Aging is typically associated with decreased musculoskeletal function, leading to reduced mobility and increased frailty. As a hallmark of aging, cellular senescence plays a crucial role in various age-related musculoskeletal diseases, including osteoporosis, osteoarthritis, intervertebral disc degeneration, and sarcopenia. The detrimental effects of senescence are primarily due to impaired regenerative capacity of stem cells and the pro-inflammatory environment created by accumulated senescent cells. The secreted senescence-associated secretory phenotype (SASP) can induce senescence in neighboring cells, further amplifying senescent signals. Although the removal of senescent cells and the suppression of SASP factors have shown promise in alleviating disease progression and restoring musculoskeletal health in mouse models, clinical trials have yet to demonstrate significant efficacy. This review summarizes the mechanisms of cellular senescence in age-related musculoskeletal diseases and discusses potential therapeutic strategies targeting cellular senescence.
Humans ; Cellular Senescence/physiology* ; Musculoskeletal Diseases/pathology* ; Aging/pathology* ; Animals ; Senescence-Associated Secretory Phenotype/physiology* ; Sarcopenia ; Osteoporosis

Objective:To investigate the development of receptive and expressive vocabulary in Mandarin-speaking children with cochlear implants (CI) during the first year after CI activation.Methods:A total of 827 children (411 boys and 416 girls) who were implanted CI before 2.5 years of age from October 2019 to December 2022 in the Department of Auditory Implantation, Shandong Provincial ENT Hospital were included in this study. The Infant Checklist of the Mandarin Early Vocabulary Inventory (EVI) was used to assess the quantity and content of receptive and expressive vocabulary at the time of CI activation and at the 1st, 3rd, 6th, 9th, 12th months post-activation. SPSS 22.0 was used to describe the receptive and expressive vocabulary of CI children at the first year after activation.Results:During the first year after CI activation, CI children′s receptive and expressive vocabulary consistently increased with the CI usage. The average number of receptive vocabulary and expressive vocabulary respectively increased from 0 to 178, and from 0 to 97. At the first year of post-activation, the number of receptive and expressive vocabulary of CI children were superior to that of hearing-age matched typical-hearing children, but fell behind of that of chronological age matched typical-hearing children. In terms of lexical categories, receptive and expressive vocabulary was acquired in the following order: nouns, verbs, adjectives, and pronouns. Among the top 50 words that CI children could express, nouns were the most common, then followed by verbs, adjectives, and pronouns. Father′s education level can significantly and positively predictethe receptive vocabulary of CI children at the first year post-activation. At the first year after CI activation, the 10th, 25th, 50th, 75th, and 90th percentiles were 113, 149, 178, 202, 223 for the receptive vocabulary, and 9, 37, 97, 148, 188 for expressive vocabulary.Conclusion:For Mandarin speaking children with CI, the receptive and expression vocabulary continuely increased within the first year after CI activation. The ability to grasp receptive vocabulary precedes the ability to express expressive vocabulary. Compared to hearing-age matched typical-hearing children, CI children showed faster rate of the vocabulary growth, and earlier and more frequently verb expression. However, it still larged behind that of chronological age matched hearing normal children. CI children respectively understood and expressed nouns and verbs the first. In children with CI, the first concepts understood and expressed were nouns and verbs. Among the first 50 words expressed, nouns were the most numerous, and the age at which verbs were acquired was earlier than that for hearing-age matched typical-hearing children.

Objective:To analyze the clinical characteristics, diagnosis and treatments of patients with POEMS syndrome initially diagnosed as pulmonary hypertension (PH).Methods:Clinical data of 7 patients who were initially diagnosed as PH and finally diagnosed as POEMS syndrome in Shanghai Pulmonary Hospital from May 2013 to November 2021 were retrospectively reviewed. Clinical manifestations, laboratory tests, echocardiography, hemodynamic findings, treatment and prognosis of patients were analyzed.Results:Seven patients, including 4 males and 3 female, aged (55±9) (44-62) years were presented with elevated pulmonary artery pressure by echocardiography at admission. Chest tightness and shortness of breath (7/7), fatigue (6/7) and lower limb edema (4/7) were the most common symptoms in the first-episode. Meanwhile, patients also presented symptoms associated with POEMS syndrome, including multiple peripheral neuropathy (7/7), multiserosal cavity effusion (6/7), organomegaly (5/7), skin changes (5/7), and endocrine lesions (4/7). Serum levels of vascular endothelial growth factor (VEGF) were significantly increased in all patients. The pulmonary arterial systolic blood pressure was (66±21)mmHg (1 mmHg=0.133 kPa) estimated by echocardiography. Six patients underwent right heart catheterization and significantly increased mean pulmonary artery pressure((35±9) mmHg) was confirmed; and their pulmonary vascular resistance was (4.00±2.10) Wood U. All patients received corresponding treatment for POEMS syndrome. The excise tolerance was improved in 5 patients after successful treatment with stable or reversed WHO functional class. One patient received hemodialysis treatment for uncontrolled POEMS. One patient died during follow-up. The echocardiography was followed up in 4 patients, and 2 of whom had a complete reversal of PH, 1 had a partial reversal, and 1 had not yet reversed.Conclusions:In patients with PH who have multisystem manifestations, such as multiple peripheral neuropathy, multiserosal cavity effusion, organomegaly and skin changes, POEMS syndrome should be considered, and proper and active treatment of POEMS may reverse PH and improve the prognosis of patients.

BackgroundIn relation to neurodevelopmental hypothesis in the etiology of schizophrenia， brain-derived neurotrophic factor （BDNF） as a neurotrophin occupies a relatively dominant position in neuronal development and is a potential biomarker for schizophrenia， and previous studies have suggested that its serum concentration and genetic polymorphisms play a vital role in the pathogenesis of schizophrenia， but this remains controversial. ObjectiveTo analyze the difference in BDNF serum concentration between schizophrenic patients and healthy controls， and to explore the correlation of three BDNF single nucleotide polymorphism （SNPs） including rs11030101， rs2030324 and rs6265 with BDNF serum concentration and clinical symptoms in patients with schizophrenia， thus providing references for the clinical treatment of schizophrenia. MethodsA case-control study was conducted on 55 patients with schizophrenia who attended the Zhongshan Third People's Hospital from January 2019 to December 2020 and met the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5）， and 31 healthy controls concurrently recruited from the hospital or general population. Positive and Negative Symptom Scale （PANSS） was utilized to evaluate the psychiatric symptoms of patients with schizophrenia. BDNF serum concentration in all participants was measured using enzyme-linked immunosorbent assay （ELISA）， and the genotype distributions of three BDNF SNPs （rs11030101， rs2030324， rs6265） were investigated by polymerase chain reaction sequence-based typing method. ResultsBDNF serum concentration in patient group was lower than that in control group， with statistical difference （t=-3.804， P<0.01）. In terms of clinical symptoms， PANSS total score， excitement/hostility domain score， and depression/anxiety domain score demonstrated statistical difference among patients with different genotypes at SNP rs11030101 （t=2.022， Z=-2.696， -2.467， P<0.05 or 0.01）. No statistical difference was noted in BDNF serum concentration in patients with different genotypes at three BDNF SNPs （Z=1.483， F=2.584， 0.417， P>0.05）. ConclusionPatients with schizophrenia are found to have low BDNF serum concentration， and the three BDNF SNPs （rs11030101， rs2030324， rs6265） are not associated with BDNF serum concentration， whereas the BDNF rs11030101 polymorphism may contribute to the manifestation of clinical symptoms of excitement/hostility and depression/anxiety in patients with schizophrenia. Furthermore， BDNF serum concentration seems to be more dependent on clinical diagnosis effect rather than genetic polymorphism. ［Funded by Guangdong Province Medical Science and Technology Research Fund Project （number， A2021205）； Zhongshan Medical Research Program （number， 2022J221）］

Natural extracellular vesicles (EVs) play important roles in many life processes such as in the intermolecular transfer of substances and genetic information exchanges. Investigating the origins and working mechanisms of natural EVs may provide an understanding of life activities, especially regarding the occurrence and development of diseases. Additionally, due to their vesicular structure, EVs (in small molecules, nucleic acids, proteins, etc.) could act as efficient drug-delivery carriers. Herein, we describe the sources and biological functions of various EVs, summarize the roles of EVs in disease diagnosis and treatment, and review the application of EVs as drug-delivery carriers. We also assess the challenges and perspectives of EVs in biomedical applications.

Objective BAG3-related myopathy is a rare condition so far reported in twenty patients worldwide.The purpose of this study was to draw attention to this rare disease and to the fact that BAG3-related myopathy should be considered as a rare differential diagnosis of hypercapnia.Methods We report a sporadic case of a 14-year-old Chinese girl with a de novo p.Pro209Leu mutation in BAG3 and reviewed the literatures for reported cases related to this mutation.Results We described a 14-year-old Chinese girl who presented with gradually appearing symptoms of hypercapnia that required assisted ventilation.The muscle biopsy and the blood whole-exome sequencing results confirmed the diagnosis of myofibrillar myopathy with a de novo p.Pro209Leu mutation in BAG3.Totally twenty-one patients from twenty families with a confirmed diagnosis of BAG3-related myopathy were reported to date,including this patient and literature review.The male to female ratio was 11 :10 and most showed initial symptoms in the first decade of life.Most patients presented toe/clumsy walking or running as the onset symptom,followed by muscle weakness or atrophy.Creatine kinase levels were elevated in fourteen patients and were normal in three.Eighteen patients developed respiratory insufficiency during the disease course and thirteen (one could not tolerate non-invasive assisted ventilation) required non-invasive assisted ventilation for treatment.Except for one not reported,heart involvement was found in seventeen patients during the disease course and seven underwent heart transplantation.Z-disk streaming and aggregation could be observed in most of the patients' muscle histology.In the long-term follow-up,five patients died of cardiac or respiratory failure.Conclusion BAG3-associated myopathy is a rare type of myofibrillar myopathy.It should be considered as a rare differential diagnosis of hypercapnia.

The clinical application of triptolide (TPL) in tumor therapy has been greatly limited by its toxicity and inefficient delivery. Herein, a localized and sustained-release thermo-sensitive hydrogel was developed for the intra-tumor administration of TPL. Based on the amphiphilic structure of poly (

Objective To investigate the effects of high energy enteral nutrition (EN) on nutritional status and immune function in patients with heart failure caused by pulmonary cardiac disease. Methods Eighty-six patients with heart failure caused by pulmonary heart disease were continuously collected from March 2017 to March 2018 in the Department of Critical Care Medicine of Taizhou First People's Hospital, and they were divided into a high-energy EN group and a standard EN group according to the different use of EN preparations, each group with 43 cases. The high-energy EN group were treated with high energy EN solution TPF-T (Ruineng), and the standard EN group were treated with standard EN solution TP (Ruisu); the initial EN infusion velocity in all the patients was 25 mL/h, the calorific calorie would reach the target to 104.6-125.5 kJ·kg-1·d-1, and the protein would target to 1.5-2 g·kg-1·d-1 within 3 days;the blood glucose was controlled within the scope of 7.8-11.1 mmol/L. The differences in rates of calorie and protein goal targeting situations, nutritional status, inflammatory response and immune function were compared between the two groups. Results From the 3rd day to 7th day after EN application, the rates of calorie and protein goal targeted in the high-energy EN group were significantly higher than those in the standard EN group [calorie targeted rate: 69.77% (30/43) vs. 41.86% (18/43), protein targeted rate: 25.58% (11/43) vs. 11.63% (5/43), all P < 0.05]. With the extension of EN application, nutritional indexes such as albumin (Alb), prealbumin (PA), transferrin (TRF), etc. and the immune indexes such as human leucocyte antigen (HLA)-DR positive rate, immunoglobulins (IgA, IgG), etc. were persistently increased in both groups, reaching the peak values on the 7th day, and the indexes in high-energy EN group were significantly higher than those in the standard EN group [Alb (g/L): 36.43±5.81 vs. 33.79±5.34, PA (mg/L): 278.83±47.56 vs. 251.67±41.92, TRF (mg/L): 3.58±0.64 vs. 3.26±0.81, HLA-RD positive rate: (53.22±6.11)% vs. (50.21±5.69)%, IgA(mg/L): 165.34±40.13 vs. 141.54±38.76, IgG (mg/L): 4 990.68±881.66 vs. 4 211.75±861.54, all P < 0.05]. However, the levels of inflammatory factors such as C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α) in both groups were gradually decreased, reaching the valley values on the 7th day, and the indexes in high-energy EN group were significantly lower than those in the standard EN group [TNF-α(ng/L): 14.43±8.69 vs. 20.59±9.45, CRP (mg/L): 21.33±6.35 vs. 27.36±7.83, all P < 0.05]. Conclusion High energy EN not only can improve the nutritional status in patients with pulmonary heart failure, but also can reduce patients’ inflammation response and elevate their immune function.

Objective To investigate the effects of different early enteral nutrient (EN) emulsions of TPF-T and TP on nutritional status and intestinal mucosal barrier in patients with septic shock. Methods From May 2017 to May 2018, 112 patients with septic shock were continuously enrolled in the Department of Intensive Care Unit of the First People's Hospital of Taizhou, and they were randomly divided into a TPF-T group and TP group, each group with 56 cases. After admission, the patients in both groups were all treated according to the 2016 Saving Sepsis Campaign (SSC) Guidelines for septic shock. Both groups were supported with EN, TPT-T group was given TPF-T EN emulsion rich in fish oil, while TP group was supported with standard TP EN emulsion, and the therapeutic course was consecutive 7 days in both groups. The differences in nutritional status, inflammatory response, immune function, intestinal mucosal barrier, gastrointestinal symptoms and prognosis were compared between the two groups. Results After EN, the nutrition indicators such as albumin (Alb), prealbumin (PA), transferrin (TRF) and immune indexes (IgA, IgG), human leukocyte DR antigens (HLA-DR) and D-lactic acid were increased in both groups, reaching the peaks on the 7th day after EN application, Alb, PA, TRF, IgA, IgG, HLA-DR in the TPF-T group were significantly higher than those in the TP group [Alb (g/L): 34.43±5.81 vs. 33.59±5.34, PA (mg/L): 269.83±47.56 vs. 252.67±41.92, TRF (g/L): 3.43±0.64 vs. 3.32±0.81, IgA (mg/L): 159.45±34.56 vs. 143.31±33.81, IgG (mg/L): 4 947.68±871.66 vs. 4 583.75±841.54, HLA-DR: (68.22±9.11)% vs. (62.21±9.69)%], and after EN, the D-lactic acid in the TPF-T group was significantly lower than that in the TP group (mg/L: 30.42±6.79 vs. 33.34±7.31). The inflammatory indicators of tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), procalcitonin (PCT), endotoxin and diamine oxidase (DAO) were all gradually reduced in two groups, reached the lowest levels on the 7th day after EN application, and all the above-mentioned indicators in the TPF-T group were significantly lower than those in the TP group [TNF-α (ng/L):95.43±20.69 vs. 109.59±23.45, CRP (mg/L): 21.33±16.35 vs. 32.36±17.83, PCT (μg/L): 1.24±1.21 vs. 4.18±1.32, endotoxin (U/L): 10.32±2.31 vs. 11.54±2.69, DAO (g/L): 19.45±8.49 vs. 25.47±9.41]. The incidences of gastric retention, diarrhea and paralysis of lower digestive tract in TPF-T group were significantly lower than those in TP group [gastric retention: 14.29% (8/56) vs. 32.14% (18/56), diarrhea: 12.50% (7/56) vs. 35.71% (20/56), paralysis of lower digestive tract: 7.14% (4/56) vs. 23.21% (13/56)], the length of hospital stay was significantly shorter in the TPF-T group than that in the TP group (days: 18.77±5.08 vs. 21.71±6.67, P < 0.05); however, there was no significant difference in mortality between the two groups [14.29% (8/56) vs. 21.43% (12/56), P > 0.05]. Conclusion TPF-T could more effectively maintain nutritional status, reduce inflammatory reaction, improve immunity, protect intestinal mucosal barrier function, and has fewer adverse reactions, which was helpful to improve the prognosis of septic shock patients.