ObjectiveNeuroinflammation plays a crucial role in both the onset and progression of ischemic stroke, exerting a significant impact on the recovery of the central nervous system. Excessive neuroinflammation can lead to secondary neuronal damage, further exacerbating brain injury and impairing functional recovery. As a result, effectively modulating and reducing neuroinflammation in the brain has become a key therapeutic strategy for improving outcomes in ischemic stroke patients. Among various approaches, targeting immune regulation to control inflammation has gained increasing attention. This study aims to investigate the role of in vitro induced regulatory T cells (Treg cells) in suppressing neuroinflammation after ischemic stroke, as well as their potential therapeutic effects. By exploring the mechanisms through which Tregs exert their immunomodulatory functions, this research is expected to provide new insights into stroke treatment strategies. MethodsNaive CD4⁺ T cells were isolated from mouse spleens using a negative selection method to ensure high purity, and then they were induced in vitro to differentiate into Treg cells by adding specific cytokines. The anti-inflammatory effects and therapeutic potential of Treg cells transplantation in a mouse model of ischemic stroke was evaluated. In the middle cerebral artery occlusion (MCAO) model, after Treg cells transplantation, their ability to successfully migrate to the infarcted brain region and their impact on neuroinflammation levels were examined. To further investigate the role of Treg cells in stroke recovery, the changes in cytokine expression and their effects on immune cell interactions was analyzed. Additionally, infarct size and behavioral scores were measured to assess the neuroprotective effects of Treg cells. By integrating multiple indicators, the comprehensive evaluation of potential benefits of Treg cells in the treatment of ischemic stroke was performed. ResultsTreg cells significantly regulated the expression levels of both pro-inflammatory and anti-inflammatory cytokines in vitro and in vivo, effectively balancing the immune response and suppressing excessive inflammation. Additionally, Treg cells inhibited the activation and activity of inflammatory cells, thereby reducing neuroinflammation. In the MCAO mouse model, Treg cells were observed to accumulate in the infarcted brain region, where they significantly reduced the infarct size, demonstrating their neuroprotective effects. Furthermore, Treg cell therapy notably improved behavioral scores, suggesting its role in promoting functional recovery, and increased the survival rate of ischemic stroke mice, highlighting its potential as a promising therapeutic strategy for stroke treatment. ConclusionIn vitro induced Treg cells can effectively suppress neuroinflammation caused by ischemic stroke, demonstrating promising clinical application potential. By regulating the balance between pro-inflammatory and anti-inflammatory cytokines, Treg cells can inhibit immune responses in the nervous system, thereby reducing neuronal damage. Additionally, they can modulate the immune microenvironment, suppress the activation of inflammatory cells, and promote tissue repair. The therapeutic effects of Treg cells also include enhancing post-stroke recovery, improving behavioral outcomes, and increasing the survival rate of ischemic stroke mice. With their ability to suppress neuroinflammation, Treg cell therapy provides a novel and effective strategy for the treatment of ischemic stroke, offering broad application prospects in clinical immunotherapy and regenerative medicine.

AIM: To investigate the effects of hypobaric hypoxia in plateau on tear indexes and related anatomical structures in rabbits.METHODS: A total of 18 healthy New Zealand rabbits were selected and randomly divided into plateau group and control group, with 9 rabbits(18 eyes)in each group. The plateau group was housed in the Simulated Climate Cabin for Special Environment of Northwest of China, simulating hypobaric hypoxia at an altitude of 6 000 m. The control group was housed in a clean animal room with atmospheric pressure and oxygen. Changes in the tear meniscus height and non-invasive tear break-up time were detected by using RHCT-1 corneal topographer dry eye comprehensive analysis system, changes in tear secretion was measured by Schirmer Ⅰ test, before intervention and on the 3, 7 d, 2 and 4 wk. Meanwhile, the changes in tear composition before and after intervention in the plateau environment were analyzed using Raman Spectroscopy. The histopathological changes of the lower lid conjunctiva, cornea, lacrimal gland, and Hardarian gland were observed by hematoxylin-eosin(HE)staining after 4 wk of intervention, and the expression of mucin 5AC(MUC5AC)in conjunctiva was detected by immunohistochemistry.RESULTS: Compared with the control group, Schirmer Ⅰ test, tear meniscus height, first and average non-invasive tear break-up time in the plateau group decreased significantly since 3 d, and the difference was significant with the extension of observation time(P<0.05). The above indexes increased from 2 wk. After 4 wk of intervention, the protein and lipid content of the tear composition of rabbits in the plateau group increased, and the nucleic acid content decreased compared with the pre-intervention period. Compared with the control group, rabbits in the plateau group showed thickening of corneal stromal edema, an increase in the number of conjunctival cup cells, increase in the level of expression of MUC5AC, an increase in the level of expression of MUC5AC, an atrophy and flattening of cytoplasm in lacrimal epithelial cells, an enlargement of glandular lumen, and no obvious destructive changes in the Hardarian glands.CONCLUSION: Acute plateau environment can destroy the homeostasis of rabbit ocular surface, so that the tear secretion and the tear film stability decreases, but within a certain period of time, rabbits undergo compensation with the habituation to the hypobaric hypoxia environment, which can increase the tear secretion to a certain extent and restore the tear film stability.

AIM: To analyze and screen influencing factors of diabetic patients complicated with retinopathy, and establish and validate prediction model of nomogram.METHODS: A total of 1 252 patients from the Diabetes Complications Early Warning Dataset of the National Population Health Data Archive(PHDA)between January 2013 to January 2021 were selected and randomly divided into a modeling group(n=941)and a validation group(n=311). Univariate analysis, LASSO regression and Logistic regression analysis were used to screen out the influencing factors of diabetic retinopathy, and a nomogram prediction model was established. The receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve were used to evaluate the model. The clinical benefit was evaluated by the decision curve analysis(DCA).RESULTS: Age, hypertension, nephropathy, systolic blood pressure(SBP), glycated hemoglobin(HbA1c), high-density lipoprotein cholesterol(HDL-C), and blood urea(BU)were the influencing factors of diabetic retinopathy. The area under the curve(AUC)of the modeling group was 0.792(95%CI: 0.763-0.821), and the AUC of the validation group was 0.769(95%CI: 0.716-0.822). The Hosmer-Lemeshow goodness of fit test and calibration curve suggested that the theoretical value of the model was in good agreement(modeling group: χ2=14.520, P=0.069; validation group: χ2=14.400, P=0.072). The DCA results showed that the threshold probabilities range was 0.09-0.89 for modeling group and 0.07-0.84 for the validation group, which suggested the clinical net benefit was higher.CONCLUSION: This study constructed a risk prediction model including age, hypertension, nephropathy, SBP, HbA1c, HDL-C, and BU. The model has a high discrimination and consistency, and can be used to predict the risk of diabetic retinopathy in patients with diabetes.

To characterize human antibodies against low-calcium response V(LcrV)antigen of Yersinia pestis,the mono-clonal antibodies were screened and assayed.Antibody gene was derived from peripheral blood mononuclear cells of the vaccin-ees immunized by plague subunit vaccine in phase Ⅱb clinical trial.Human ScFv antibody library was constructed by phage dis-play.After panning library by using recombinant LcrV antigen,antibody variable genes were sequenced and converted into IgG1 format to evaluate its binding specificity and relevant parameters.An anti-plague human ScFv antibody library was estab-lished contained 7.54× 108 independent clones.After panning by LcrV antigen,3 human antibodies named as RV-B4,RV-D1 and RV-E8,respectively,were identified.Using indirect enzyme-linked immunosorbent assay(ELISA)and Western blot(WB),the specific bindings of the mAbs to LcrV antigen were confirmed.The dissociation constant(KD)of them to LcrV is 2.1 nmol/L,1.24 nmol/L and 42 nmol/L,respectively.Minor protective efficacy was found among 3 human antibodies in Y.pestis 141-infected mice.Three anti-LcrV monoclonal antibodies generated from immunized vaccinees were binding specific antibod-ies and could not block plague infection in mice.These antibodies are the potential candidate reagents for basic research of plague immunity and the application of plague diagnosis.

Objective:To evaluate the outcomes of reconstruction with half of peroneous longus tendon autograft for the treatment of chronic Achilles tendon rupture combined with tendon defects.Methods:A retrospective case series study was conducted on the clinical data of 14 patients with chronic tendon rupture combined with defects admitted to Orthopedic Sports Medicine Center, West China Hospital, Sichuan University from November 2017 to August 2020, including 11 males and 3 females, aged 26-62 years [(42.8±10.7)years]. All the patients underwent Achilles tendon reconstruction with half of peroneus longus tendon autograft. American Orthopedic Foot and Ankle Society (AOFAS) score, Achilles tendon total rupture score (ATRS) and Visual Analogue Scale (VAS) were compared before surgery, at 12 months after surgery and at the last follow-up. At the last follow-up, MRI of the injured ankle was prescribed to evaluate tendon healing; Thomspon test was performed and the patients were asked to do single-leg heel raise; the patients were asked about their conditions in returning to daily life activities and sports. Postoperative complications were observed.Results:All the patients were followed up for 24-47 months [(35±9)months]. AOFAS score, ATRS and VAS at 12 months after surgery were (87.9±6.6)points, (80.9±2.4)points and (2.0±0.3)points respectively, superior to those before surgery [(52.7±16.9)points, (42.0±4.4)points and (4.1±0.4)points respectively] ( P<0.05). The afore-mentioned results at the last follow-up were (95.2±7.2)points, (85.9±2.5)points and (0.8±0.3)points respectively, superior to those at 12 months after surgery ( P<0.05). MRI images of the affected ankle joints showed satisfactory healing of the reconstructed Achilles tendon at the last follow-up. All the patients, being negative in Thompson test at the last follow-up, were able to complete the heel lift on the affected side. All the patients resumed activities of daily living at the last follow-up, among whom 5 resumed to moderate- to high-intensity sports activities, such as basketball sport, and moderate-to high-intensity physical training, 5 resumed light-intensity sports activities such as jogging and swimming, and the other 4 did not resume sports due to fear of re-injury or aging. One patient had delayed wound healing, which was considered gout-related. One patient complained about mild pain at the Achilles tendon in cold weather or after long walks. No re-rupture of the Achilles tendon occurred. No patient complained about discomfort at the graft harvest site, calcaneal valgus or restricted ankle plantar flexion. Conclusions:For patients with chronic Achilles tendon rupture combined with tendon defects, reconstruction with half of peroneous longus tendon autograft facilitates postoperative spinal function recovery and pain alleviation, achieves satisfaction with the returning to daily activity and sports, and has few complications.

Objective To analyze the risk factors influencing the occurrence of atherosclerosis in patients with type 2 diabetes, and to construct and evaluate a nomogram prediction model. Methods Multivariate logistic regression was used to analyze the risk factors of atherosclerosis in type 2 diabetes mellitus, and R software was used to build a nomogram prediction model. The accuracy and clinical validity of the model were verified by using H-L fit curve, area under ROC curve and calibration curve. Results The prevalence rate of atherosclerosis was 56.37%. Independent risk factors for atherosclerosis in type 2 diabetes mellitus (P<0.05) were body weight (OR=1.42，P<0.05), glycated serum protein (OR=1.35, P<0.05), lactate dehydrogenase (OR=1.17, P<0.05), alkaline phosphatase (OR=0.79, P<0.05), hyperlipidemia (OR=2.30, P<0.05), stroke (OR=4.20, P<0.05), coronary heart disease (OR=64.54, P<0.05), lower extremity artery disease (OR=24.52, P<0.05), and other endocrine diseases (OR=1.65 , P<0.05). The area under ROC curve was 0.91, the slope of the calibration curve was close to 1, and the H-L fit curve χ²=3.11. The internal verification result of the constructed nomogram prediction model was P=0.93. External verification of patients in the test set showed that the area under ROC curve was 0.91, indicating good differentiation and accuracy of the model. Conclusion The prediction model established by using the risk factors screened in this study has a high accuracy and differentiation, and medical staff can take effective prevention measures according to the individual factors of patients.

Dementia in traditional Chinese medicine （TCM） mainly presents amnesia and dullness. Alzheimer's disease and vascular dementia belong to the category of dementia in TCM. These progressive neurological diseases have a complex etiology and a long course， and the drugs that can reverse the disease course remain to be developed. Therefore， early intervention plays a vital role in delaying the disease progression. Apathy refers to a lack of motivation that leads to the attenuation or disappearance of goal-directed behaviors， cognitive functions， and emotional responses. Clinical studies have suggested that apathy exists in the early stage of a variety of neurodegenerative diseases， being one of the key symptoms to the early diagnosis of dementia. The severity of apathy is related to the severity of dementia. Therefore， early diagnosis and treatment of apathy are of great significance to the prevention and treatment of dementia. The preclinical research on apathy in dementia is still in its infancy， and the systematic evaluation method has not been prescribed. The clinical diagnosis and treatment are also in the exploratory stage， and the complex pathophysiological mechanisms of apathy and dementia development have not been fully elucidated. This article reviews the research progress of apathy in dementia， the apathetic behaviors of dementia animal models， the behaviors of patients with apathy， and the treatment methods in recent years and summarizes the research status of apathy in dementia. This review aims to provide a theoretical basis for exploring the behavior of apathy in dementia and conducting preclinical research and evaluation of the pathogenesis and to lay a foundation for the treatment of apathy in dementia.

Traditional Chinese medicine （TCM） has a long history of application in China and has consistently played a vital role in treating diseases and saving lives. TCM prescriptions （compounds） constitute the primary form of clinical TCM treatment and significantly differ from western medicine （chemicals） due to the diverse composition and chemical constituents of TCM （compounds）. Nevertheless， the potential multi-component， multi-target， and multi-pathway action characteristics of TCM prescriptions also demonstrate their possible （complementary） therapeutic advantages when compared with single-component chemical drugs. Therefore， driven by the development of modern science and technology and the demands of the modernization and internationalization of TCM， modern theories regarding the complexity of TCM prescription effects have been continuously proposed： Different from the abstract language of traditional prescription theory， the modern TCM prescription theory is more inclined to illustrate the connotation of prescription compatibility concretely and vividly from an experimental and scientific perspective. In this paper， new theories on the complexity of TCM prescriptions proposed in recent years are summarized to provide research references and ideas for the greater role of TCM prescriptions and a better scientific understanding.

The voltage-gated sodium channel subtype Nav1.7 is highly expressed in nociceptive sensory neurons and is a key pathogenic target in several human hereditary pain syndromes. In recent years, a large number of studies have shown that Nav1.7 plays an important role in inflammatory, neuropathic, and nociceptive pain. Therefore, targeting Nav1.7 is a new strategy and hotspot for the development of novel analgesics. This review introduces the structure and function of Nav1.7, its regulatory role in pain, highlights the development progress of small-molecule Nav1.7 inhibitors in clinical trials, and analyzes the preclinical development of highly specific Nav1.7 inhibitors, with a view to providing reference for the development of Nav1.7 analgesic drugs.

In the context of comprehensively strengthening party building in public hospitals,multiple medical institu-tions have extended party building to the construction of medical union,explored the establishment of medical union party building alliances,and accumulated rich experience in the integration and development of party building and business.This article takes the Medical Union of the First People's Hospital of Suqian City as an example to deeply summarize and analyze the experience,practices,and existing problems in the process of medical union construction,propose countermeasures and suggestions,and pro-vide beneficial practice and exploration for other medical union party building.