Strabismus, a common ocular condition, arises from an imbalance in the extraocular muscle force and deviation of the visual axis due to various factors. Concomitant strabismus is the predominant form of exotropia, with its pathogenesis believed to be associated with hereditary factors, abnormal eye accommodation function, and anomalies in binocular anatomy. Surgical intervention is often necessary for aligning the visual axes of both eyes and facilitating the recovery and establishment of stereoscopic vision. Despite this, the etiology of concomitant exotropia remains incompletely understood. This review consolidates recent research on aberrant molecular expression and pathological morphological changes within extraocular muscles affected by concomitant exotropia, offering insights into disease causation at molecular and pathological levels to underpin future preventive measures and clinical interventions. The discussion encompasses histological changes observed under electron microscopy as well as the impact of heavy chain protein, satellite cells, cadherin, growth factors on extraocular muscle protein expression.

Myeloid-derived cells (MDCs) are crucial in immune response and tissue homeostasis. They have high functional plasticity and can be polarized according to microenvironment signals. These cells, including macrophages, neutrophils, and dendritic cells (DCs), exhibit different functional polarization states in different pathological environments and are involved in the occurrence and development of diseases such as inflammation and tumors. Studies have shown that metabolic reprogramming plays a key role in the functional polarization of MDCs, affecting the cellular energy supply and regulating immune function. This paper reviews classification, function and polarization mechanism of MDCs and discusses metabolic reprogramming. In addition, the therapeutic strategies targeting MDC are summarized, which is expected to provide new targets for tumor immunotherapy.
Humans ; Tumor Microenvironment/immunology* ; Myeloid Cells/metabolism* ; Neoplasms/pathology* ; Animals ; Immunotherapy/methods* ; Dendritic Cells/immunology* ; Macrophages/immunology*

Objective Hypobaric chamber and simulated weightless bed are essential methods for aerospace medical research,and conducting state assessment of volunteers before and after hypobaric chamber and simulated weightless bed tests is an essential guideline for aerospace implementation medicine.To further improve the efficiency of human condition assessment,in addition to the conventional biochemical and physiological indicators,the human oral exhaled gas can be used for condition assessment,and the olfactometry acquisition equipment and analysis software can collect and detect most volatile gases to complete the human oral exhaled gas data acquisition.Conducting comparative analysis of olfactory mapping data from different populations may be a means to assess the status of the body.Methods The olfactometry acquisition equipment was used to collect the oral exhaled breath olfactometry profiles of the general population,hypobaric cabin volunteers,and ambulatory volunteers.The olfactometry analysis software was used to calculate the 12 eigenvalues of the olfactometry profiles and the t-SNE downscaling,and the radar plots were used to analyze the olfactometry profiles of the general population,low-pressure cabin volunteers,and ambulatory volunteers respectively.A comparative analysis of different populations was conducted.Results(1)The t-SNE mapping data of the general population and the ambulatory volunteers were almost indistinguishable;(2)the t-SNE mapping data of the hypobaric cabin volunteers and the general population had a slight overlap,but the distinguishability of the vast majority of the t-SNE mapping data was obvious;(3)the t-SNE mapping data of the hypobaric cabin volunteers and the ambulatory volunteers were distinguishable with no overlap,and the ambulatory t SNE data are highly aggregated,and the distribution of t-SNE data in low-pressure cabin is more discrete;(4)there are 2-3 sensors with large eigenvalues and a large range of variation for both low-pressure cabin volunteers and recumbent volunteers after training activities,and the common sensor with a large range of variation is S6.Conclusion Olfactory diagnostic analysis mapping may be a means to assess the health status of the body and may be useful for spaceflight health status assessment in the future.The analysis and application of flight health state assessment can be a reference in the future.

Objective To study the effect of practicing traditional Chinese medicine(TCM)guidance on the health in weightless conditions based on the examination results of the TCM diagnostic instrument.Methods 6 subjects in weightless conditions practiced TCM guidance for 14 consecutive days,once a day for 8 minutes each time.The Digital TCM Diagnostic Instrument and TCM Syndrome Diagnosis Scale were used to collect information before and after their practice of TCM guidance through diagnostic methods of observation,palpation and inquiry according to TCM theory.The data such as the degree of virtual-reality,pulse rate,and characteristic parameters of pulse diagrams h3/h1,h4/h1,t1,h1/t1 were processed and analyzed,and the changes before and after the practice were compared.Results Compared with before the practice,the degree of deficiency syndrome was significantly reduced after practicing TCM guidance(P<0.05),the pulse rate was significantly decreased(P<0.01),and the pulse diagnosis parameters h3/h1 and t1 were significantly decreased(P<0.05),while h4/h1 and h1/t1 showed no significant changes.Conclusion Practicing TCM guidance in weightless conditions is helpful for enhance cardiovascular regulatory function,correcting symptom bias,adjusting the body's balance state,and has a positive effect on health.

ObjectiveTo explore the underlying mechanism by which the Chinese medicine compound Yitangkang granule（YTK） treats diabetic kidney disease （DKD） by observing its effects on podocyte autophagy through the regulation of phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/forkhead transcription factor O1 （FoxO1） signaling pathway mediated by silent information regulator 1 （SIRT1） via advanced glycation end products （AGE）/receptor for AGE （RAGE） axis. MethodNinety-six 8-week-old healthy male SPF-grade Wistar rats were selected and randomly divided into blank control group （B）， model control group， high-dose YTK （40 g·kg^-1）， medium-dose YTK （20 g·kg^-1）， low-dose YTK （10 g·kg^-1）， and Western medicine control （20 mg·kg^-1 losartan） groups. The DKD rat model was established by high-fat diet feeding combined with intraperitoneal injection of streptozotocin. After successful modeling， the rats in each group received the corresponding treatments for eight weeks. The levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， and catalase （CAT） were measured according to the instructions of the respective assay kits. Hematoxylin and eosin （HE） staining was used to observe pathological changes in kidney tissues. Immunohistochemistry was employed to detect the average optical density values of α-smooth muscle actin （α-SMA）， fibronectin （FN）， desmin， and nephrin. Western blot analysis was used to measure the expression levels of PI3K， phosphorylated PI3K （p-PI3K）， Akt， phosphorylated Akt （p-Akt）， RAGE， SIRT1， Caspase-3， and FoxO1 proteins in kidney tissues of DKD rats. ResultCompared with the blank control group， the model group showed significantly lower levels of SOD， GSH-Px， and CAT， and significantly higher levels of MDA （P<0.01）. The rats exhibited severe kidney damage. The positive expression of podocyte marker proteins α-SMA， FN， and desmin increased significantly， while nephrin and podocin significantly decreased （P<0.01）. The expression levels of PI3K， p-PI3K， Akt， p-Akt， RAGE， and Caspase-3 proteins were significantly elevated， while SIRT1 and FoxO1 protein levels were significantly reduced （P<0.01）. Compared with the model control group， rats in the YTK treatment groups showed significantly higher levels of SOD， GSH-Px， and CAT， and significantly lower levels of MDA in serum （P<0.01）. The degree of kidney damage was reduced to varying extents. The average optical density values of podocyte marker proteins α-SMA， FN， and desmin were significantly decreased， while nephrin and podocin significantly increased （P<0.01）. The expression levels of PI3K， p-PI3K， Akt， p-Akt， RAGE， and Caspase-3 in kidney tissues were significantly reduced， while SIRT1 and FoxO1 expression levels significantly increased （P<0.01）. The Chinese medicine groups demonstrated a clear dose-response trend. ConclusionYTK may alleviate kidney pathological damage， reduce proteinuria， and protect kidney function in DKD rats， thereby delaying the progression of DKD by improving podocyte autophagy through the AGE-RAGE axis-mediated SIRT1 regulation of the PI3K/Akt/FoxO1 signaling pathway. Additionally， a dose-response relationship was observed in the Chinese medicine groups.

ObjectiveTo investigate the correlation between mild cognitive impairment (MCI) and traditional Chinese medicine (TCM) body constitution types in the elderly, and to provide an evidence for the control of cognitive impairment in the elderly. MethodsThe elderly aged 65 and above who participated in the community physical examinations in a community of Changning District, Shanghai were selected as the research subjects. The cognitive function was assessed by using the Clock Drawing Test combined with the Ascertain Dementia 8-item Questionnaire (AD8), the Montreal Cognitive Assessment (MoCA) and the Mini-mental State Examination (MMSE). The diagnostic criteria for MCI was identified based on the 2018 Chinese Guidelines for the Diagnosis and Treatment of Dementia and Cognitive Disorders, along with the assessment results and clinical history information. The current investigation method was used to collect the basic information and the prevalence of chronic disease of the subjects through questionnaire inquiries. The elderly subjects’ ability to take care of themselves was evaluated based on the Elderly Self⁃Care Ability Evaluation Scale, while the TCM body constitution types were determined based on the Chinese Medicine Health Care Management Service Specification. The association of the detection rate of MCI with gender, education level, history of chronic disease and TCM body constitution types were analyzed lastly. ResultsA total of 2 351 elderly people were investigated, including 1 037 males and 1 314 females, with an average age of (74.11±6.15) years. 174 subjects, accounting for 7.40%, were identified with MCI. The highest detection rate of MCI in the elderly are those with a Qi stagnation constitution (10.8%), followed by those with a dampness-heat constitution (9.1%) and a Qi deficiency constitution (8.4%). Multivariate logistic regression analysis showed that advanced age, lower educational level, a history of tuberculosis, and TCM constitutions such as dampness-heat, Qi stagnation, and Qi deficiency were the potential risk factors for MCI. ConclusionThere is a significant association between TCM constitution types such as dampness-heat, Qi stagnation, and Qi deficiency with MCI. TCM techniques can be integrated into the health management services for the elderly population, and targeted interventions can be provided to those with imbalanced constitution types so as to reduce the risk of MCI.

A purified polysaccharide with a galactose backbone(SPR-1,Mw 3,622 Da)was isolated from processed Polygonati Rhizoma with black beans(PRWB)and characterized its chemical properties.The backbone of SPR-1 consisted of[(4)-β-D-Galp-(1]9→ 4,6)-β-D-Galp-(1 → 4)-α-D-GalpA-(1 → 4)-α-D-GalpA-(1 →4)-α-D-Glcp-(1 → 4,6)-α-D-Glcp-(1 → 4)-α/β-D-Glcp,with a branch chain of R1:β-D-Galp-(1 → 3)-β-D-Galp-(1 → connected to the →4,6)-β-D-Galp-(1 → via O-6,and a branch chain of R2:α-D-Glcp-(1 →6)-α-D-Glcp-(1 → connected to the →4,6)-α-D-Glcp-(1 → via O-6.Immunomodulatory assays showed that the SPR-1 significantly activated macrophages,and increased secretion of NO and cytokines(i.e.,IL-1β and TNF-α),as well as promoted the phagocytic activities of cells.Furthermore,isothermal titration calorimetry(ITC)analysis and molecular docking results indicated high-affinity binding between SPR-1 and MD2 with the equilibrium dissociation constant(KD)of 18.8 μM.It was suggested that SPR-1 activated the immune response through Toll-like receptor 4(TLR4)signaling and downstream responses.Our research demon-strated that the SPR-1 has a promising candidate from PRWB for the TLR4 agonist to induce immune response,and also provided an easily accessible way that can be used for PR deep processing.

Background/Aims: Hepatitis B virus (HBV)-DNA integration in HBV-related hepatocellular carcinoma (HBV-HCC) can be targeted by HBV-specific T cells. SCG101 is an autologous, HBV-specific T-cell product expressing a T-cell receptor (TCR) after lentiviral transduction recognizing the envelope-derived peptide (S20-28) on HLA-A2. We here validated its safety and efficacy preclinically and applied it to an HBV-related HCC patient (NCT05339321). Methods: Good Manufacturing Practice-grade manufactured cells were assessed for off-target reactivity and functionality against hepatoma cells. Subsequently, a patient with advanced HBV-HCC (Child-Pugh class A, Barcelona Clinic Liver Cancer stage B, Eastern Cooperative Oncology Group performance status 0, hepatitis B e antigen-, serum hepatitis B surface antigen [HBsAg]+, HBsAg+ hepatocytes 10%) received 7.9×107 cells/kg after lymphodepletion. Safety, T-cell persistence, and antiviral and antitumor efficacy were evaluated. Results: SCG101, produced at high numbers in a closed-bag system, showed HBV-specific functionality against HBV-HCC cells in vitro and in vivo. Clinically, treatment was well tolerated, and all adverse events, including transient hepatic damage, were reversible. On day 3, ALT levels increased to 1,404 U/L, and concurrently, serum HBsAg started decreasing by 3.84 log10 and remained <1 IU/mL for over six months. HBsAg-expressing hepatocytes in liver biopsies were undetectable after 73 days. The patient achieved a partial response according to modified RECIST with a >70% reduction in target lesion size. Transferred T cells expanded, developed a stem cell-like memory phenotype, and were still detectable after six months in the patient’s blood. Conclusions SCG101 T-cell therapy showed encouraging efficacy and safety in preclinical models and in a patient with primary HBV-HCC and concomitant chronic hepatitis B with the capability to eliminate HBsAg+ cells and achieve sustained tumor control after single dosing.

Background: Insulin resistance (IR) is the key pathological basis of many metabolic disorders. Lack of asialoglycoprotein receptor 1 (ASGR1) decreased the serum lipid levels and reduced the risk of coronary artery disease. However, whether ASGR1 also participates in the regulatory network of insulin sensitivity and glucose metabolism remains unknown. Methods: The constructed ASGR1 knockout mice and ASGR1-/- HepG2 cell lines were used to establish the animal model of metabolic syndrome and the IR cell model by high-fat diet (HFD) or drug induction, respectively. Then we evaluated the glucose metabolism and insulin signaling in vivo and in vitro. Results: ASGR1 deficiency ameliorated systemic IR in mice fed with HFD, evidenced by improved insulin intolerance, serum insulin, and homeostasis model assessment of IR index, mainly contributed from increased insulin signaling in the liver, but not in muscle or adipose tissues. Meanwhile, the insulin signal transduction was significantly enhanced in ASGR1-/- HepG2 cells. By transcriptome analyses and comparison, those differentially expressed genes between ASGR1 null and wild type were enriched in the insulin signal pathway, particularly in phosphoinositide 3-kinase-AKT signaling. Notably, ASGR1 deficiency significantly reduced hepatic gluconeogenesis and glycogenolysis. Conclusion The ASGR1 deficiency was consequentially linked with improved hepatic insulin sensitivity under metabolic stress, hepatic IR was the core factor of systemic IR, and overcoming hepatic IR significantly relieved the systemic IR. It suggests that ASGR1 is a potential intervention target for improving systemic IR in metabolic disorders.

OBJECTIVE: To study the chemical constituents from the roots of Curcuma longa. METHODS: The structures of the compounds were elucidated based on extensive spectral analysis, including 1D and 2D NMR, MS, UV, and CD analysis. RESULTS: Two new sesquiterpene compounds (1S,2R,5R,7S,8R)-2,8-epoxy-5-hydroxybisabola-3,10-dioen-9-one ( 1), (1R,2R,5R,7S,8R)-2,8-epoxy-5-hydroxybisabola-3,10-dioen-9-one ( 2), and a new natural product 6-(4-Hydroxymethylphenyl)-2-methyl-hept-2-ene-4-one ( 3) together with three known compounds ar-turmerone ( 4), 2-methyl-6-(4-hydroxyphenyl-3-methyl)-2-hepten-4-one ( 5) and 2-methyl-6-(4-hydroxyphenyl)-2-hepten-4-one ( 6) were isolated from C. longa root extract with 95% ethanol. CONCLUSION In the study, three new compounds were isolated from C. longa, and their absolute configurations were determined.