BACKGROUND: Macrophage polarization anomalies and dysfunction play a crucial role in the pathogenesis of immune thrombocytopenia (ITP). Itaconate is a Krebs cycle-derived immunometabolite synthesized by myeloid cells to modulate cellular metabolism and inflammatory responses. This study aimed to evaluate the immunoregulatory effects of an itaconate derivative on macrophages in patients with ITP. METHODS: Peripheral blood-derived macrophages from patients with ITP and healthy controls were treated with 4-octyl itaconate (4-OI), a derivative of itaconate that can penetrate the cell membrane. Macrophage polarization, antigen-presenting functions, and phagocytic capability were measured via flow cytometry and enzyme-linked immunosorbent assay (ELISA). Macrophage glycolysis in patients with ITP and the metabolic regulatory effect of 4-OI were detected using a Seahorse XFe96 Analyzer. An active murine model of ITP was used to evaluate the therapeutic effects of 4-OI in vivo . RESULTS: 4-OI reduced the levels of CD80 and CD86 in M1 macrophages and suppressed the release of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 pro-inflammatory cytokines, suggesting that 4-OI could hinder the polarization of macrophages toward an M1 phenotype. We found that 4-OI pretreated M1 macrophages reduced the proliferation of CD4 + T cells and promoted the differentiation of regulatory T cells. In addition, after 4-OI treatment, the phagocytic capacity of M1 macrophages toward antibody-coated platelets decreased significantly in patients with ITP. In addition, the glycolytic function of M1 macrophages was elevated in individuals with ITP compared to those in healthy controls. 4-OI treatment downregulated glycolysis in M1 macrophages. The glycolysis inhibitor 2-deoxy-d-glucose (2-DG) also inhibited the polarization of M1 macrophages and restored their functions. In vivo , 4-OI treatment significantly increased platelet counts in the active ITP murine model. CONCLUSIONS Itaconate derivative 4-OI inhibited M1 macrophage polarization and restored impaired functions through metabolic reprogramming. This study provides a novel therapeutic option for ITP.
Macrophages/metabolism* ; Humans ; Animals ; Succinates/pharmacology* ; Mice ; Male ; Female ; Adult ; Middle Aged ; Flow Cytometry ; Tumor Necrosis Factor-alpha/metabolism* ; Enzyme-Linked Immunosorbent Assay ; Purpura, Thrombocytopenic, Idiopathic/metabolism* ; Glycolysis/drug effects* ; Metabolic Reprogramming

Syringa pinnatifolia, belonging to the family Oleaceae, is a species endemic to China. It is predominantly distributed in the Helan Mountains region of Inner Mongolia and Ningxia of China. The peeled roots, stems, and thick branches have been used as a distinctive Mongolian medicinal material known as "Shan-chen-xiang", which has effects such as suppressing "khii", clearing heat, and relieving pain and is employed for the treatment of cardiovascular and pulmonary diseases and joint pain. Over the past five years, significant increase was achieved in research on chemical constituents and pharmacological effects. There were a total of 130 new constituents reported, covering sesquiterpenoids, lignans, and alkaloids. Its effects of anti-myocardial ischemia, anti-cerebral ischemia/reperfusion, sedation, and analgesia were revealed, and the mechanisms of agarwood formation were also investigated. To better understand its medical value and potential of clinical application, this review updates the research progress in recent five years focusing on the chemical constituents and pharmacological effects of S. pinnatifolia, providing reference for subsequent research on active ingredient and support for its innovative application in modern medicine system.
Medicine, Mongolian Traditional ; Humans ; Drugs, Chinese Herbal/pharmacology* ; Animals ; Syringa/chemistry*

OBJECTIVE: To examine the effectiveness of Chinese medicine (CM) Lianhua Qingwen Granule (LHQW) and Jingyin Gubiao Prescription (JYGB) in asymptomatic or mild patients with Omicron infection in the shelter hospital. METHODS: This single-center retrospective cohort study was conducted in the largest shelter hospital in Shanghai, China, from April 10, 2022 to May 30, 2022. A total of 56,244 asymptomatic and mild Omicron cases were included and divided into 4 groups, i.e., non-administration group (23,702 cases), LHQW group (11,576 cases), JYGB group (12,112 cases), and dual combination of LHQW and JYGB group (8,854 cases). The length of stay (LOS) in the hospital was used to assess the effectiveness of LHQW and JYGB treatment on Omicron infection. RESULTS: Patients aged 41-60 years, with nadir threshold cycle (C_T) value of N gene <25, or those fully vaccinated preferred to receive CM therapy. Before or after propensity score matching (PSM), the multiple linear regression showed that LHQW and JYGB treatment were independent influence factors of LOS (both P<0.001). After PSM, there were significant differences in LOS between the LHQW/JYGB combination and the other groups (P<0.01). The results of factorial design ANOVA proved that the LHQW/JYGB combination therapy synergistically shortened LOS (P=0.032). CONCLUSIONS Patients with a nadir C_T value <25 were more likely to accept CM. The LHQW/JYGB combination therapy could shorten the LOS of Omicron-infected individuals in an isolated environment.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Female ; Middle Aged ; Adult ; China/epidemiology* ; Hospitalization ; COVID-19 Drug Treatment ; COVID-19/epidemiology* ; SARS-CoV-2 ; Retrospective Studies ; Treatment Outcome ; Length of Stay ; Young Adult ; Aged

OBJECTIVE: To evaluate the protective effects of gentiopicroside (GPS) against reactive oxygen species (ROS)-induced NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation in endothelial cells, aiming to reduce atherosclerosis. METHODS: Eight-week-old male ApoE-deficient mice were randomly divided into 2 groups (n=10 per group): the vehicle group and the GPS treatment group. Both groups were fed a high-fat diet for 16 weeks. GPS (40 mg/kg per day) was administered by oral gavage to the GPS group, while the vehicle group received an equivalent volume of the vehicle solution. At the end of the treatment, blood and aortic tissues were collected for assessments of atherosclerosis, lipid profiles, oxidative stress, and molecular expressions related to NLRP3 inflammasome activation, ROS production, and apoptosis. Additionally, in vitro experiments on human aortic endothelial cells treated with oxidized low-density lipoprotein (ox-LDL) were conducted to evaluate the effects of GPS on NLRP3 inflammasome activation, pyroptosis, apoptosis, and ROS production, specifically examining the role of the sirtuin 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. SIRT1 and Nrf2 inhibitors were used to confirm the pathway's role. RESULTS: GPS treatment significantly reduced atherosclerotic lesions in the en face aorta (P<0.01), as well as in the thoracic and abdominal aortic regions, and markedly decreased sinus lesions within the aortic root (P<0.05 or P<0.01). Additionally, GPS reduced oxidative stress markers and proinflammatory cytokines, including interleukin (IL)-1 β and IL-18, in lesion areas (P<0.05, P<0.01). In vitro, GPS inhibited ox-LDL-induced NLRP3 activation, as evidenced by reduced NLRP3 (P<0.01), apoptosis-associated speck-like protein containing a CARD, cleaved-caspase-1, and cleaved-gasdermin D expressions (all P<0.01). GPS also decreased ROS production, apoptosis, and pyroptosis, with the beneficial effects being significantly reversed by SIRT1 or Nrf2 inhibitors. CONCLUSION GPS exerts an antiatherogenic effect by inhibiting ROS-dependent NLRP3 inflammasome activation via the SIRT1/Nrf2 pathway.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Reactive Oxygen Species/metabolism* ; Iridoid Glucosides/therapeutic use* ; NF-E2-Related Factor 2/metabolism* ; Animals ; Atherosclerosis/metabolism* ; Inflammasomes/drug effects* ; Male ; Sirtuin 1/metabolism* ; Signal Transduction/drug effects* ; Humans ; Endothelial Cells/pathology* ; Mice ; Oxidative Stress/drug effects* ; Apoptosis/drug effects* ; Lipoproteins, LDL ; Mice, Inbred C57BL

OBJECTIVE: To investigate the effect and mechanism of Shuangshi Tonglin Capsules (SSTL) in the treatment of prostate fibrosis (PF). METHODS: Human prostate stromal cells (WPMY-1) were used for in vitro experiments to establish PF cell models induced with estradiol (E₂). The cell proliferation, migration and clonogenic capacity were determined by cell counting kit-8, scratch assay, and crystal violet staining, respectively. Sprague-Dawley rats were used for in vivo experiments. The changes in histomorphology and organ index of rat prostate by SSTL were determined. Pathologic changes and collagen deposition changes in rat prostate were observed by haematoxylin and eosin (HE) and Masson staining. Enzyme-linked immunosorbent assay kits were used to determine changes in rat PF markers fibroblast growth factor-23 (FGF-23), E₂ and prostate specific antigen (PSA). Mechanistically, changes in oxidative stress indicators by SSTL were determined in WPMY-1 cells and PF rats. Then the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) and transforming growth factor-β1 (TGF-β1)/Smad pathway-related proteins as well as Nrf2 and TGF-β1 mRNA were further detected by Western blot or quantitative real-time polymerase chain reaction both in vivo and in vitro. RESULTS: In the efficacy study, SSTL significantly reduced the proliferation, migration, and clonogenic ability of cells, improved the morphology of the glandular tissue, significantly reduced the prostate index, reduced glandular fibrous tissue and collagen deposition, and resulted in a significant decrease in the levels of FGF-23, E₂ and PSA (P<0.01 or P<0.05). In the mechanistic study, SSTL ameliorated oxidative stress by significantly increasing superoxide dismutase and glutathione peroxidase levels and decreasing malondialdehyde level in WPMY-1 cells and rats (P<0.01 or P<0.05). SSTL significantly elevated the expressions of Nrf2, HO-1, NAD(P)H quinone oxidoreductase 1 (NQO-1), and Smad7 proteins in both cells and rats, and significantly decreased the expressions of TGF-β1, collagen I, α-smooth muscle actin and Smad4 proteins (P<0.01 or P<0.05). SSTL also elevated the content of Nrf2 mRNA and decreased the content of TGF-β1 mRNA in cells and rats (P<0.01 or P<0.05). The Nrf2 inhibitor ML385 was added in in vitro experiments to further validate the pathway relevance. CONCLUSION SSTL was effective in improving PF in vivo and in vitro, and its mechanism of action may function through the Nrf2/TGF-β1 signaling pathway.
Male ; NF-E2-Related Factor 2/metabolism* ; Animals ; Drugs, Chinese Herbal/therapeutic use* ; Signal Transduction/drug effects* ; Transforming Growth Factor beta1/metabolism* ; Rats, Sprague-Dawley ; Humans ; Fibrosis ; Prostate/drug effects* ; Cell Proliferation/drug effects* ; Capsules ; Cell Movement/drug effects* ; Oxidative Stress/drug effects* ; Rats

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Objective:To investigate the clinical efficacy of reconstruction with the hallux tissue flap for the fingertip defects of thumb and fingers based on the concept and technique of full reconstruction.Methods:From September 2022 to February 2023, the patients with thumb and fingertip defects who were reconstructed using the concept and technology of full reconstruction in Xuzhou Renci Hospital were respective analysised. Based on the degree of defect in the nail bed, bone, and soft tissue of the hand, a hallux osteo-onychocutaneous flap or hallux nail flap was designed and harvested from the same side of the toe, and free transplantation was performed to reconstruct the damaged fingertip. The wounds in the donor site that could not be sutured primarily were treated with dressing change. The surgical complications, the appearance of the reconstructed finger and donor site, Semmes-Weinstein monofilament (SWM) examination, 2-point discrimination (2PD) measurement, and patient satisfaction were regularly recorded. According to the functional evaluation criteria for thumb and finger reconstruction issued by the Hand Surgery of the Chinese Medical Association, the function of the reconstructed fingers was evaluated as excellent (13-15 points), good (9-12 points), fair (5-8 points), and poor (≤4 points). The patients were investigated whether they were satisfied with the outcomes.Results:A total of 8 patients (9 fingers) including 5 males and 3 females were enrolled. The average age was 32.4 years (range, 22-46 years). There were 1 thumb, 2 index fingers, 5 middle fingers, and 1 ring finger. 7 cases (8 fingers) were repaired with the hallux osteo-onychocutaneous flap, and 1 case (1 finger) was repaired with the hallux nail flap. All the reconstructed fingers survived uneventfully, and the recipient site healed primarily, and the donor site healed after dressing change, without infection and other complications. All the 8 patients (9 fingers) were followed up for 3-7 months. The nail plate of the donor site naturally grew and recovered nearly normal. Depression formation was observed at part of the deck junction of the recipient site, and scars were left in the pulp and fibular side of the hallux. At the final follow-up, the reconstructed fingers recovered protective sensation and tactile sense, and the 2PD of the reconstructed fingers was 9 mm and 10 mm in two cases. The SWM score was 3.60-4.31, mean 3.96. The results were the monofilament specifications and indicating the protective sensation was diminished. Functional evaluation of reconstructed fingers: 9 fingers in 8 cases scored 13-14 points, all reaching an excellent level. All patients were satisfied with the surgical results.Conclusion:Based on the concept and technology of full reconstruction, the fingertip defects of the thumb and finger can recover close to normal with the hallux tissue flap in the short-term, while ensuring the overall shape and function of the hallux donor area, achieving a balance between the donor and recipient areas, and achieving satisfactory clinical results.

Objective:To investigate the clinical efficacy of reconstruction with the hallux tissue flap for the fingertip defects of thumb and fingers based on the concept and technique of full reconstruction.Methods:From September 2022 to February 2023, the patients with thumb and fingertip defects who were reconstructed using the concept and technology of full reconstruction in Xuzhou Renci Hospital were respective analysised. Based on the degree of defect in the nail bed, bone, and soft tissue of the hand, a hallux osteo-onychocutaneous flap or hallux nail flap was designed and harvested from the same side of the toe, and free transplantation was performed to reconstruct the damaged fingertip. The wounds in the donor site that could not be sutured primarily were treated with dressing change. The surgical complications, the appearance of the reconstructed finger and donor site, Semmes-Weinstein monofilament (SWM) examination, 2-point discrimination (2PD) measurement, and patient satisfaction were regularly recorded. According to the functional evaluation criteria for thumb and finger reconstruction issued by the Hand Surgery of the Chinese Medical Association, the function of the reconstructed fingers was evaluated as excellent (13-15 points), good (9-12 points), fair (5-8 points), and poor (≤4 points). The patients were investigated whether they were satisfied with the outcomes.Results:A total of 8 patients (9 fingers) including 5 males and 3 females were enrolled. The average age was 32.4 years (range, 22-46 years). There were 1 thumb, 2 index fingers, 5 middle fingers, and 1 ring finger. 7 cases (8 fingers) were repaired with the hallux osteo-onychocutaneous flap, and 1 case (1 finger) was repaired with the hallux nail flap. All the reconstructed fingers survived uneventfully, and the recipient site healed primarily, and the donor site healed after dressing change, without infection and other complications. All the 8 patients (9 fingers) were followed up for 3-7 months. The nail plate of the donor site naturally grew and recovered nearly normal. Depression formation was observed at part of the deck junction of the recipient site, and scars were left in the pulp and fibular side of the hallux. At the final follow-up, the reconstructed fingers recovered protective sensation and tactile sense, and the 2PD of the reconstructed fingers was 9 mm and 10 mm in two cases. The SWM score was 3.60-4.31, mean 3.96. The results were the monofilament specifications and indicating the protective sensation was diminished. Functional evaluation of reconstructed fingers: 9 fingers in 8 cases scored 13-14 points, all reaching an excellent level. All patients were satisfied with the surgical results.Conclusion:Based on the concept and technology of full reconstruction, the fingertip defects of the thumb and finger can recover close to normal with the hallux tissue flap in the short-term, while ensuring the overall shape and function of the hallux donor area, achieving a balance between the donor and recipient areas, and achieving satisfactory clinical results.

Although there are continuous progresses in economy and society, the accelerated aging process has brought widespread impacts on various aspects of society and economy in China, especially on the supply of the working-age population. Effectively addressing labor force aging has become an urgent challenge for China's economic and social development. North American countries, particularly the United States and Canada, are also facing severe aging population issues, and have entered an aging society earlier than China. These countries have alleviated labor supply shortages through proactive immigration policies, while implementing flexible retirement, reemployment of elderly individuals, and vocational training policies to effectively encourage elderly workers to remain in their jobs. Additionally, the occupational health programs of large enterprises in North America have yielded positive returns on their health investments. Building upon an overview of the current situation and corresponding measures in response to the aging working-age population in North America, this paper presented constructive recommendations to address the aging population issue in China.

AIM To investigate the variation rules of main secondary metabolites in Hedysari Radix before and after rubbing strip.METHODS UPLC-MS/MS was adopted in the content determination of formononetin,ononin,calycosin,calycosin-7-glucoside,medicarpin,genistein,luteolin,liquiritigenin,isoliquiritigenin,vanillic acid,ferulic acid,γ-aminobutyric acid,adenosine and betaine,after which cluster analysis,principal component analysis and orthogonal partial least squares discriminant analysis were used for chemical pattern recognition to explore differential components.RESULTS After rubbing strip,formononetin,calycosin,liquiritigenin and γ-aminobutynic acid demonstrated increased contents,along with decreased contents of ononin,calycosin-7-glucoside and vanillic acid.The samples with and without rubbing strip were clustered into two types,calycosin-7-glucoside,formononetin,γ-aminobutynic acid,vanillic acid,calycosin-7-glucoside and formononetin were differential components.CONCLUSION This experiment clarifies the differences of chemical constituents in Hedysari Radix before and after rubbing strip,which can provide a reference for the research on rubbing strip mechanism of other medicinal materials.