aortic stenosis (P<0.001) and used more extracorporeal circulation assistance during surgery (P<0.001). Postoperatively, patients in the self-limiting group were more likely to have periaortic valve leakage than those in the non-self-limiting group (P=0.013). Conclusion Platelet changes in most patients after TAVI show a self-limiting decline, which may be related to the severity of patients’ preoperative aortic stenosis, intraoperative extracorporeal circulation device use, and postoperative perivalvular leakage.

Objective To investigate T cell subtypes and their functions in liver immune microenvironments among patients with alveolar echinococcosis (AE) using single-cell RNA sequencing (scRNA-seq). Methods Four AE patients that were admitted to Qinghai Provincial People’s Hospital in 2023 for hepatic surgery for the first time were enrolled, and liver specimens were sampled 1 cm (peri-lesion, PL group) and > 5 cm from AE lesions (distal lesion, DL group) among each patient. Finally, a total of eight liver specimens were sampled from four AE patients for scRNA-seq analysis. Genome and transcriptome data of liver specimens were processed using the software Cell Ranger and R package. Differentially expressed genes (DEGs) and their biological functions were analyzed using gene ontology (GO) enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis, and the primary intercellular communication patterns and interaction mechanisms were identified among T cell subtypes in liver specimens using the CellChat package. In addition, the developmental stages of T cells were subjected to trajectory analysis with the monocle package to investigate the expression of genes associated with cell growth and tumor transformation, and to predict the developmental trajectories of T cells. Results All four AE patients were female, with a mean age of (25.00 ± 9.06) years, and there were three cases from Jiuzhi County, Golog Tibetan Autonomous Prefecture and one case from Chengduo County, Yushu Tibetan Autonomous Prefecture, Qinghai Province. The viability of single-cell samples from eight liver specimens was 90.41% to 96.33%, and a total of 81 763 cells were analyzed, with 19 cell types annotated. Of these cell types, 13 were immune cells (87.60%), and T cells (33.13%), neutrophils (15.40%), and natural killer cells (11.92%) were the three most common cell types. Re-clustering of 27 752 T cells and proliferative T cells identified 10 distinct T cell subtypes, with CD8⁺ cytotoxic T cells (23.43%), CD8⁺ naive T cells (12.80%), and CD4⁺ effector memory T cells (17.73%) as dominant cell types. The proportions of T helper 2 (Th2) cells (5.19% vs. 3.63%; χ² = 38.35, P < 0.01) and CD4⁺ effector memory T cells (21.59% vs. 13.67%; χ² = 244.70, P < 0.01) were significantly higher in liver specimens in the PL group than in the DL group, and the proportion of CD4⁺ helper T cells was significantly lower in the PL group than in the DL group (7.50% vs. 14.75%; χ² = 330.52, P < 0.01). KEGG pathway analysis revealed that Th2 cells were significantly enriched in cell apoptosis and multiple cancer-associated pathways, and CD4⁺ effector memory T cells were significantly enriched in the regulation of cytokines and chronic inflammation, while CD4⁺ helper T cells were significantly enriched in immune responses regulation. Trajectory analysis of T cells showed that CD4⁺ helper T cells were at an earlier developmental stage relative to Th2 cells and CD4⁺ effector memory T cells, and the expression of inhibitor of DNA binding 3 (ID3), thioredoxin interacting protein (TXNIP), Bcl2-associated athanogene 3 (BAG3) and heat shock protein family B (small) member 1 (HSPB1) genes appeared a tendency towards a decline over time. Conclusions CD4⁺ effector memory T cells and CD8⁺ cytotoxic T cells are primary interacting cells in the liver specimens of AE patients. Reduced expression of Th2 cells and CD4⁺ helper T cells contributes to an inhibitory immune microenvironment, which promotes immune evasion by Echinococcus multilocularis, and Th2 cells are significantly enriched in multiple cancer-associated pathways, which may be linked to the invasive growth of E. multilocularis.

BACKGROUND:At present,measurement osteotomy technique and gap balance technique are the two main surgical methods in total knee arthroplasty.Both methods have their advantages and disadvantages.By adjusting the osteotomy angle,the gap balance technique can reduce the release of soft tissue and obtain a more balanced flexion and extension space.The clinical efficacy of gap balance technique is superior,but this surgical method lacks tools and is easily influenced by the surgeon's surgical experience and subjective judgment,with more errors.Measurement osteotomy technique has a short learning curve,but it relies on anatomic markers and is prone to many complications due to inaccurate positioning.In recent years,many instrument companies have successively developed and launched tools that can improve the quality of surgery.However,there are still few reports about the tool. OBJECTIVE:To compare the clinical efficacy of gap balance technique and measurement osteotomy technique under Offset Repo-Tensor in total knee arthroplasty,and explore the value of Offset Repo-Tensor in total knee arthroplasty. METHODS:The medical records of 85 patients with total knee arthroplasty were collected and divided into two groups according to the operation method.Group A consisted of 44 patients who underwent total knee arthroplasty using a gap balance technique combined with Offset Repo-Tensor.Group B consisted of 41 patients who underwent total knee arthroplasty using measurement osteotomy technique.Surgical time,American Knee Society Score,knee range of motion,changes in lower limb alignment,and postoperative complications were compared between the two groups to evaluate the clinical efficacy of gap balance technique combined with Offset Repo-Tensors in total knee arthroplasty. RESULTS AND CONCLUSION:(1)All 85 patients were followed up.(2)Postoperative knee range of motion in both groups was higher than that before surgery(P<0.05),and the improvement in group A was more significant than that in group B(P<0.05).(3)American Knee Society Score in both groups after surgery was higher than that before surgery(P<0.05),and the American Knee Society Score in group A was higher than that in group B at 2 weeks,1,3 months,and the last follow-up(P<0.05).(4)The operation time of group A was slightly shorter than that of group B,but the difference was not significant(P>0.05).(5)The lower limb alignment in both groups was improved after operation,but there was no significant difference between the two groups(P>0.05).(6)The complication rate of group A(2%)was lower than that of group B(7%),but there was no significant difference between the two groups(P>0.05).(7)It is indicated that compared with the measurement osteotomy technique,the combination of Offset Repo-Tensor and gap balance technique can elevate the clinical effect and improve the function and motion range of the knee joint.

Objective:To explore the genetic etiology for a child with Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 6 (PEOA6).Methods:A child who had attended the Women and Children′s Hospital Affiliated to Ningbo University on 7 August, 2023 was selected as the study subject. Clinical data of the child were analyzed retrospectively. The child and her parents were subjected to whole exome sequencing (WES), and candidate variant was verified by Sanger sequencing and bioinformatic analysis. This study was approved by Medical Ethics Committee of the Women and Children′s Hospital Affiliated to Ningbo University (Ethics No. EC2020-048).Results:The child, a 7-year-old female, had presented with limb muscle pain, amyosthenia, significantly increased creatine kinase, congenital diaphragmatic hernia and recurrent respiratory tract infections. WES revealed that she has harbored a heterozygous c. 1590G>C (p.L530F) variant of the DNA2 gene, which was verified to have a de novo origin by Sanger sequencing. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.1590G>C was rated as a likely pathogenic variant (PS2+ PM2_Supporting+ PP3). Conclusion:The c.1590G>C (p.L530F) variant of the DNA2 gene probably underlay the PEOA6 in this child.