Intermittent exotropia(IXT)is the most prevalent form of childhood strabismus, with an estimated prevalence of approximately 3.26% in the Chinese population. Although patients can intermittently maintain orthotropia, the deviation angle often fluctuates markedly, and frank exotropia may become evident during fatigue or lapses in attention. Without intervention, roughly 75% of cases progress over time. Management comprises surgical and non-surgical approaches. Surgery remains the most definitive treatment, however, the optimal timing is controversial, and postoperative outcomes may include under- or over-correction, necessitating additional procedures. Non-surgical options include observation, refractive correction, over-minus lens therapy, prisms, orthoptic exercises, and botulinum toxin-A injections. These modalities are particularly suitable for young, or uncooperative children, patients with small-angle, well-controlled deviations, or those seeking to defer surgery, in such cases, non-surgical treatment can maintain binocular alignment and preserve monocular function, thereby delaying or avoiding surgery. Because the efficacy of each non-surgical strategy varies, this review summarizes the current evidence on non-surgical treatment of IXT.

ObjectiveTo examine the influences of Shenfu injection on the endogenous metabolic byproducts in the myocardium of the rat model exhibiting chronic heart failure， thus deciphering the therapeutic mechanism of the Qi-reinforcing and Yang-warming method. MethodsSD rats were randomly allocated into a control group and a modeling group. Chronic heart failure with heart-Yang deficiency syndrome in rats was modeled by multi-point subcutaneous injection of isoproterenol， and the rats were fed for 14 days after modeling. The successfully modeled rats were randomized into model， Shenfu injection （6.0 mL·kg^-1）， and trimetazidine （10 mg·kg^-1） groups and treated with corresponding agents for 15 days. The control group and the model group were injected with equal doses of normal saline， and the samples were collected after the intervention was completed. Cardiac color ultrasound was performed. Hematoxylin-eosin （HE） staining was used to observe histopathological morphology， and the serum level of N-terminal pro-brain natriuretic peptide （NT-proBNP） was assessed by enzyme-linked immunosorbent assay （ELISA）. The mitochondrial morphological and structural changes of cardiomyocytes were observed by transmission electron microscopy， and the metabolic profiling was carried out by ultra high performance liquid chromatography-quantitative exactive-mass spectrometry （UHPLC-QE-MS）. Differential metabolites were screened and identified by orthogonal partial least squares-discriminant analysis （OPLS-DA） and other methods， and then the MetaboAnalyst database was used for further screening. The relevant biological pathways were obtained through pathway enrichment analysis. The receiver operating characteristic （ROC） curve was established to evaluate the diagnostic value of each potential biomarker for myocardial injury and the evaluation value for drug efficacy. ResultsThe results of color ultrasound showed that Shenfu Injection improved the cardiac function indexes of model rats （P<0.05）. The results of HE staining showed that Shenfu injection effectively alleviated the pathological phenomena such as myocardial tissue structure disorder and inflammatory cell infiltration in model rats. The results of ELISA showed that Shenfu injection effectively regulated the serum NT-proBNP level in the model rats. Transmission electron microscopy （TEM） showed that Shenfu injection effectively restored the mitochondrial morphological structure. The results of metabolomics showed that the metabolic phenotypes of myocardial samples presented markedly differences between groups. Nine differential metabolites could be significantly reversed in the Shenfu injection group， involving three metabolic pathways： pyruvate metabolism， histidine metabolism， and citric acid cycle （TCA cycle）. The results of ROC analysis showed that the area under the curve （AUC） values of all metabolites were between 0.75 and 1.0， indicating that the differential metabolites had high diagnostic accuracy for myocardial injury， and the changes in their expression levels could be used as potential markers for efficacy evaluation. ConclusionShenfu injection significantly alleviated the damage of cardiac function， myocardium， and mitochondrial structure in the rat model of chronic heart failure with heart-Yang deficiency syndrome by ameliorating energy metabolism remodeling. Reinforcing Qi and warming Yang is a key method for treating chronic heart failure with heart-Yang deficiency syndrome.

Objective To explore the relationship between circadian rhythm genes and the occurrence, development, prognosis, and tumor microenvironment (TME) of lung adenocarcinoma (LUAD). Methods The Cancer Genome Atlas data were used to evaluate the expression, copy number variation, and somatic mutation frequency of circadian gene sets in LUAD. Gene ontology, Kyoto encyclopedia of genes and genomes, and gene set enrichment analysis were used to explore the potential mechanisms by which circadian rhythm genes affected LUAD progression. Cox regression, least absolute shrinkage and selection operator regression, support vector machine recursive feature elimination, and random forest screened circadian genes and established prognostic models, and on this basis constructed nomogram to predict patients’ 1-, 3-, and 5-year survival rates. Kaplan-Meier survival curves, receiver operating characteristic (ROC) curves, and time-dependent ROC curves were drawn to evaluate the predictive ability of the model, and the external dataset of GEO further verified the prognostic value of the prediction model. In addition, we evaluated the association of the prognostic model with immune cells and immune checkpoint genes. Single cell RNA sequencing (scRNA-seq) analysis was used to explore the molecular characteristics between prognostically relevant circadian genes and different immune cell populations in TME. Results Differentially expressed circadian rhythm genes were mainly enriched in biological processes related to cGMP-PKG signaling pathway, lipid and atherosclerosis, and JAK-STAT signaling pathway. Seven circadian rhythm genes: LGR4, CDK1, KLF10, ARNTL2, RORA, NPAS2, PTGDS were screened out, and a RiskScore model was established. According to the median RiskScore, samples were divided into a high-risk group and a low-risk group. Compared with patients in the low-risk group, patients in the high-risk group showed a poorer prognosis (P<0.001). Immunological characterization analysis showed that there were differences in the infiltration of multiple immune cells between the low-risk group and high-risk group. Most immune checkpoint genes had higher expression levels in the high-risk group than those in the low-risk group, and RiskScore was positively correlated with the expression of CD276, TNFSF4, PDCD1LG2, CD274, and TNFRSF9, and negatively correlated with the expression of CD40LG and TNFSF15. The scRNA-seq analysis showed that RORA and KLF10 were mainly expressed in natural killer cells. Conclusion The prognostic model based on seven feature circadian rhythm genes has certain predictive value for predicting survival of LUAD patients. Dysregulated expression of circadian genes may regulate the occurrence, progression as well as prognosis of LUAD through affecting TME, which provides a possible direction for finding potential strategies for treating LUAD from the perspective of mechanism by which circadian disorder affects immune cells.

OBJECTIVE To analyze the impact of the diagnosis-related groups （DRG） payment reform on the length of stay and medical costs in patients with chronic obstructive pulmonary disease （COPD） in Kashgar region， aiming to provide localized empirical evidence for the optimization of regional medical insurance payment methods. METHODS Based on the inpatient settlement database of the Xinjiang Uygur Autonomous Region Healthcare Security Administration， settlement data of COPD inpatients from 17 medical institutions in Kashgar region between January 1， 2022， and December 31， 2024， were extracted. The overall changes in patients’ length of stay and costs were compared before and after the reform. Subsequently， interrupted time series analysis （ITSA） was employed to explore the impact of the DRG payment reform on these variables. RESULTS Following the reform， both the average length of stay and various cost decreased significantly compared to the pre-reform period （ P ＜0.001）. At the overall sample level， the average length of stay， average total cost， average drug cost， average medical service cost， and average examination cost per admission all demonstrated significant long-term downward trends after the reform （ P ＜0.05）. However， the decrease in average out-of-pocket costs and the increase in average consumable costs per admission were not statistically significant （ P ＞0.05）. In tertiary medical institutions， the average length of stay and all categories of costs （except average consumable costs per admission） exhibited significant long-term upward trends after the reform （ P ＜0.05）； conversely， in secondary and lower-level medical institutions， the average length of stay， average total cost， average drug cost， average medical service cost， and average examination cost per admission showed significant long-term downward trends （ P ＜0.05）. CONCLUSIONS The DRG payment reform has achieved an overall effect of reducing the length of stay and controlling costs in COPD patients from Kashgar region. However， the effects vary across different levels of medical institutions： secondary and lower-level institutions show a long-term downward trend in length of stay and costs， whereas tertiary institutions exhibit a long-term upward trend. Furthermore， patients’ out-of-pocket financial burden does not show significant improvement.

Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

Introduction: Gender-affirming hormone therapy (GAHT) for transgender women utilizes estrogen and an anti-androgen like cyproterone acetate (CPA) which can both lead to hyperprolactinemia. Although mild prolactin elevations are common, the development of prolactinomas in transgender women on GAHT is rare. Case: A 23-year-old trans-woman on self-purchased estradiol hemihydrate (17β-estradiol) 4 mg and CPA 12.5 mg daily for GAHT presented with galactorrhea. Investigations revealed markedly elevated prolactin at 2,369 mIU/L and elevated estradiol at 848 pmol/L. A pituitary magnetic resonance imaging (MRI) identified a 0.4 × 0.5 cm microprolactinoma. She declined clinical advice to reduce her medication dose and continued on the same treatment. In the subsequent year, her peak prolactin was 1,383 mIU/L, and a repeat MRI showed the microprolactinoma remained stable. She continues to be on close clinical monitoring. Transgender females experience approximately a fourfold higher rate of developing prolactinomas. The patient’s choice to persist with GAHT reflects the challenges in managing gender dysphoria alongside medical complications. A recent paper by BJ Nolan et al. suggests using prolactin levels exceeding 2,000–3,000 mIU/L to guide further investigations including a pituitary MRI to rule out a prolactinoma. In most cases, the serum prolactin levels will return to the normal range with a reduction or discontinuation of the GAHT. Normalization of prolactin levels have been reported after gonadectomy and CPA cessation in transgender females on GAHT, which suggests that CPA usage may be associated with higher risk of hyperprolactinemia compared to estrogen therapy. Conclusion This case highlights that GAHT can lead to development of prolactinomas. Prolactin monitoring and MRI investigations should be reserved for symptomatic patients, and for those with significantly elevated or increasing prolactin levels. While treatment using dopamine agonists have been reported, this case demonstrates that conservative management and close monitoring can be a viable approach for structurally stable microprolactinomas.
Female ; Prolactinoma ; Transgender Persons

Introduction: Macro-thyroid-stimulating hormone (macro-TSH) is a rare complex formed by monomeric TSH with anti-TSH autoantibodies. Macromolecules of TSH are not renally excreted due to its large size, leading to elevated TSH measurements without clinical consequences. This rare condition frequently mimics subclinical hypothyroidism, often leading to misdiagnosis and inappropriate levothyroxine therapy. Case: A 17-year-old female with major depressive disorder was biochemically diagnosed with subclinical hypothyroidism (TSH 39.06 mIU/L, free thyroxine 4 12.9 pmol/L, antithyroid peroxidase negative) and commenced on levothyroxine. Over 5 years, her TSH levels heavily fluctuated (0.48–82.59 mIU/L) and remained persistently elevated with high-normal free T4 levels despite treatment adherence. An endocrinology consult was obtained, and clinical evaluation revealed a clinically asymptomatic and euthyroid patient, with no family history of thyroid disease or supplement use, and there was no goiter. Assay interference was excluded by analyzing her thyroid function tests on a different platform, which yielded similar biochemical results. Subsequently, a polyethylene glycol (PEG) precipitation test was performed. Her pre-PEG TSH of 29.24 mIU/L decreased significantly to 2.78 mIU/L post-PEG. This yielded a remarkably low TSH recovery rate of 9.5%, strongly indicating the presence of macroTSH. Levothyroxine was then stopped, and she remained clinically euthyroid. Conclusion While gel filtration chromatography remains the gold standard for diagnosing this condition, PEG precipitation is a more accessible, cost-effective, and reliable screening method in clinical practice. A TSH recovery rate below 20% is considered highly suggestive of macro-TSH. Clinicians should maintain a high index of suspicion for macro-TSH in asymptomatic patients presenting with isolated TSH elevations that do not respond to thyroxine therapy. Prompt recognition prevents misdiagnosis and avoids the potential risks of unnecessary thyroid hormone replacement.
Hypothyroidism ; Thyrotropin

To explore the clinical significance of decreased serum immunoglobulin (Ig) A levels in patients with IgG4-related disease (IgG4-RD).

Objective To explore the effect and mechanism of Gegen Qinlian decoction (GQD) on myocardial injury induced by high-fat diet combined with streptozotocin in type 2 diabetic mice through network pharmacology and animal experiments. MethodsNetwork pharmacology was applied to screen the potential signaling pathways of GQD in the intervention of diabetic heart disease (DHD). A total of 36 specific pathogen-free (SPF) male C57BL/6J mice aged 8 weeks were acclimatized for 1 week and randomly divided into a normal control group (n=6) and a model group (n=30). Mice in the model group were fed a 60% high-fat diet and 5% glucose water for 4 weeks, and were intraperitoneally injected with 100 mg/kg streptozotocin after 12 h of fasting to establish the type 2 diabetes model. Mice in the normal control group were given a conventional diet and drinking water, and were intraperitoneally injected with an equal volume of citrate buffer after 12 h of fasting at the same time point. After successful establishment of the diabetic mouse model, the model mice were randomly divided into five groups according to body weight: model control group, GQD low-dose group, GQD medium-dose group, GQD high-dose group, and metformin positive control group, with 6 mice in each group. After 6 weeks of intragastric administration of corresponding doses of GQD, metformin, and ddH₂O respectively, all mice in the six groups (one normal control group and five model groups) were anesthetized with inhaled 2% isoflurane, blood samples were collected via eyeball enucleation, and heart tissues were harvested after euthanasia by cardiac exsanguination. Hematoxylin-eosin (HE) staining and wheat germ agglutinin (WGA) staining were performed to observe the pathological damage of myocardial tissues and measure the cross-sectional area of cardiomyocytes. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of pro-inflammatory cytokines in serum. Immunohistochemical staining was adopted to determine the protein expression levels of receptor for advanced glycation end products (RAGE), nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), and phosphorylated nuclear factor-κB p65 (p-p65) in myocardial tissues. ResultsNetwork pharmacology analysis revealed that the targets of GQD against DHD were significantly enriched in inflammatory pathways, including the advanced glycation end products (AGEs)-RAGE axis, tumor necrosis factor (TNF) and interleukin-17 (IL-17) signaling pathways. HE and WGA staining results showed that, compared with the normal control group, the model control group exhibited myocardial fiber rupture, cardiomyocyte swelling, and significantly increased cardiomyocyte cross-sectional area (P<0.05). Compared with the model control group, GQD intervention significantly ameliorated the pathological changes, including myocardial fiber rupture, cell swelling, and cardiomyocyte hypertrophy. The results of immunohistochemical staining and ELISA indicated that compared with the model control group, GQD intervention markedly downregulated the protein expression of RAGE, NLRP3, and p-p65 in myocardial tissues, as well as the levels of serum pro-inflammatory cytokines (P<0.05). ConclusionGQD can effectively alleviate myocardial pathological injury in diet-induced type 2 diabetic mice, and its mechanism may be related to inhibiting the activation of the RAGE/p-p65/NLRP3 signaling pathway and reducing myocardial inflammatory response.

With the rapid advancement of artificial intelligence technology, chatbots have shown great potential in the healthcare sector. From personalized health advice to chronic disease management and psychological support, chatbots have demonstrated significant advantages in improving the efficiency and quality of healthcare services. As the scope of their applications expands, the relationship between technological complexity and practical application scenarios has become increasingly intertwined, necessitating a more comprehensive evaluation of both aspects. This paper, from the perspective of he althcare applications, systematically reviews the technological pathways and development of chatbots in the medical field, providing an in-depth analysis of their performance across various medical scenarios. It thoroughly examines the advantages and limitations of chatbots, aiming to offer theoretical support for future research and propose feasible recommendations for the broader adoption of chatbot technologies in healthcare.