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Osteoarthritis, as a degenerative disease, is a common problem and results in high socioeconomic costs and rates of disability. The most commonly affected joint is the knee and characterized by progressive destruction of articular cartilage, loss of extracellular matrix, and progressive inflammation. Mesenchymal stromal cell (MSC)-based therapy has been explored as a new regenerative treatment for knee osteoarthritis in recent years. However, the detailed functions of MSC-based therapy and related mechanism, especially of cartilage regeneration, have not been explained. Hence, this review summarized how to choose, authenticate, and culture different origins of MSCs and derived exosomes. Moreover, clinical application and the latest mechanistical findings of MSC-based therapy in cartilage regeneration were also demonstrated.

Background In gut microbiome studies, the cultured gut microbial resource plays essential roles, such as helping to unravel gut microbial functions and host-microbe interactions. Although several major studies have been performed to elucidate the cultured human gut microbiota, up to 70% of the Unified Human Gastrointestinal Genome species have not been cultured to date. Large-scale gut microbial isolation and identification as well as availability to the public are imperative for gut microbial studies and further characterizing human gut microbial functions. Results In this study, we constructed a human Gut Microbial Biobank (hGMB; homepage: hgmb.nmdc.cn ) through the cultivation of 10,558 isolates from 31 sample mixtures of 239 fresh fecal samples from healthy Chinese volunteers, and deposited 1170 strains representing 400 different species in culture collections of the International Depository Authority for long-term preservation and public access worldwide. Following the rules of the International Code of Nomenclature of Prokaryotes, 102 new species were characterized and denominated, while 28 new genera and 3 new families were proposed. hGMB represented over 80% of the common and dominant human gut microbial genera and species characterized from global human gut 16S rRNA gene amplicon data ( n = 11,647) and cultured 24 “most-wanted” and “medium priority” taxa proposed by the Human Microbiome Project. We in total sequenced 115 genomes representing 102 novel taxa and 13 previously known species. Further in silico analysis revealed that the newly sequenced hGMB genomes represented 22 previously uncultured species in the Unified Human Gastrointestinal Genome (UHGG) and contributed 24 representatives of potentially “dark taxa” that had not been discovered by UHGG. The nonredundant gene catalogs generated from the hGMB genomes covered over 50% of the functionally known genes (KEGG orthologs) in the largest global human gut gene catalogs and approximately 10% of the “most wanted” functionally unknown proteins in the FUnkFams database. Conclusions A publicly accessible human Gut Microbial Biobank (hGMB) was established that contained 1170 strains and represents 400 human gut microbial species. hGMB expands the gut microbial resources and genomic repository by adding 102 novel species, 28 new genera, 3 new families, and 115 new genomes of human gut microbes. 6-6epGnHGpob5sGsfPZJHQ Video abstract

Background Exoskeleton-assisted walking (EAW) is expected to improve the gait of spinal cord injury (SCI) individuals. However, few studies reported the changes of pulmonary function (PF) parameters after EAW trainings. Hence, we aimed to explore the effect of EAW on PF parameters, 6-min walk test (6MWT) and lower extremity motor score (LEMS) in individuals with SCI and to compare those with conventional trainings. Methods In this prospective, single-center, single-blinded randomized controlled pilot study, 18 SCI participants were randomized into the EAW group (n = 9) and conventional group (n = 9) and received 16 sessions of 50–60 min training (4 days/week, 4 weeks). Pulmonary function parameters consisting of the forced vital capacity (FVC), forced expiratory volume in 1 s (FEV 1 ), forced expiratory flow (FEF), peak expiratory flow, and maximal voluntary ventilation, 6MWT with assisted devices and LEMS were reported pre- and post-training. Results Values of FVC (p = 0.041), predicted FVC% (p = 0.012) and FEV 1 (p = 0.013) were significantly greater in EAW group (FVC: 3.8 ± 1.1 L; FVC% pred  = 94.1 ± 24.5%; FEV 1 : 3.5 ± 1.0 L) compared with conventional group (FVC: 2.8 ± 0.8 L; FVC% pred  = 65.4 ± 17.6%; FEV 1 : 2.4 ± 0.6 L) after training. Participants in EAW group completed 6MWT with median 17.3 m while wearing the exoskeleton. There was no difference in LEMS and no adverse event. Conclusions The current results suggest that EAW has potential benefits to facilitate PF parameters among individuals with lower thoracic neurological level of SCI compared with conventional trainings. Additionally, robotic exoskeleton helped walking. Trial registration : Registered on 22 May 2020 at Chinese Clinical Trial Registry (ChiCTR2000033166). http://www.chictr.org.cn/edit.aspx?pid=53920&htm=4 .

Background Myofascial pain syndrome (MPS) is a regional musculoskeletal pain associated with myofascial trigger point (MTrP), lacks therapies with sustained efficacy. Current modalities offer short-term relief but fail to address underlying tissue degeneration. Objectives This study aimed to evaluate the 3-month safety and efficacy of ultrasound-guided platelet-rich plasma (PRP) injections in alleviating MPS-related pain and function. Methods From January 2023 to April 2023, we selected 71 eligible individuals with MPS who received PRP treatment of the upper trapezius, rhomboid, erector spinae, and quadratus lumborum in the Department of Rehabilitation Medicine, West China Hospital, Sichuan University, a retrospective case series study. Primary outcome was pain quantified by the Visual Analog Scale (VAS) and the McGill Pain Questionnaire (McGill). Secondary outcomes were region-specific functional improvement evaluated using the Neck Disability Index (NDI) for cervical pathology and the Oswestry Disability Index (ODI) for lumbar conditions, with additional assessment via the Roland Morris Disability Questionnaire (RMDQ), and quality of life measured by the Medical Outcomes Short Form-36 (SF-36). These parameters were evaluated at baseline and 24 h, 2 weeks, 1 month, and 3 months post-treatment. Results The cohort included 71 individuals (mean age 47.6 ± 15.9 years; 71.8% female) with chronic MPS. The pain VAS decreased from 5.0 [4.0–6.0] at baseline to 1.0 [1.0–2.0] at 3 months ( p  < 0.001), with the McGill decreased from 11.0 [8.0–15.0] to 2.0 [2.0–5.0] ( p  < 0.001). The NDI decreased from 42.0 [29.3–53.3] at baseline to 9.5 [5.0–11.0] ( p  < 0.001). The ODI declined from 22.0 [14.0–29.0] to 10.0 [6.0–14.0] ( p  < 0.001). The RMDQ showed improvement, from 10.0 [6.5–16.0] to 4.0 [2.0–5.0] ( p  < 0.001). Similarly, the SF-36 score was obviously improved 3 months post-treatment of PRP ( p  < 0.01). No adverse reactions were reported during follow-up. Conclusion Ultrasound-guided platelet-rich plasma treatment could significantly alleviate the pain and improve the physical function and quality of life in the individuals with myofascial pain syndrome during 3-months follow-up.

Study designA pre-post observational study.ObjectivesTo evaluate the safety and feasibility of a new rehabilitation robotic device for assisting individuals with lower extremity motor complete lesions following spinal cord injury (SCI).SettingThree hospitals in Sichuan Province, China.MethodsIndividuals aged 15–75 years with an SCI between vertebrae six (T6) and lumbar 1 (L1) and complete motor paralysis participated in an exoskeletal-assisted walking (EAW) programme (2 weeks, 5 days/week, 30 min/day). Data were collected pre-, mid- (week 1) and post-intervention (week 2).ResultsTwenty-eight individuals (mean age = 41.3, 71% males) participated in the EAW programme. The distance walked during the 6-min walking test (6MWT) increased relative to that at baseline, during week 1 (13.0 ± 5.3 m) and week 2 (16.2 ± 5.3 m) when wearing the exoskeleton. The walking speed during the 10-m walking test (10MWT) increased from 0.039 ± 0.016 to 0.045 ± 0.016 m/s. The Hoffer walking ability grade, the Spinal Cord Independence Measure (SCIM), and the Walking Index for SCI II (WISCI II) changed after 2 weeks of EAW. No improvement in lower extremity motor score (LEMS) was observed. The rates of adverse events and serious adverse events were 21% and 4%, respectively.ConclusionsThe EAW programme with the new robotic exoskeleton provided potential meaningful improvements in mobility for individuals with SCI and had few adverse events.

Osteonecrosis of the femoral head (ONFH) is a refractory orthopedic disease in which steroids may induce bone cell necroptosis. Extracellular vesicles derived from bone marrow mesenchymal stromal cells (BMSC-EVs) are recognized as novel therapies to improve ONFH. Pulsed electromagnetic fields (PEMFs) increase the paracrine activity of BMSCs. Nonetheless, the effect and mechanism of PEMFs preconditioned BMSC-EVs (BMSC-EVs ) for treating ONFH are unclear. The BMSC-EVs with different magnetic amplitudes were incubated with dexamethasone-induced MC3T3-E1 cells and the osteogenic differentiation and necroptosis were observed. Furthermore, RNA sequencing of MC3T3-E1 cells incubated with incubated with PEMFs of a specific amplitude or without PEMFs was conducted to identify potential mechanisms involved. Reverse transcription‒quantitative polymerase chain reaction (RT-qPCR), immunofluorescence and Western blotting were performed to detect necroptosis-related pathways. SD rats receiving steroid injections were randomly assigned to receive PBS, BMSC-EVs or BMSC-EVs therapy. Micro-CT scan, histological, and immunohistochemical analyses were used to evaluate the therapeutic effects on bone formation and necroptosis of the femoral head in ONFH animals. The characteristics of the BMSC-EVs were similar to those of the BMSC-EVs. , co-culture of osteoblasts and PEMFs with 3 millitesla (mT) amplitude preconditioned BMSC-EVs (BMSC-EVs promoted osteogenic differentiation and inhibited cell death. The results of RNA sequencing revealed that the expression of Ripk3 was significantly lower in the BMSC-EVs group than in the BMSC-EVs group. RT-qPCR, immunofluorescence and Western blotting revealed that the expression of necroptosis-related molecules (RIPK1, RIPK3, and MLKL) was suppressed in BMSC-EVs group ( < 0.05). , the BMSC-EVs group presented better bone morphology of the femoral head via micro-CT, with a lower protein expression of MLKL and a higher expression of RUNX2 ( < 0.05) at 2 weeks, while lower expressions of RIPK1 and RIPK3, and higher levels of RUNX2 and OCN ( < 0.05) at the femoral head at 6 weeks after injection than did the BMSCs-EVs group. PEMFs with 3 mT amplitude preconditioned BMSC-EVs could promote bone formation by inhibiting osteoblasts necroptosis via Ripk1-Ripk3-Mlkl signaling in ONFH.

Background Platelet-rich plasma (PRP) contains various growth factors and inflammatory regulators, which can effectively reduce inflammation in joints and promote tissue repair. Multiple studies have proved its effectiveness in the treatment of knee osteoarthritis (KOA). Low-intensity focused ultrasound (LIFU) and transcutaneous electrical nerve stimulation (TENS) are non-invasive and safe physical therapy methods for KOA. This study is the first to propose the treatment of KOA with physical stimulation after PRP treatment, and to observe the clinical efficacy of the treatment method. Methods This is a protocol paper that outlines a randomized controlled trial, patients will be assigned randomly to the PRP group, PRP+LIFU group, PRP+TENS group, and PRP+LIFU combined TENS group. The patients will be followed at 12-week and 24-week time points to evaluate the primary and secondary outcomes of the study. The primary outcome is the VAS pain score. Secondary outcomes include Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and International Knee Documentation Committee scores (IKDC). After baseline examination, all patients will sign a written informed consent for study participation after a full explanation of the treatment protocol. We have planned a total of 120 patients (30 patients per group). Discussion The objective of this clinical trial is to evaluate the effect of different physical stimulation after PRP treatment for KOA. The data will be published after the completion of the study. Trial registration This study has been registered with the Chinese Clinical Trials Registry. Registration number: ChiCTR2200065119 (registered date: 10/28/2022).

Abstract Background Streptococcus dysgalactiae subsp. dysgalactiae has been identified as an animal pathogen that is thought to occur only in animal populations. Between 2009 and 2022, humans infected with SDSD were reported rarely. There is a lack of details on the natural history, clinical features, and management of disease caused by this pathogen. This case outlines a human SDSD with muscle aches and progressive loss of muscle strength leading to immobility and multi-organ dysfunction syndrome. Case presentation She presented with muscle pain and weakness, and later developed a sore throat, headache and fever with a maximum temperature of 40.5 °C. The muscle strength of the extremities gradually decreased to grade 1 and the patient was unable to move on his own. Next-generation blood sequencing and multi-culture confirmed the presence of Streptococcus dysgalactiae and Streptococcus dysgalactiae subsp. Dysgalactiae, respectively. A Sequential Organ Failure Assessment score of 6 indicated septicemia, and therapeutic antibiotics were prescribed empirically. After 19 days of inpatient treatment, the patient's condition greatly improved and completely recovered within a month. Conclusion Symptoms of Streptococcus dysgalactiae subsp. dysgalactiae presenting with progressive limb weakness resemble polymyositis, so a precise differential diagnosis is essential. Multidisciplinary consultation is helpful when polymyositis cannot be ruled out and facilitates the choice of an optimal treatment protocol. In the context of this case, penicillin is an effective antibiotic for Streptococcus dysgalactiae subsp. dysgalactiae infection.

Background Streptococcus dysgalactiae subsp. dysgalactiae has been identified as an animal pathogen that is thought to occur only in animal populations. Between 2009 and 2022, humans infected with SDSD were reported rarely. There is a lack of details on the natural history, clinical features, and management of disease caused by this pathogen. This case outlines a human SDSD with muscle aches and progressive loss of muscle strength leading to immobility and multi-organ dysfunction syndrome. Case presentation She presented with muscle pain and weakness, and later developed a sore throat, headache and fever with a maximum temperature of 40.5 °C. The muscle strength of the extremities gradually decreased to grade 1 and the patient was unable to move on his own. Next-generation blood sequencing and multi-culture confirmed the presence of Streptococcus dysgalactiae and Streptococcus dysgalactiae subsp. Dysgalactiae, respectively. A Sequential Organ Failure Assessment score of 6 indicated septicemia, and therapeutic antibiotics were prescribed empirically. After 19 days of inpatient treatment, the patient's condition greatly improved and completely recovered within a month. Conclusion Symptoms of Streptococcus dysgalactiae subsp. dysgalactiae presenting with progressive limb weakness resemble polymyositis, so a precise differential diagnosis is essential. Multidisciplinary consultation is helpful when polymyositis cannot be ruled out and facilitates the choice of an optimal treatment protocol. In the context of this case, penicillin is an effective antibiotic for Streptococcus dysgalactiae subsp. dysgalactiae infection.