ObjectiveTo investigate the role of paraventricular nucleus (PVN) corticotropin releasing hormone (CRH) neurons in chronic restraint stress (CRS)-induced anxiety-like behavior. And whether exercise relieves chronic restraint stress-induced anxiety through PVN CRH neurons. MethodsTwenty 8-week-old male C57BL/6J mice were randomly divided into control (Ctrl) group and chronic restraint stress (CRS) group. The open field test (OFT) and elevated plus maze (EPM) were used to evaluate anxiety-like behavior of the mice. Food intake was recorded after CRS. Immunofluorescence staining was used to label the expression of c-Fos expression in PVN and calculate the co-expression of c-Fos and CRH neurons. We used chemogenetic activation of PVN CRH neurons to observed the anxiety-like behavior. 8-week treadmill training (10-16 m/min, 60 min/d, 6 d/week) were used to explore the role of exercise in ameliorating CRS-induced anxiety behavior and how PVN CRH neurons involved in it. ResultsCompared with Ctrl group, CRS group exhibited significant anxiety-like behavior. In OFT, the mice in CRS groups spent less time in center area (P<0.001). In EPM, the time in open arm in CRS group were significantly decreased (P<0.001). Besides, food intake was also suppressed in CRS group compared with Ctrl group (P<0.05). Compared with Ctrl group, CRS significantly increase c-Fos expression in PVN and most of CRH neurons co-express c-Fos (P<0.001). Chemogenetic activation of PVN CRH neurons induced anxiety-like behavior (P<0.05) and inhibited feeding behavior (P<0.01). Exercise relieves chronic restraint stress-induced anxiety (P<0.001) and relieved the anorexia caused by chronic restraint stress (P<0.05). Aerobic exercise inhibited the CRS labeled c-Fos in PVN CRH neurons (P<0.001). Furthermore, ablation of PVN CRH neurons attenuated CRS induced anxiety-like behavior. ConclusionCRS activated PVN CRH neurons, induced anxiety-like behavior and reduced food intake. 8-week exercise attenuated CRS-induced anxiety-like behavior through inhibiting PVN CRH neuron. Ablation of CRH PVN neurons ameliorated CRS-induced anxiety-like behavior. These finding reveals a potential neural mechanism of exercise-relieving CRS-induced anxiety-like behavior. This provides a new idea and theoretical basis for the treatment of anxiety and related mental disorders.

Panvascular disease， with vascular diseases as the common pathological feature， is mainly manifested as atherosclerosis. Panvascular disease mainly affects the important organs of the heart， brain， kidney， and limbs. It is one of the leading causes of death for Chinese residents at present. Previously， due to the narrow branches of disciplines， too much attention was paid to local lesions， resulting in the neglect of panvascular disease as a systemic one. The fact that panvascular disease has overall pathology and comprehensive and individualized treatment strategies， makes the disease highly compatible with the principles of holism concept and syndrome differentiation and treatment in traditional Chinese medicine （TCM）. It is believed that blood stasis is the core pathogenesis of atherosclerosis and is involved in the whole process of atherosclerosis. The theories of ''blood vessel''， ''meridians''， ''visceral manifestation''， and ''organs-meridians'' in TCM are helpful to comprehensively understand the complexity of panvascular diseases. Moreover， those theories can provide systematic treatment strategies. The TCM syndromes of panvascular diseases evolve from ''phlegm， stasis， stagnation， and deficiency''. Panvascular arteriosclerosis is related to the syndrome of ''stasis and phlegm''， and the treatment mainly promotes blood circulation and removes phlegm. There are different specific drugs and mechanisms of action for coronary atherosclerosis， cerebral atherosclerosis， and renal artery atherosclerotic stenosis. Panvascular venous lesions are related to the syndrome of ''deficiency and stasis'' in TCM， and the TCM treatment mainly invigorates Qi and promotes blood circulation， which can inhibit venous thrombosis， improve venous ulcers， and resist venous endothelial damage. Panvascular microcirculatory lesions are inseparable from the ''stagnation and stasis'' in TCM， and the treatment mainly promotes Qi and dredges collaterals， which has a good effect on coronary microvascular lesions， diabetic microvascular lesions， pulmonary microvascular lesions， and pancreatic microvascular lesions. Panvascular lymphatic lesions are related to the syndrome of ''water and stasis'' in TCM. The treatment method focuses on promoting blood circulation and water excretion， which can promote lymphangiogenesis and enhance lymphatic reflux. In addition， the combination of TCM and modern technology， especially the application of artificial intelligence， can improve the efficiency of early identification and personalized treatment， resulting in early screening and comprehensive management of panvascular diseases. Therefore， TCM will play a vital role in the prevention and treatment of panvascular diseases.

Panvascular disease， with vascular diseases as the common pathological feature， is mainly manifested as atherosclerosis. Panvascular disease mainly affects the important organs of the heart， brain， kidney， and limbs. It is one of the leading causes of death for Chinese residents at present. Previously， due to the narrow branches of disciplines， too much attention was paid to local lesions， resulting in the neglect of panvascular disease as a systemic one. The fact that panvascular disease has overall pathology and comprehensive and individualized treatment strategies， makes the disease highly compatible with the principles of holism concept and syndrome differentiation and treatment in traditional Chinese medicine （TCM）. It is believed that blood stasis is the core pathogenesis of atherosclerosis and is involved in the whole process of atherosclerosis. The theories of ''blood vessel''， ''meridians''， ''visceral manifestation''， and ''organs-meridians'' in TCM are helpful to comprehensively understand the complexity of panvascular diseases. Moreover， those theories can provide systematic treatment strategies. The TCM syndromes of panvascular diseases evolve from ''phlegm， stasis， stagnation， and deficiency''. Panvascular arteriosclerosis is related to the syndrome of ''stasis and phlegm''， and the treatment mainly promotes blood circulation and removes phlegm. There are different specific drugs and mechanisms of action for coronary atherosclerosis， cerebral atherosclerosis， and renal artery atherosclerotic stenosis. Panvascular venous lesions are related to the syndrome of ''deficiency and stasis'' in TCM， and the TCM treatment mainly invigorates Qi and promotes blood circulation， which can inhibit venous thrombosis， improve venous ulcers， and resist venous endothelial damage. Panvascular microcirculatory lesions are inseparable from the ''stagnation and stasis'' in TCM， and the treatment mainly promotes Qi and dredges collaterals， which has a good effect on coronary microvascular lesions， diabetic microvascular lesions， pulmonary microvascular lesions， and pancreatic microvascular lesions. Panvascular lymphatic lesions are related to the syndrome of ''water and stasis'' in TCM. The treatment method focuses on promoting blood circulation and water excretion， which can promote lymphangiogenesis and enhance lymphatic reflux. In addition， the combination of TCM and modern technology， especially the application of artificial intelligence， can improve the efficiency of early identification and personalized treatment， resulting in early screening and comprehensive management of panvascular diseases. Therefore， TCM will play a vital role in the prevention and treatment of panvascular diseases.

AIM:To investigate the value of optical coherence tomography angiography(OCTA)indicators in the diagnosis of diabetic retinopathy(DR), and to provide patients with diabetic nephropathy(DN)with more sensitive OCTA screening indicators to detect concurrent DR at an early stage.METHODS: A total of 200 patients who treated in the ophthalmology department of the Seventh Affiliated Hospital, Sun Yat-sen University from 2022 to 2023 were included, including 95 first-diagnosed DR patients and 105 patients without DR, and all patients underwent OCTA examination and a collection of demographics and renal function parameters. After a quality check, automated measurements of the foveal avascular zone area, vessel density(VD), and perfusion density(PD)of both 3 mm×3 mm and 6 mm×6 mm windows were obtained.RESULTS: Using random forest and multivariate Logistic regression methods, we developed a diagnostic model for DR based on 12 variables(age, FBG, SBP, DBP, HbA1c, ALT, ALP, urea/Scr, DM duration, HUA, DN, and CMT). Adding specific OCTA parameters enhanced the efficacy of the existing diagnostic model for DR(outer vessel density in 6 mm×6 mm window, AUC=0.837 vs 0.819, P=0.03). In the study of DN patients, the parameters in the 6 mm×6 mm window improved the diagnostic efficacy of DR(inner VD; outer VD; full VD; outer PD; full PD).CONCLUSION:The outer VD in the 6 mm×6 mm window can enhance the efficacy of the traditional DR diagnostic model. Meanwhile, compared with the 3 mm×3 mm window, the microvascular parameters in the 6 mm× 6 mm window focusing on DN patients can be more sensitive to diagnosing the occurrence of DR.

AIM: To screen and analyze the influencing factors of myopia among primary and secondary school students and establish a predictive model to provide ideas for the prevention and control measures of myopia among children and adolescents.METHODS:A total of 1 759 primary and secondary school students from 2 primary schools, 2 junior high schools, 2 senior high schools and 1 vocational high school in the urban area of Qingdao were sampled by means of stratified cluster sampling in September 2023. Vision screening and a questionnaire survey on influencing factors were carried out based on machine learning algorithms. The screening and determination were mainly conducted in accordance with the Standard Logarithmic Visual Acuity Chart(GB/T11533-2011)and the Specifications for Screening Myopia in Children and Adolescents. The influencing factors of myopia were analyzed and a prediction model was developed based on the machine learning algorithms LASSO in combination with XGBoost, and visualization was achieved through an interactive Nomogram. Statistical analysis was performed using R statistical software version 4.3.3.RESULTS:The screening prevalence of myopia among primary and secondary school students in the urban area of Qingdao was 70.61%(1 242 cases). The optimal predictive variables for screening were grade, gender, whether parents were myopic, daily indoor sedentary time, appropriate distance between eyes and books during reading and writing, daily sleep time, distance between eyes and TV screen when watching TV/playing video games exceeding 3 meters, the playground during breaks, total duration of tutorial classes, how often eyes are rested during near work, daily computer usage time, and average daily homework time after school, totaling 12 influencing factors. The AUCs of the training set and test set were 0.770(95%CI:0.751-0.789)and 0.732(95%CI:0.714-0.750), respectively.CONCLUSION: A machine learning-based prediction model was developed and validated to predict the risk of myopia onset in primary and secondary school students, accompanied by effective visualization techniques.

[Objective] To establish a new scoring system to predict the perioperative outcomes (operation time, intraoperative blood loss, and trifecta achievement) in patients undergoing robot-assisted partial nephrectomy (RAPN) by integrating the RENAL and Mayo adhesive probability (MAP) scores. [Methods] Clinical data of 178 patients with renal cell carcinoma who underwent RAPN performed by the same surgeon in our hospital during Jan.2015 and Jan.2022 were retrospectively analyzed.The RENAL and MAP scores of all patients were calculated.Linear regression and logistic regression were used to evaluate the associations between the components of the RENAL and MAP scores (a total of 6 variables) and perioperative outcomes.The factors with significant associations were then included into logistic regression analysis to identify independent predictors for constructing an assessment system for perioperative outcomes, and the receiver operating characteristic (ROC) curve was plotted to calculate the area under the curve (AUC) to predict its efficacy. [Results] Multivariate linear regression analysis showed that tumor size (β=6.14, 95%CI: 1.93—10.34, P=0.004), exophytic rate (β=10.60, 95%CI: 3.44—17.76, P=0.004), and perinephric fat thickness (β=16.48, 95%CI: 8.52—24.45, P<0.001) were significantly associated with operation time.Tumor size (β=10.55 95%CI: 5.60—15.49, P<0.001) was associated with both intraoperative blood loss and trifecta achievement (OR=1.73, 95%CI: 1.26—2.36, P=0.001). Multivariate logistic regression analysis of these 3 factors identified tumor size (OR=9.07, 95% CI: 1.18—69.45, P=0.03) and perinephric fat thickness (OR=2.28, 95%CI: 1.86—6.04, P=0.01) as independent predictors of perioperative outcomes.Based on these findings, the tumor size and perinephric fat thickness (RP) scoring was constructed, which demonstrated better predictive ability than RENAL score or MAP score alone (RP vs.RENAL vs.MAP: 0.766 vs.0.548 vs.0.684). [Conclusion] The RP score includes fewer variables than the RENAL and MAP scores but outperforms them.

BACKGROUND:The decreased postural control ability due to mild cognitive impairment in elderly people leads to the increased risk of falls.Dual-task is the primary research paradigm for evaluating the relationship between cognition and postural control in the scenes close to real life.The sample entropy of the plantar center of pressure(COP)displacement during standing can represent the complexity of postural control. OBJECTIVE:Based on the COP displacement sample entropy,to analyze the differences in postural stability characteristics and control strategies between older adults with mild cognitive impairment and cognitively normal older adults during the dual-task with postural control and spatial working memory,aiming to explore the impact of cognitive impairment on the postural control ability during standing. METHODS:Sixteen older adults with mild cognitive impairment and 17 cognitively normal older adults were eligible and selected for the study.They completed five test tasks,including spatial working memory,double-feet balance stance,Romberg stance,double-feet balance stance-spatial working memory dual-task,and Romberg stance-spatial working memory dual-task,with three valid completions of each task.The plantar COP data were collected by the Kistler 3D force platform.The indicators included cognitive behavior(cognitive score and reaction time)and kinematic indexes(COP displacement and sample entropy). RESULTS AND CONCLUSION:The older adults with mild cognitive impairment performed the spatial working memory task with the greatest cognitive score and the shortest reaction time,the double-feet balance stance-spatial working memory dual-task with moderate cognitive score and reaction time,and the Romberg stance-spatial working memory dual-task with the smallest cognitive score and the longest reaction time,where the differences were significant among the tasks(P<0.05).In the older adults with mild cognitive impairment,the anterior-posterior and medial-lateral COP displacements were significantly greater,and their sample entropy values were significantly smaller in the double-feet balance stance-spatial working memory dual-task and Romberg stance-spatial working memory dual-task than in the double-feet balance stance and Romberg stance tasks(P<0.05).In the spatial working memory task,there were no significant differences in cognitive score and reaction time between the both groups(P>0.05);however,in the double-feet balance stance-spatial working memory dual-task and Romberg stance-spatial working memory dual-task,cognitive scores were significantly smaller and reaction times were longer in the older adults with mild cognitive impairment compared with the cognitively normal older adults(P<0.05).In the double-feet balance stance-spatial working memory dual-task and Romberg stance-spatial working memory dual-task,the older adults with mild cognitive impairment exhibited significantly greater anterior-posterior and medial-lateral COP displacements and significantly smaller sample entropy values compared with the cognitively normal older adults(P<0.05).All findings indicate that compared with cognitively normal older adults,older adults with mild cognitive impairment exhibit smaller complexity,poorer systematic adaption and decreased automatic regulation of the postural control during performing the dual-tasks,who are more susceptible to spatial working memory interference,leading to the increased risk of falls.

Background: Diabetic nephropathy (DN) is the most common and serious complication of diabetes mellitus. Shionone (SH), an important triterpenoid compound in the root extract of Aster, might exert a protective effect in DN mice and high glucose cultivated glomerular podocytes. The current study aimed to unravel the underlying mechanism by which SH mitigates DN. We postulate that SH stimulates the expression of sestrin-2 (SESN2), a pivotal stress-inducible protein in the anti-inflammasome machinery. Methods: We utilized high-fat diet combined with streptozotocin (55 mg/kg intraperitoneal) for DN mice model, and high glucose (30 mM, 48 hours) cultured glomerular podocytes for DN cell model to evaluate the effect of SH. We also preformed experimentation on SESN2 deficiency models (SESN2 knockout mice and SESN2 siRNA in cells) to further prove our hypothesis. Results: The results demonstrated that SH effectively suppressed glomerular fibrosis, induced adenosine monophosphate-activated protein kinase (AMPK) phosphorylation, and inhibited NLR family pyrin domain containing 3 (NLRP3) activation. Furthermore, our findings revealed that SH exerted its anti-inflammatory effect through Sesn2-dependent nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation and subsequent activation of its downstream target heme oxygenase-1 (HO-1). Conclusion In summary, our findings suggest that SH serves as a promising therapeutic agent for the treatment of DN-related glomerular fibrosis. SH enhances the expression of SESN2, attenuates α-smooth muscle actin accumulation, and suppresses NLRP3-related inflammation through the Nrf2/HO-1 signaling pathway.

BACKGROUND:The imbalance between bone resorption and bone formation in microgravity environments leads to significant bone loss in astronauts.Current research indicates that bone loss under microgravity conditions is the result of the combined effects of various cells,tissues,and systems. OBJECTIVE:To review different biological effects of microgravity on various cells,tissues,or systems,and summarize the mechanisms by which microgravity leads to the development of osteoporosis. METHODS:Databases such as PubMed,Web of Science,and the Cochrane Database were searched for relevant literature from 2000 to 2023.The inclusion criteria were all articles related to tissue engineering studies and basic research on osteoporosis caused by microgravity.Ultimately,85 articles were included for review. RESULTS AND CONCLUSION:(1)In microgravity environment,bone marrow mesenchymal stem cells tend to differentiate more into adipocytes rather than osteoblasts,and hematopoietic stem cells in this environment are more inclined to differentiate into osteoclasts,reducing differentiation into the erythroid lineage.At the same time,microgravity inhibits the proliferation and differentiation of osteoblasts,promotes apoptosis of osteoblasts,alters cell morphology,and reduces the mineralization capacity of osteoblasts.Microgravity significantly increases the number and activity of osteoclasts.Microgravity also hinders the differentiation of osteoblasts into osteocytes and promotes the apoptosis of osteocytes.(2)In a microgravity environment,the body experiences changes such as skeletal muscle atrophy,microvascular remodeling,bone microcirculation disorders,and endocrine disruption.These changes lead to mechanical unloading in the bone microenvironment,insufficient blood perfusion,and calcium cycle disorders,which significantly impact the development of osteoporosis.(3)At present,the mechanism by which microgravity causes osteoporosis is relatively complex.A deeper study of these physiological mechanisms is crucial to ensuring the health of astronauts during long-term space missions,and provides a theoretical basis for the prevention and treatment of osteoporosis.

Abstract Postoperative urinary retention is a common complication after mixed hemorrhoid surgery, referring to the inability of urine in the bladder to be normally expelled, leading to urine retention. This condition not only prolongs the postoperative recovery time and increases medical costs, but may also cause problems such as urinary tract infections and bladder dysfunction. The pathogenesis of urinary retention after mixed hemorrhoid surgery is complex, involving multiple factors such as the type of surgery, anesthesia method, individual differences among patients, postoperative pain management and psychological stress. Although there are various clinical treatment methods, their efficacy varies among individuals. This article reviews relevant literature from 2018 to 2024, analyzing the etiology of urinary retention after mixed hemorrhoid surgery. It summarizes the intervention measures and mechanisms of non-pharmacological treatments, such as physical therapy and analgesic techniques, as well as pharmacological treatments, including anticholinesterase drugs, selective α-receptor blockers and analgesics drugs, so as to provide the reference for the prevention and treatment of urinary retention after mixed hemorrhoid surgery.