Mitochondrial dysfunction in chondrocytes is a key pathogenic factor in osteoarthritis (OA), but directly modulating mitochondria in vivo remains a significant challenge. This study is the first to verify a correlation between mitochondrial dysfunction and the downregulation of the FOXO3 gene in the cartilage of OA patients, highlighting the potential for regulating mitophagy via FOXO3 gene modulation to alleviate OA. Consequently, we developed a chondrocyte-targeting CRISPR/Cas9-based FOXO3 gene-editing tool (FoxO3) and integrated it within a nanoengineered 'truck' (NETT, FoxO3-NETT). This was further encapsulated in injectable hydrogel microspheres (FoxO3-NETT@SMs) to harness the antioxidant properties of sodium alginate and the enhanced lubrication of hybrid exosomes. Collectively, these FoxO3-NETT@SMs successfully activate mitophagy and rebalance mitochondrial function in OA chondrocytes through the Foxo3 gene-modulated PINK1/Parkin pathway. As a result, FoxO3-NETT@SMs stimulate chondrocytes proliferation, migration, and ECM production in vitro, and effectively alleviate OA progression in vivo, demonstrating significant potential for clinical applications.

To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.

Chronic obstructive pulmonary disease (COPD), a respiratory disease characterized by inflammation due to neutrophil infiltration, has become the third leading cause of death worldwide. After the occurrence of COPD, the persistent accumulation of neutrophils can promote the excessive formation of neutrophil extracellular traps (NETs), which plays an important role in local capture and clearance of pathogens, rapid control of infection, and immune regulation. This article mainly introduces the mechanism of COPD occurrence and NETs formation as well as the research progress of NETs in COPD, and summarizes the relevant drug targets for COPD treatment based on NETs, aiming to provide a reference for further research.

Ischemic stroke, a cerebrovascular disease with high incidence, high mortality, high disability rate and high recurrence rate, is an important cause of death and disability of middle-aged and elderly people in China, and imposes a huge burden to society and families. Therefore, it is essential to identify the risk factors associated with ischemic stroke and effectively prevent them. Studies have shown that obstructive sleep apnea is an independent risk factor for ischemic stroke. However, the exact pathological mechanism of their association has not been clarified. With the development of next-generation sequencing technology, more and more studies have focused on intestinal microbiota. They have found that obstructive sleep apnea can cause intestinal microbiota changes, and intestinal microbiota may be closely related to ischemic stroke. Therefore, this paper attempts to investigate the relationship between intestinal flora and ischemic stroke, so as to reveal the potential pathological mechanism of ischemic stroke caused by obstructive sleep apnea.

Obstructive sleep apnea (OSA) is a common sleep disordered breathing disorder. As a major global public health problem, untreated OSA can lead to a variety of adverse health outcomes, including various cardiovascular and cerebrovascular diseases, metabolic disorders, and psychiatric disorders such as anxiety and depression. Traditional OSA therapies such as positive airway pressure (PAP), weight loss, oral appliance, upper airway surgery, and postural therapy focus on the anatomical factors of OSA. However, the pathogenesis of OSA is heterogeneous, and non-anatomical factors also play an important role in most patients. Although there is no drug with exact efficacy for the treatment of OSA, with the deepening understanding of the pathophysiological mechanism of OSA, more and more clinical studies are devoted to the study of drug treatment of OSA and its complications, and a series of results have been achieved. The following is a review of the relevant studies on drug treatment of OSA in recent years, hoping to provide literature support and theoretical basis for future research on drug treatment of OSA.

Mesenchymal stem cells(MSCs)are self-regenerating,rapidly proliferating pluripotent stem cells that depend primarily on their derived pro-angiogenic,inflammatory regulatory,and tro-phic factors to exert beneficial effects that attenu-ate deleterious inflammatory responses,reduce vascular damage,and promote tissue repair and re-generation.Obstructive sleep apnea hypoventila-tion syndrome(OSAHS)is a chronic disorder marked by oropharyngeal collapse during sleep,re-sulting in transient reduced airflow,large fluctua-tions in intrathoracic pressure,and intermittent hy-poxia and hypercapnia.OSAHS subsequently cyto-kine-mediated inflammatory cascades,oxidative stress,and ischemia,recruit MSCs from inflamed and damaged tissues through MSCs-derived of anti-inflammatory and pro-angiogenic factor activity,re-duce hypoxia,suppress inflammation,promote re-generation,and prevent fibrosis in OSAHS-injured tissues.In this paper,we will describe the patho-genesis of inflammation,oxidative stress,fibrosis and ischemia from the perspective of OSAHS,high-lighting the current research progress on MSCs-de-pendent regulation of OSAHS-related pathology.

ObjectiveTo classify subtypes among middle-aged and elderly type 2 diabetes mellitus (T2DM) patients aged between 35‒74 years in Shanghai suburbs, to compare their characteristics and analyze incidence risk for cerebrovascular disease among these subtypes, so as to promote personalized and precise treatment of T2DM. MethodsA total of 7 792 patients with T2DM who completed a baseline survey from 2016 and 2019 were selected as the research subjects, based on the data from a natural population cohort and biobank in Shanghai suburbs. Patients were stratified by gender and clustered into subtypes using k-means method based on baseline parameters including the age at T2DM diagnosis, body mass index (BMI), fasting blood glucose, and triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C). Patients were followed up until March 31, 2023. Multivariate Cox regression models were used to analyze the association between subtypes and incidence risk for cerebrovascular disease, and those with cerebrovascular disease within 1 year of follow-up survey were excluded from sensitivity analysis. ResultsAmong the 7 792 patients with T2DM, 3 615 were males and 4 177 were females. Stratified by gender, 4 subgroups were identified through k-means clustering analysis, namely poor blood glucose control subgroup, severe insulin-resistant subgroup, younger onset subgroup, and older onset subgroup. The median follow-up time was 4.30 years, during which 1 960 cerebrovascular disease events were observed (844 in males, 1 116 in females). After adjusting for smoking, alcohol consumption, weekly exercise, family history of diabetes mellitus, and duration of diabetes mellitus, among male patients, the incidence risk for cerebrovascular disease was lower in the younger onset subgroup (HR=0.59, 95%CI: 0.48‒0.73, P<0.001), poor blood glucose control subgroup (HR=0.81, 95%CI: 0.65‒1.00, P=0.046), and severe insulin-resistant subgroup (HR=0.61, 95%CI: 0.50‒0.75, P<0.001), compared to the older onset subgroup. While among female patients, the incidence risk for cerebrovascular disease was also lower in the younger onset subgroup (HR=0.68, 95%CI: 0.57‒0.80, P<0.001), poor blood glucose control subgroup (HR=0.73, 95%CI: 0.60‒0.89, P=0.002), and severe insulin-resistant subgroup (HR=0.72, 95%CI: 0.61‒0.85, P<0.001), compared to the older onset subgroup. Results of the sensitivity analysis were consistent with the main findings. ConclusionAmong middle-aged and elderly T2DM patients in suburban Shanghai, both male and female patients have the highest incidence risk for cerebrovascular disease in the older onset subgroup. Subtyping of T2DM patients can help to identify the high-risk populations of cerebrovascular disease.

Objective:To simulate the neuroendoscopy assisted contralateral cervical 7 (C 7) nerve transfer via prespinal route and measure its relevant anatomical landmarks to explore the clinical feasibility and efficacy of this surgical approach for central upper limb spastic paralysis. Methods:(1) Six fresh cadaver specimens of the head and neck were obtained. Linear incisions of approximately 5 cm were made above the midpoint of the bilateral clavicles to simulate neuroendoscopy assisted contralateral C 7 nerve transfer via prespinal route. With the superior margin of midpoint of the clavicle as central point, distance to the distal bifurcation of the C 7 nerve, distances to the superior or inferior trunks of the proximal brachial plexus nerves, and distances to the exit of the intervertebral foramina of the C 6, C 7, and C 8 nerves were measured. (2) One patient with upper limb spastic paralysis after intracerebral hemorrhage accepted neuroendoscopy assisted contralateral C 7 nerve transfer via prespinal route; the clinical data and efficacy of the patient were retrospectively analyzed. Results:(1) The C 7 nerve, the upper trunk of brachial plexus formed by the C 5 and C 6 nerves and the lower trunk of brachial plexus formed by the C 8 and T 1 nerves could be exposed after neuroendoscopy assisted contralateral C 7 nerve transfer via prespinal route. The distance between the superior margin of midpoint of the clavicle and the distal bifurcation of the C 7 nerve is (2.20±0.11) cm, and its distance to the superior trunk of the proximal brachial plexus is (2.62±0.10) cm, and its distance to the inforior trunk of the proximal brachial plexus nerve is (2.72±0.11) cm. The distance between the superior margin of midpoint of the clavicle and the proximal C 7 nerve (at the exit of the intervertebral foramen) is (7.22±0.15) cm, its distance to the proximal C 6 nerve (at the exit of the intervertebral foramen) is (7.84±0.12) cm, and its distance to the proximal C 8 nerve (at the exit of the intervertebral foramen) is (6.96±0.12) cm. (2) The patient with central upper limb spastic paralysis accepted neuroendoscopy assisted contralateral C 7 nerve transfer via prespinal route successfully, with surgical time lasting for 2 h and bleeding amount of 20 mL. After surgery, the incision healed well, and the patient experienced pain and numbness in the healthy side of the upper limb with subsided symptoms one month after surgery. The spasticity symptoms of the affected upper limb obviously improved after surgery with decreased muscle tone. Follow-up after discharge was performed for 14 months, and the muscle strength of the affected upper limb recovered to level 1 +. Conclusion:Neuroendoscopy assisted contralateral C 7 nerve transfer via prespinal route can expose the proximal and distal C 7 nerves, with minimal invasion; this clinical study has preliminarily confirmed the safety and effectiveness of this transfer via prespinal route in central upper limb spastic paralysis.

Objective To investigate the occurrence of intraoperative frozen section(FS)pathology unclear diagnosis in thyroid carcinoma,seeking clinical factors affecting the pathological accuracy of FS.Methods Retrospective analysis of thyroid cancer patients who underwent surgical treatment at People's Hospital of Daxing District in Beijing from August 2016 to December 2019.Target nodules were divided into FS clear diagnosis group and unclear diagnosis group(including delayed diagnosis group,misdiagnosis group,accidental diagnosis group)according to the results of FS and paraffin section pathological examination.The general information,laboratory test,result of color ultrasound and pathological types between FS clear diagnosis group and unclear diagnosis group were compared.Results A total of 336 cancer nodules were included.The quantity and proportion of cancer nodules in clear diagnosis group,delayed diagnosis group,misdiagnosis group and accidental diagnosis group were respectively 266(79.17%),28(8.33%),21(6.25%)and 21(6.25%).In the delayed diagnosis group,"no exception"thyroid cancer was the most frequently used.Compared to clear diagnosis group,the maximum diameter of cancer nodules in delayed diagnosis group,misdiagnosis group,accidental diagnosis group were smaller(P<0.05);In the delayed diagnosis group,the proportion of aspect ratio>1 was higher(P=0.017),and the proportion of microcalification was lower(P=0.002).In the misdiagnosis group,thyroid peroxidase antibody level was higher(P=0.002).Conclusion Clinical doctors should be familiar with commonly used diagnostic terms for delayed diagnosis and misdiagnosis.When making treatment decisions,full consideration should be given to the possibility of difficult to diagnose diagnosis,especially for patients with small nodules and concurrent chronic lymphocytic thyroiditis.

Obstructive sleep apnea(OSA)can lead to complications in various systems and or-gans of the body.Dry eye(DE),the most common ocular surface disease in clinical practice,affects visual-related daily activities and work in varying degrees.Recent studies have revealed a potential re-lationship between OSA and DE.OSA can induce DE through a series of mechanisms such as oxidative stress,inflammation,rhythm disorder and so on,and the combination of OSA and DE may profoundly affect the sleep health,mood disorders,and quality of life of patients in a new form overall.However,there is still a lack of systematic understanding of the comorbidity of OSA and DE,resulting in insuffi-cient screening,diagnosis and treatment of OSA related DE in clinical practice.This paper provided a review of the relationship between OSA and DE to raise awareness among clinicians of the diagnosis and management of DE during OSA treatment.