A statistical symptomatic evaluation on SAPHO syndrome from 56 cases of confirmed diagnosis and 352 cases of non-SAPHO involvement.

OBJECTIVE: To report a statistical evaluation of symptomatology based on 56 cases of SAPHO syndrome and 352 non-SAPHO involvement cases, to propose a symptomatic scoring system in consideration of early warning for SAPHO syndrome. METHODS: A cohort comprising 56 subjects diagnosed with SAPHO syndrome was reported, as well as 352 non-SAPHO involvement cases, including their chief complaints, skin manifestations, radiological findings, and laboratory tests. We systematically reviewed previous published five representative huge cohorts from different countries to conclude several specific features of SAPHO by comparing with our case series. The score of each specific index is based on respective incidence and comparison of two cohorts was performed. RESULT: In terms of complaint rates, all subjects of two cohorts suffered from osseous pain, which appeared in the anterior chest wall, spine, and limb which were calculated. In respect to dermatological lesions, SAPHO patients suffered from severe acne, and other patients (82.14%) accompanied with palmoplantar pustulosis. Having received radiological examinations, most SAPHO subjects rather than non-SAPHO involvement cases showed abnormal osteoarticular lesions under CT scanning and more detailed information under whole-body bone scintigraphy. Differences also emerged in elevation of inflammation values and rheumatic markers like HLA-B27. Based on our cases and huge cohorts documented, the early warning standard is set to be 5 scores. CONCLUSIONS: SAPHO syndrome case series with 56 subjects were reported and an accumulative scoring system for the early reminder on SAPHO syndrome was proposed. The threshold of this system is set to be 5 points. Key Points • Fifty-six patients diagnosed by SAPHO syndrome with detailed symptoms and radiological findings were reported. • Comparison was made between the 56 SAPHO patients and 352 non-SAPHO involvement cases. • An accumulative scoring system for the early reminder on SAPHO syndrome was proposed and the threshold of this system is set to be five points.

Photodynamic Modulation of Endoplasmic Reticulum and Mitochondria Network Boosted Cancer Immunotherapy.

Immunogenic cell death (ICD) represents a promising approach for enhancing tumor therapy efficacy by inducing antitumor immune response. However, current ICD inducers often have insufficient endoplasmic reticulum (ER) enrichment and ineffectiveness in tumor immune escape caused by ER-mitochondria interaction. In this study, a kind of photoactivatable probe, THTTPy-PTSA, which enables sequential targeting of the ER and mitochondria is developed. THTTPy-PTSA incorporates p-Toluenesulfonamide (PTSA) for ER targeting, and upon light irradiation, the tetrahydropyridine group undergoes a photo oxidative dehydrogenation reaction, transforming into a pyridinium group that acts as a mitochondria-targeting moiety. The results demonstrate that THTTPy-PTSA exhibits exceptional subcellular translocation from the ER to mitochondria upon light irradiation treatment, subsequently triggers a stronger ER stress response through a cascade-amplification effect. Importantly, the augmented ER stress leads to substantial therapeutic efficacy in a 4T1 tumor model by eliciting the release of numerous damage-associated molecular patterns, thereby inducing evident and widespread ICD, consequently enhancing the antitumor immune efficacy. Collectively, the findings emphasize the pivotal role of photodynamic modulation of the ER-mitochondria network, facilitated by THTTPy-PTSA with precise spatial and temporal regulation, in effectively bolstering the antitumor immune response. This innovative approach presents a promising alternative for addressing the challenges associated with cancer immunotherapy.

Comparison of characteristics and anti-MDA5 antibody distribution and effect between clinically amyopathic dermatomyositis and classic dermatomyositis: a retrospective case-control study.

Background: Clinically amyopathic dermatomyositis (CADM) is a distinct subtype of dermatomyositis (DM) characterized by typical DM cutaneous findings but with minimal or no evidence of myositis. It possesses unique features different from classic DM (CDM). Anti-melanoma differentiation-associated gene 5 (MDA5) antibodies were found in CADM and are thought to increase the risk of rapidly progressive interstitial lung disease (RP-ILD) and are present in both CADM and CDM patients, affecting their condition and prognosis. Nevertheless, no large-sample studies have compared all aspects concerning patients with CADM and those with CDM. This study aimed to investigate differences in clinical characteristics and risk factors for mortality between CADM and CDM and to clarify the distribution and impact of anti-MDA5 antibodies in patients with these conditions. Methods: A retrospective case-control study included 330 patients and collected and analyzed their clinical data from The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Hospital of Traditional Chinese Medicine between January 2015 and July 2022; all patients were followed up to evaluate changes in their condition and prognosis. Several new cohorts were designed around anti-MDA5 antibodies to explore their distribution and impact in CADM and CDM. Results: We found CADM to be associated with higher rates of mortality, 1-year mortality, interstitial lung disease (ILD), and RP-ILD than CDM. In CADM, RP-ILD, anti-MDA5 antibodies, and high ferritin and lactate dehydrogenase (LDH) levels were identified as independent risk factors for death. In CDM, the neutrophil-to-lymphocyte ratio, anti-MDA5 antibodies, and high ferritin levels were shown to be independent risk factors for death, whereas mechanic's hand was considered a protective factor against it. Anti-MDA5 antibody-positive patients did not exhibit any significant difference based on whether they belonged to the CADM or CDM groups. When no anti-MDA5 antibody-positive patients participated, the ferritin levels and rates of RP-ILD and ILD were still higher in CADM than in CDM; however, such differences decreased, whereas the LDH levels, rates of mortality, and 1-year mortality did not differ. Anti-MDA5 antibody-positive patients consistently showed higher LDH and ferritin levels, lower lymphocyte levels, higher probability of RP-ILD and ILD, and worse prognosis than anti-MDA5 antibody-negative patients, irrespective of whether the patients had DM, CADM, or CDM. Conclusion: Patients with CADM exhibit relatively worse symptoms, serological findings, and prognosis than those with CDM. Furthermore, patients with CADM and those with CDM have commonalities and differences in risk factors for death. Moreover, CADM may necessitate earlier and more aggressive treatment strategies than CDM. Anti-MDA5 antibodies occur at a high level in patients with CADM, not only affecting the symptoms and prognosis of DM but also having a non-negligible impact on the differences between CADM and CDM. Hence, screening for anti-MDA5 antibodies in patients with CADM and CDM is extremely essential.

A New Dual-Input Deep Anomaly Detection Method for Early Faults Warning of Rolling Bearings.

To address the problem of low fault diagnosis accuracy caused by insufficient fault samples of rolling bearings, a dual-input deep anomaly detection method with zero fault samples is proposed for early fault warning of rolling bearings. First, the main framework of dual-input feature extraction based on a convolutional neural network (CNN) is established, and the two outputs of the main frame are subjected to the autoencoder structure. Then, the secondary feature extraction is performed. At the same time, the experience pool structure is introduced to improve the feature learning ability of the network. A new objective loss function is also proposed to learn the network parameters. Then, the vibration acceleration signal is preprocessed by wavelet to obtain multiple signals in different frequency bands, and the two signals in the high-frequency band are two-dimensionally encoded and used as the network input. Finally, the unsupervised learning of the model is completed on five sets of actual full-life rolling bearing fault data sets relying only on some samples in a normal state. The verification results show that the proposed method can realize earlier than the RMS, Kurtosis, and other features. The early fault warning and the accuracy rate of more than 98% show that the method is highly capable of early fault warning and anomaly detection.

Photoactivatable Sequential Destruction of Multiorganelles for Cancer Therapy.

Organelle-targeted therapy guided by fluorescence imaging is promising for precise cancer treatment. However, most current organelle-targeted therapeutics can only destruct single organelles, which suffer from limited therapeutic efficacy. To address this challenge, a photoactivatable probe was developed for sequential photodynamic destruction of multiorganelles in cancer cells, including lysosomes, lipid droplets, and mitochondria. This photoactivatable probe not only exhibits efficient cancer cell eradication in vitro but also can suppress tumor growth in vivo. Simultaneously, the photoactivatable probe enables sequential destruction of multiple organelles in cancer cells, which can be observed in situ through the conversion of green-to-red fluorescence facilitated by a photooxidative dehydrogenation reaction. We believe this photoactivatable probe for sequential destruction of multiple organelles associated with fluorescence color conversion provides a new strategy for cancer treatment with greatly improved efficacy.

Exceptional response of skin symptoms to secukinumab treatment in a patient with SAPHO syndrome: Case report and literature review.

RATIONALE: SAPHO syndrome is a rare clinical entity characterized by a wide range of dermatological and musculoskeletal manifestations. Treatment strategies are not standardized. Palmoplantar pustulosis (PPP) is the most common rash in patients with SAPHO syndrome. PATIENT CONCERNS: A 24-year-old Chinese woman with no relevant medical or familial history had a 1-year history of cutaneous lesions with PPP and pain in the sternoclavicular joint. DIAGNOSIS: Based on the diagnostic criteria for SAPHO syndrome proposed by Nguyen et al in 2012, we diagnosed SAPHO syndrome with severe PPP as the predominant manifestation. INTERVENTIONS: Due to the limited therapeutic efficacy of methotrexate and cyclosporin, we started therapy with subcutaneous secukinumab 150 mg weekly for the first month, then 150 mg monthly thereafter. OUTCOMES: After 4 weeks of secukinumab administration, the patient showed significant remission of pustular skin lesions, with almost no joint pain and no adverse reaction. Complete remission of skin symptoms was achieved after 3 months. Joint pain and adverse events have not reoccurred in follow-up thus far. CONCLUSIONS: In patients with SAPHO syndrome, we recommend personalized treatment, which may have excellent therapeutic efficacy in those with PPP or severe skin symptoms. Although data related to the use of IL-17 blockers for SAPHO syndrome are very limited, secukinumab provides a novel therapeutic option, especially for patients with PPP and severe skin lesions. Further prospective studies are needed to support our findings.

Pancreatic carcinoma presented with panniculitis and polyarthritis: A rare case.

Extrapancreatic manifestations can complicate pancreatic disorders. Pancreatic panniculitis, characterized by subcutaneous fat necrosis, develops in 0.3%-3% of patients with pancreatic disorders. Occasionally, pancreatic panniculitis and polyarthritis occur in the same patient with pancreatic diseases, a rare symptomatic triad known as pancreatitis, panniculitis, and polyarthritis (PPP) syndrome. PPP syndrome is primarily caused by acute or chronic pancreatitis and pancreatic carcinoma. Almost half of the patients with PPP syndrome do not present with gastrointestinal signs, which may lead to a delayed diagnosis of underlying pancreatic disease. The skin and arthritic symptoms may be mistaken for rheumatic diseases. The histological finding of skin lesions is a valuable clue for diagnosing pancreatic diseases. Due to the high mortality rate when PPP syndrome is associated with pancreatic carcinoma, we highlight that the pancreas should be thoroughly examined if a skin biopsy indicates pancreatic panniculitis.

Secondary angle-closure glaucoma as an ocular presentation of systemic lupus erythematosus: a case report.

Systemic lupus erythematosus (SLE) is a chronic idiopathic autoimmune disease. SLE can involve almost any part of the eyes. However, bilateral angle-closure glaucoma due to lupus choroidopathy that is accompanied by polyserositis and nephropathy is rare. We report a 21-year-old woman whose clinical manifestations were diagnosed as bilateral angle-closure glaucoma caused by ciliochoroidal effusion. Subsequently, SLE and lupus nephritis were diagnosed on the basis of malar rash, photosensitivity, proteinuria, positive anti-Smith and anti-DNA antibodies, and a renal histopathological biopsy. After 1 month of treatment with steroids and immunosuppressive drugs, the patient's intraocular pressure returned to normal, visual acuity improved, and lupus nephritis was effectively controlled. Bilateral secondary acute angle closure caused by SLE choroidal disease can be an ocular manifestation of SLE, and is usually accompanied by polyserositis and nephropathy. High-dose steroids and immunosuppressive therapy should be immediately and actively provided for this condition.

Effector T helper cell populations are elevated in the bone marrow of rheumatoid arthritis patients and correlate with disease severity.

This study is to investigate the frequencies of T-helper (Th)22, Th17 and Th1 cells and the levels of related cytokines in subchondral bone marrow in patients with rheumatoid arthritis (RA). Bone marrow and peripheral blood samples were collected from RA, osteoarthritis (OA) patients and healthy controls. The frequencies of Th22, Th17, and Th1 cells were examined by flow cytometry. Levels of interleukin (IL)-22, IL-17 and IFN-γ were examined by ELISA. Disease Activity Score in 28 joints (DAS28) of RA patients were analyzed. Bone marrow Th22, Th17 and Th1 cells in RA patients were markedly increased comparing to OA or healthy controls. Each T cell subset in bone marrow was elevated comparing with that in the peripheral blood in RA patients. Consistently, plasma levels of IL-22 and IL-17 were elevated in RA patients, and the elevation was more notable in the bone marrow than in the peripheral blood. Additionally, the percentages of Th22, Th17 and Th1 cells as well as the levels of IL-22 and IL-17 in bone marrow were positively correlated with DAS28. These results suggest that local pro-inflammatory Th cells are elevated in bone marrow, which may play an important role in situ in RA and contribute to the pathogenesis of in RA.

Tim3+ Foxp3 + Treg Cells Are Potent Inhibitors of Effector T Cells and Are Suppressed in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder. Earlier studies have demonstrated that regulatory T (Treg) cells, the main cell type mediating immune tolerance, appeared to be enriched in the inflamed synovial tissues. It is still unclear why the Treg cells in RA patients are unable to limit exacerbated inflammation. Here, we found that the frequency of Tim3+Foxp3+ Treg cells, which were potent suppressors of proinflammatory responses, was downregulated in RA patients. Reduction in Tim3+Foxp3+ Treg frequency was correlated with increased RA disease activity. Furthermore, we observed that Tim3+Foxp3+ Tregs were expressed more interleukin (IL)-10 than Tim3-Foxp3+ Tregs. CD4+CD25+Tim3+ T cells had higher capability of inhibiting interferon (IFN)-γ and tumor necrosis factor (TNF)-α secretion from T cells and peripheral blood mononuclear cells (PBMCs) than CD4+CD25+Tim3- T cells. Compared to that in healthy individuals, CD4+CD25+ T cells in RA patients were less potent in suppressing IFN-γ and TNF-α production from PBMCs. Blocking Tim3 on CD4+CD25+ T cells from healthy controls resulted in an elevation of IFN-γ and TNF-α production from PBMCs, suggesting that Tim3 expression on CD4+CD25+ T cells was required for optimal Treg function. However, this phenomenon was not observed in RA patients. In conclusion, our study suggested that the CD4+CD25+Foxp3+ Treg cells from RA patients demonstrated a reduction of Tim3 and were less functional than Treg cells from healthy controls in a Tim3-related manner.

Electroacupuncture combined with mosapride alleviates symptoms in diabetic patients with gastroparesis.

The present study compared the clinical effectiveness of electroacupuncture (EA), monotherapy and combination therapy involving the administration of EA and mosapride in diabetic patients with severe or mild symptoms suggestive of gastroparesis. A total of 56 patients with type 2 diabetes who had symptoms suggestive of gastroparesis for >3 months were divided into two groups according to the Gastroparesis Cardinal Symptom Index (GCSI) score, including 33 in the mild group (GCSI score <3.5) and 23 in the severe group (GCSI score ≥3.5). Initially, all patients received EA monotherapy for 14 days. An effective response was defined as a reduction of the overall baseline GCSI score by >25% after treatment. The non-responding patients then received a combination treatment with EA and mosapride. Gastric emptying was assessed by the 13C-octanoic acid breath test at the beginning and end of each treatment session. Two patients in the severe group dropped out of the study during the initial treatment session. The results revealed that 34 early-responding patients (30 from the mild group and 4 from the severe group) treated with EA monotherapy, and 20 non-early-responding patients receiving combination therapy with EA and mosapride showed clinically significant improvements. Analysis of data from the mild subgroup demonstrated that EA treatment specifically improved symptoms of nausea, vomiting, stomach fullness, excessive fullness and bloating. There was no statistically significant difference in the gastric half-emptying time among patients prior to and after EA monotherapy. These preliminary results suggested that EA may be an option for improving mild symptoms in patients with diabetic gastroparesis, whereas combination therapy involving EA and pharmaceutics is required in patients with severe symptoms.

Low-frequency electrical stimulation induces the proliferation and differentiation of peripheral blood stem cells into Schwann cells.

BACKGROUND: Functional recovery after peripheral nerve injury remains a tough problem at present. Specifically, a type of glial cell exists in peripheral nerves that promotes axonal growth and myelin formation and secretes various active substances, such as neurotrophic factors, extracellular matrix and adherence factors. These substances have important significance for the survival, growth and regeneration of nerve fibers. Numerous recent studies have shown that electrical stimulation can increase the number of myelinated nerve fibers. However, whether electrical stimulation acts on neurons or Schwann cells has not been verified in vivo. This study investigates low-frequency electrical stimulation-induced proliferation and differentiation of peripheral blood stem cells into Schwann cells and explores possible mechanisms. METHODS: Peripheral blood stem cells from Sprague-Dawley rats were primarily cultured. Cells in passage 3 were divided into 4 groups: a low-frequency electrical stimulation group (20 Hz, 100 µs, 3 V), a low-frequency electrical stimulation+PD98059 (blocking the extracellular signal-regulated kinase [ERK] signaling pathway) group, a PD98059 group and a control group (no treatment). After induction, the cells were characterized. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazoliumbromide assay was employed to measure the absorbance values at 570 nm in the 4 groups. A Western blot assay was used to detect the expression of cyclin D1 and cyclin-dependent kinase 4 (CDK4) in each group. RESULTS: No significant difference in cell viability was detected before induction. Peripheral blood stem cells from the 4 groups differentiated into Schwann cells. Phosphorylated ERK 1/2, cyclin D1 and CDK4 protein levels were highest in the low-frequency electrical stimulation group and lowest in the ERK blockage group. Phosphorylated ERK 1/2, cyclin D1 and CDK4 protein levels in the low-frequency electrical stimulation+ERK blockage group were lower than those in the low-frequency electrical stimulation group but higher than those in the ERK blockage group. CONCLUSIONS: Low-frequency electrical stimulation contributed to the proliferation of peripheral blood stem cells cultured in vitro and induced differentiation into Schwann cells. The ERK signaling pathway underlies cell proliferation and differentiation.

Effects of electroacupuncture combined with clean intermittent catheterization on urinary retention after spinal cord injury: a single blind randomized controlled clinical trial.

PURPOSE: This study aimed to evaluate the therapeutic effects of electroacupuncture (EA) combined with clean intermittent catheterization (CIC) on spinal cord injury (SCI) induced urinary retention. METHODS: A total of 107 patients with SCI induced urinary retention were randomly divided into 3 groups, including group 1 (CIC treatment), group 2 (EA combined with CIC treatment), and group 3 (sham acupuncture combined with CIC treatment). After different treatments, the residual urine volume, voided volume (each time), number of bladder balance patients, and frequency of CIC were recorded and compared. RESULTS: There were no significant differences between group 1 and 3 in number of bladder balance patients and voided volume (ml) at the 1(st) month. The rate of patients reaching bladder balance was significantly higher in group 2 than group 1 and 3 (P<0.05). The frequency of CIC was significantly less in group 2 than the other groups (P<0.001). The voided volume at the 1(st) and the 3(rd) month after surgery was significantly higher in group 2 than that in group 1 and 3 (P<0.001). Meanwhile, after 1 month and 3 months of treatment, residual urine volume was significantly reduced in group 2 compared with that in group 1 and 3 (P<0.001). CONCLUSION: The therapeutic effects of EA were effective for SCI induced urinary retention by reducing residual urine volume and the frequency of CIC, increasing voided volume, and promoting the balance of vesical function.

Diagnostic value of anti-Sa and anticitrullinated protein antibodies in rheumatoid arthritis.

OBJECTIVE: To determine the diagnostic value of anticitrullinated protein antibodies, second generation (ACPA2), by electrochemiluminescent immunoassay (ECLIA) and anti-Sa by ELISA in a large cohort of Chinese patients with early rheumatoid arthritis (RA). METHODS: One hundred ninety-eight patients with early RA (< 1 yr duration), 112 with other rheumatic diseases, and 60 healthy individuals were studied. RESULTS: The combination of anti-Sa and ACPA2 positivity had the highest specificity (99.42%), but it had a rather low sensitivity (50.0%). The combination of anti-rheumatoid factor (RF) and ACPA2 showed the highest sensitivity (80.30%), with specificity of 95.93%. The mean titer of ACPA2 and RF was significantly higher in the anti-Sa-positive group compared to the negative group (ACPA2, p <0.001; RF, p = 0.007). The 28-joint Disease Activity Scores of the anti-Sa-positive patients were significantly higher than those of the negative group (p = 0.01). The anti-Sa had no significant correlation with age, sex, antinuclear antibody, SSA, SSB, erythrocyte sedimentation rate, C-reactive protein, immunoglobulin A (IgA), IgG, IgM, C3, and C4. CONCLUSION: Our results come from a newly developed ECLIA for detection of ACPA2 and the anti-Sa-antibody-based ELISA system. The combined application of ACPA2 and anti-Sa tests can improve the laboratory diagnosis of early RA.