AIM: To investigate the influencing factors of stereoscopic function reconstruction after intermittent exotropia(IXT)surgery and the construction of a nomogram prediction model.METHODS:A total of 204 patients with IXT(all underwent strabismus correction surgery)admitted to our hospital from September 2021 to October 2023 were randomly divided into modeling group(143 cases)and validation group(61 cases). The patients in the modeling group were further divided into reconstructive group and non-reconstructive group according to whether they had stereoscopic function reconstruction after surgery; the general patient information was collected; Multivariate Logistic regression analysis was performed on the influencing factors of stereoscopic visual function reconstruction after IXT surgery. The nomogram model was constructed using R software. The ROC curve was drawn to evaluate the distinction of the nomogram model. The decision curve analysis(DCA)was used to evaluate the clinical application value of the model.RESULTS:Reconstruction occurred in 50.5%(103 cases)of the 204 patients, and reconstruction occurred in 50.3%(72 cases)of the 143 patients in the modeling group. There were differences in age of onset, course of disease and postoperative horizontal strabismus between the reconstructive group and the non-reconstructive group(all P<0.05). Multivariate Logistic regression analysis showed that age of onset and postoperative horizontal strabismus were risk factors for stereoscopic visual function reconstruction after IXT surgery(all P<0.05), and the course of disease was a protective factor(P<0.05). The AUC of the modeling group was 0.892, and the H-L test was χ2=6.654 and P=0.615. The AUC of the validation group was 0.935, and the H-L test was χ2=6.498 and P=0.642. The DCA curve showed that the clinical value of the nomogram model was higher when the probability was 0.09-0.95.CONCLUSION: The age of onset, course of disease and postoperative amount of horizontal strabismus are the influencing factors of stereoscopic visual function reconstruction after IXT surgery, and the nomogram model constructed by this can better predict postoperative stereoscopic function reconstruction.

OBJECTIVE: To explore the clinical and genetic features of a child with Pontocerebellar hypoplasia type 2B (PCH2B) due to compound heterozygous variants of the TSEN2 gene. METHODS: A PCH2B patient presented at Department of Pediatric Neurology, Xiangya Hospital of Central South University in June 2023 was selected as the study subject. Clinical data of the patient were retrospectively analyzed. The patient and her parents were subjected to whole exome sequencing and bioinformatic analysis. Pathogenicity of the candidate variants were classified based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). A literature review was also conducted by searching the China National Knowledge Infrastructure (CNKI), Wanfang Data, and PubMed databases from their establishment to May 2025 using keywords "TSEN2 gene" "PCH2B" and "Pontocerebellar Hypoplasia 2B" to summarize the clinical and genotypic features of patients with PCH2B due to variants of the TSEN2 gene. This study was approved by the Medical Ethics Committee of the Hospital (No.: #202310892). RESULTS: The patient, a 6-year-5-month-old girl, had exhibited severe global developmental delay, developmental regression, autism spectrum disorder, myoclonus of eyelids, feeding difficulty, irritability, progressive microcephaly, esotropia, and hypotonia. MRI showed reduced volume of bilateral cerebellar hemispheres and vermis. Genetic testing revealed that she has harbored compound heterozygous variants of the TSEN2 gene (NM_025265.4), namely c.1054A>T (p.Lys352*) and c.899G>T (p.Ser300Ile), which were inherited from her father and mother, respectively. Both variants were classified as likely pathogenic based on the ACMG guidelines and were previously unreported. Literature review has identified six PCH2B patients with missense, nonsense, frameshift, and splice site variants of the TSEN2 gene. Their main clinical manifestations included global developmental delay, progressive microcephaly, feeding difficulties, irritability, and vermis hypoplasia. Cranial MRI and genetic testing are crucial for definite diagnosis. CONCLUSION The c.1054A>T (p.Lys352*) and c.899G>T (p.Ser300Ile) compound heterozygous variants of the TSEN2 gene probably underlay the pathogenesis in this patient. Above findings has expanded the genotypic and phenotypic spectra of TSEN2-related PCH2B, and offered guidance for genetic counseling for this family.
Child ; Female ; Humans ; Cerebellar Diseases/genetics* ; Exome Sequencing ; Heterozygote ; Mutation

Histone deacetylase has proved to be a promising new antimalarial target in the development of novel antimalarial drugs. This article introduces the mechanism of action of histone deacetylase inhibitors and their antimalarial activity, with a focus on the discovery process of Plasmodium histone deacetylase inhibitors and their recent research progress both domestically and internationally. Recent research findings on hydroxamic acid-based and cyclic peptide inhibitors are reviewed and analyzed in detail according to their different structural types. Key challenges hindering drug development and approval, such as drug toxicity issues and the lag in related biological studies, are highlighted. Furthermore, future directions for drug research and development are proposed, offering insights for the further development of new antimalarial drugs.

Objective: To compare the consistency between bioelectrical impedance analysis (BIA) and dual energy X ray absorptiometry (DXA) in measuring body composition among Tibetan children and adolescents and to explore the applicability of BIA in plateau region, so as to provide scientific and convenient body composition measurement support among children and adolescents. Methods: From May to June, 2022, a total of 344 Tibetan children and adolescents aged 6-17 years were selected from Golmud Municipal National Middle School and Changjiangyuan Nationality Primary School in Qinghai Province by cluster sampling method, and their fat mass, fat mass percentage and lean mass were measured by DXA and BIA. The consistency and correlation between the two methods were assessed by using the Wilcoxon rank-sum test, Spearman correlation analysis, intraclass correlation coefficient (ICC), and Bland-Altman analysis. Results: DXA measured fat mass and fat mass percentage were significantly higher than those obtained by BIA (6-12 years old: Z =9.91, 11.28; 13-17 years old: Z =9.02, 10.21), while lean mass and lean mass percentage were significantly lower than BIA results (6-12 years old: Z =-11.60, -11.30; 13-17 years old: Z =-10.77, -10.36) (all P < 0.05 ). The two methods showed strong correlations in fat mass and lean mass (all r >0.80, all ICC >0.90), but exhibited poor agreement in fat mass percentage and lean mass percentage (6-12 years old: Lin s CCC =0.64, 0.41; 13-17 years old: Lin s CCC = 0.79 , 0.35). Bland-Altman analysis showed that the difference between the two methods was negatively correlated with the average value in FM%(6-12 years old: r =-0.75, 13-17 years old: r =-0.79, both P <0.01). Conclusion BIA and DXA show high consistency in measuring body fat mass and lean body mass in Tibetan children and adolescents, although some bias is still present in certain individuals.

Objective: To understand the epidemiological characteristics and disease burden of influenza like illness (ILI) among student populations, so as to provide data support for policy formulation and optimal allocation of health resources. Methods: From January 2024 to February 2025, a questionnaire survey was conducted among parents of kindergarten, primary school, junior and senior high school students in 9 districts of Shenzhen, including Longhua, Futian, Bao an, Longgang, Luohu, Nanshan, Guangming, Pingshan and Yantian. Parents were asked to complete the questionnaire based on whether their children had fever, cough, vomiting, diarrhea, rash and other common symptoms in 2024. A total of 3 537 parents were investigated, and 444 ILI cases were included as study subjects. The epidemiological burden, including incidence rate of influenza, visitation rate, years lived with disability (YLDs) and economic burden (including direct economic burden, indirect economic burden and intangible burden) were analyzed. Results: The incidence rate of influenza among students in Shenzhen in 2024 was 12.55%. The ILI incidence rates in kindergarten, primary school, junior and senior high school were 14.01%, 11.69% and 5.23%, respectively, with a statistically significant difference ( χ 2= 45.20, P <0.01). The ILI consultation rate among students was 85.36%, and the consultation rates in kindergarten (87.36%) and primary school students (84.62%) were higher than those in junior and senior high school students ( 56.52 %) ( χ 2=16.47, P <0.01). A total of 78.88% of cases did not receive etiological detection.The median total economic burden per ILI case was 2 354.62 yuan, including direct medical costs of 300.00 yuan, direct non medical costs of 212.50 yuan, indirect costs of 1 000.00 yuan, and intangible burden of 500.00 yuan. Conclusions Schools are high risk environment for influenza, and younger students are a high risk group for ILI. The disease burden caused by student ILI remains substantial.

Objective To examine the impact of extreme temperature and drought stress on the survival of Bulinus globosus, so as to provide the theoretical evidence for the genomic research of Bulinus in absence of reference genes. Methods B. globosus snail samples were collected from Kiwani Shehia in Pemba Island, Zanzibar, Tanzania, and offspring snails were obtained through laboratory breeding and reproduction. A total of 120 10-week-old B. globosus snails from the same generation were selected and randomly assigned into four groups, including the high-temperature drought (HD) group, normal temperature drought (D) group, low-temperature drought (LD) group, and the control (C) group, of 30 snails in each group. Snails in HD, D, and LD groups were placed in beakers containing dry soil at the bottom and subsequently housed in climate chambers at 35, 26 ℃, and 10 ℃, respectively, while snails in Group C were maintained in 500 mL petri dishes containing dechlorinated tap water at 26 ℃. Following 3 days of breeding, living snails in each group were collected, and soft tissues were dissected and isolated. Total RNA was extracted from snail soft tissues for library construction, followed by high-throughput sequencing on the Illumina HiSeq 4000 sequencing system. De novo transcriptome assembly was performed using the Trinity software, and the longest transcripts were selected as unigenes. Gene functional annotations of unigenes were conducted using the Diamond software against Gene Ontology (GO) knowledgebase, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database, NCBI non-redundant (NR) protein sequences database, Protein Family (Pfam) database, and UniProtKB/Swiss-Prot (Swiss-Prot) knowledgebase. GO and KEGG enrichment analyses of differentially expressed genes (DEGs) were performed using the topGO and clusterProfiler software, respectively. In addition, four relevant genes were selected for validation using a real-time quantitative PCR (qRT-PCR) assay to verify the reliability of transcriptome sequencing results. Results Following 3 days of breeding, there were 7, 20, 28, and 30 survival B. globosus snails in HD, LD, D, and C groups, with corresponding survival rates of 23.33% (7/30), 66.67% (20/30), 93.33% (28/30), and 100.00% (30/30), respectively (χ² = 52.72, P < 0.001). De novo transcriptome assembly generated 176 942 unigenes, with annotation rates of 0.98%, 13.49%, 26.46%, 12.48%, and 14.39% against GO knowledgebase, KEGG pathway database, NR protein sequences database, Pfam database, and Swiss-Prot knowledgebase, respectively. There were 33 up-regulated and 72 down-regulated genes in Group D, 483 up-regulated and 815 down-regulated genes in Group HD, and 245 up-regulated and 172 down-regulated genes in Group LD relative to in Group C. Following removal of overlapping genes across groups and unmatched genes, 11 candidate genes were identified. GO and KEGG analyses revealed 3 heat shock protein (HSP)-related DEGs in these 11 candidate genes, which were annotated as HSP12.2, HSP70, and HSP20 genes and were all significantly up-regulated in each treatment group. Three immune and nervous system-related DEGs were identified, and were all significantly down-regulated in each treatment group, which were involved in the neural cell adhesion molecule L1-like protein pathway, fibrinogen binding protein pathway, and leukocyte elastase inhibitor-like protein pathway. qRT-PCR assay quantified that the expression trends of four genes related to temperature and drought stress across different treatment groups were highly consistent with transcriptome sequencing data. Conclusion The survival rate of B. globosus significantly reduces under combined stresses of extreme temperature and drought, possibly due to an imbalance in its cellular homeostasis regulatory system.

The frequent extreme climatic events post multifaceted impacts on the distribution of Oncomelania hupensis, the intermediate host of Schistosoma japonicum in the context of global climate change. This article systematically reviews the effects of four types of extreme climatic events, including floods, droughts, heat waves, and cold waves, on the survival, reproduction, and distribution of Oncomelania hupensis. Floods may expand suitable snail habitats, and increase both emerging and re-emerging snail habitats; however, the impact of floods on O. hupensis density is characterized by a lag effect of a decline followed by a rise. Droughts may cause fragmentation of suitable O. hupensis snail habitats, reduced O. hupensis snail egg production rates, and increased O. hupensis snail mortality, and heat waves may cause an increase in O. hupensis snail mortality, a reduction in numbers of O. hupensis snail populations and shrinking of O. hupensis snail distribution, while cold waves may cause a reduction in O. hupensis snail density and a rise in O. hupensis snail mortality. Extreme climate events pose both shortand long-term effects on the distribution of O. hupensis. Intensified surveillance of O. hupensis snails is required in high-risk environments.

Osteoarthritis (OA), a highly prevalent degenerative joint disease worldwide, is defined by articular cartilage degradation, abnormal bone remodeling, and persistent chronic inflammation. It severely compromises patients’ quality of life, and currently, there is no radical cure. Abnormal mechanical stress is widely regarded as a core driver of OA pathogenesis, and the exploration of mechanical signal perception and transduction mechanisms has become crucial for deciphering OA’s pathophysiological processes. Piezo1, a key mechanosensitive cation channel belonging to the Piezo protein family, has recently gained significant attention due to its pivotal role in mediating cellular responses to mechanical stimuli in joint tissues. This review systematically examines Piezo1’s expression patterns, regulatory mechanisms, and pathological functions in OA, with a particular focus on its dual roles in modulating chondrocyte homeostasis and bone metabolism disorders, while also delving into the underlying molecular signaling pathways and potential therapeutic implications. Piezo1, consisting of approximately 2 500 amino acids and forming a unique trimeric propeller-like structure, is widely expressed in chondrocytes, osteocytes, mesenchymal stem cells, and synovial cells. It exhibits permeability to cations such as Ca²⁺, K⁺, and Na⁺, and directly responds to membrane tension changes induced by mechanical stimuli like fluid shear stress and mechanical overload. In OA patients and animal models, Piezo1 expression is significantly upregulated, especially in cartilage regions subjected to abnormal mechanical stress (e.g., human temporomandibular joint cartilage). This overexpression is closely associated with aggravated cartilage degeneration, increased chondrocyte apoptosis, accelerated cellular senescence, and intensified inflammatory responses. Mechanical overload and pro-inflammatory cytokines (e.g., IL-1β) are key inducers of Piezo1 upregulation: IL-1β activates the PI3K/AKT/mTOR signaling pathway to enhance Piezo1 expression, forming a pathogenic positive feedback loop that inhibits chondrocyte autophagy, promotes apoptosis, and further accelerates joint degeneration. Mechanistically, Piezo1 mediates OA progression through multiple interconnected pathways. When activated by mechanical stress, Piezo1 triggers excessive Ca²⁺ influx, leading to endoplasmic reticulum stress (ERS) and mitochondrial dysfunction, which directly induce chondrocyte apoptosis. This process involves the activation of downstream signaling cascades such as cGAS-STING and YAP-MMP13/ADAMTS5. YAP, a transcriptional regulator, upregulates the expression of matrix metalloproteinase 13 (MMP13) and aggrecanase (ADAMTS5), thereby accelerating cartilage matrix degradation. Additionally, Piezo1-driven Ca²⁺ overload promotes the accumulation of reactive oxygen species (ROS) and upregulates senescence markers (p16 and p21), accelerating chondrocyte senescence via the p38MAPK and NF-κB pathways. Senescent chondrocytes secrete senescence-associated secretory phenotype (SASP) factors (e.g., IL-6, IL-1β), further amplifying joint inflammation. In terms of bone metabolism, Piezo1 maintains joint homeostasis by promoting the differentiation of fibrocartilage stem cells into chondrocytes and balancing bone formation and resorption through regulating the FoxC1/YAP axis and RANKL/OPG ratio. Therapeutically, targeting Piezo1 shows promising potential. Preclinical studies have demonstrated that Piezo1 inhibitors (e.g., GsMTx4) can reduce joint damage and alleviate pain in OA mice. Simultaneously, siRNA-mediated co-silencing of Piezo1 and TRPV4 (another mechanosensitive channel) decreases intracellular Ca²⁺ concentration, inhibits chondrocyte apoptosis, and promotes cartilage repair. Conditional knockout of Piezo1 using Gdf5-Cre transgenic mice alleviates cartilage degeneration in post-traumatic OA models by downregulating MMP13 and ADAMTS5 expression. Despite existing challenges, such as off-target effects of inhibitors, inefficient local drug delivery, and interindividual genetic variability, strategies like developing selective Piezo1 antagonists, optimizing targeted nanocarriers, and combining Piezo1-targeted therapy with physical therapy provide viable avenues for clinical translation. The authors propose that Piezo1 serves as a critical therapeutic target for OA, and future research should focus on deciphering its context-dependent regulatory networks, developing tissue-specific intervention strategies, and validating their efficacy and safety in clinical trials to address the unmet medical needs of OA patients.

ObjectivePhotoacoustic tomography (PAT) holds significant potential for high-resolution deep-tissue imaging. In preclinical research, custom-designed concave arc-shaped ultrasound transducer arrays are often used to maximize the detection aperture. However, manufacturing limitations and assembly tolerances frequently cause the actual physical positions of array elements to deviate from their theoretical design. Additionally, concave arrays are typically covered with an acoustic lens, which introduces a mismatch in the speed of sound between the coupling medium and the lens material. The combination of these geometric and acoustic-phase errors leads to severe image artifacts, reduced contrast, and degraded resolution. This study proposes a systematic two-step calibration strategy to address these issues and substantially improve image quality. MethodsFirst, a high-intensity isotropic photoacoustic point source was constructed using a multi-mode optical fiber coated with carbon nanotubes (CNTs) to acquire high signal-to-noise ratio calibration data. The Akaike information criterion (AIC) was employed to accurately determine the time of arrival (ToA) of photoacoustic signals. Subsequently, a geometric calibration algorithm based on nonlinear least-squares (NLS) estimation was developed. This algorithm iteratively solves for the true spatial coordinates of each array element by minimizing the residual between theoretical and measured acoustic path lengths. To further address sound-speed inhomogeneity caused by the acoustic lens, a phase compensation algorithm based on bilinear interpolation was proposed. This algorithm computes a pixel-specific phase delay map across the imaging region and performs point-by-point signal correction during delay-and-sum (DAS) reconstruction. The proposed methods were validated using a custom 96-channel concave arc-shaped array (center frequency: 12  MHz) through both phantom imaging and in vivo mouse tumor models. ResultsPhantom experiments showed that at an imaging depth of14 mm, the reconstruction position deviation of the point source in the uncalibrated system reached up to 1  mm. After applying the combined calibration, the lateral resolution (full width at half maximum, FWHM) at the focal point of the arc array reached 95  μm—representing a 85% reduction compared to the uncalibrated state and a 79% reduction compared to geometric calibration alone without phase compensation. In vivo experiments demonstrated that the calibrated system clearly resolved the microvascular network of subcutaneous tumors in mice. Photoacoustic signals were strictly confined within tumor boundaries delineated by ultrasound imaging (USI), eliminating the vascular spillover artifacts commonly observed in uncalibrated images. Furthermore, after intravenous injection of indocyanine green (ICG), the system successfully detected weak photoacoustic signals at a depth of 5 mm, performing significantly better than the uncalibrated system. ConclusionThe proposed calibration method, which integrates nonlinear least-squares estimation with phase compensation, significantly improves image fidelity and spatial resolution consistency across a wide field of view by correcting systemic geometric errors and acoustic phase aberrations. This approach demonstrates high robustness and provides a reliable technical foundation for the clinical translation of photoacoustic probes with non-standard geometries.

Wilson disease （WD） is one of the few treatable neurogenetic disorders. Currently， Western medicine remains the main treatment method for WD， while since the 1990s， multiple studies conducted by Professor Yang Renmin and his team have shown that traditional Chinese medicine （TCM） also has a favorable therapeutic effect. Based on the principle of low-copper diet for WD， this article systematically elaborates on the advantages， limitations， and key considerations of current Western medicine therapies （pharmacotherapy， liver transplantation， and splenectomy） and reviews the research findings of TCM in China， especially the wide application of Gandou Decoction in clinical practice. Studies have shown that Gandou Decoction can effectively improve neurological symptoms， protect hepatic and renal function， and avoid the adverse drug reactions associated with metal chelating agents， and therefore， it can be used an effective long-term adjuvant therapy for WD. It should be noted that symptoms and signs should be considered in integrated traditional Chinese and Western medicine therapy for WD， and high-copper TCM drugs should be avoided to prevent deterioration.