Objective:To investigate the role of Gasdermin E (GSDME) -mediated keratinocyte pyroptosis induced by Cutibacterium acnes ( C.acnes) in the pathogenesis of acne. Methods:The human immortalized keratinocyte HaCaT cells were stimulated with heat-inactived C.acnes for 15 minutes to 24 hours, and Western blot analysis was performed to determine the expression of cleaved GSDME (GSDME-NT) in HaCaT cells at different time points. Skin tissue samples were collected from 5 acne patients and 4 healthy controls, who visited the Hospital for Skin Diseases, Chinese Academy of Medical Sciences from January 2 to December 1, 2024; additionally, 3 samples of acne cyst contents and 3 samples of normal follicle contents were collected. Immunohistochemical study and Western blot analysis were conducted to determine GSDME-NT expression in the epidermis. Enzyme-linked immunosorbent assay (ELISA) was performed to detect levels of interleukin (IL) -1β and tumor necrosis factor (TNF) -α in acne cyst or normal follicle contents. GSDME-knockdown HaCaT cells were constructed by transfection with lentivirus carrying GSDME-shRNA, and HaCaT cells transfected with lentivirus carrying the nonsense sequence control (NC) served as controls; ELISA was performed to detect the levels of IL-1β and TNF-α in GSDME-knockdown HaCaT cells after C. acnes stimulation ( C. acnes + GSDME knockdown group) , as well as in the phosphate-buffered saline (PBS) + NC group, C. acnes + NC group, and PBS + GSDME knockdown group. Western blot analysis was conducted to determine the GSDME-NT expression in HaCaT cells pretreated with or without retinol after C. acnes stimulation. Results:The cleavage of GSDME in HaCaT cells began at 1 hour after in vitro C. acnes stimulation, and GSDME-NT could be detected at this time. Compared with the control epidermis, the proportion of GSDME-NT-positive HaCaT cells (9.34% ± 2.92% vs. 3.05% ± 1.14%, t = -3.47, P = 0.026) and GSDME-NT protein expression levels ( t = -3.51, P = 0.025) significantly increased in the lesional epidermis of acne patients. The levels of IL-1β and TNF-α were significantly higher in the acne cyst contents than in the normal follicle contents (IL-1β: 1 337.24 [1 182.32, 2 230.61] pg/ml vs. 0.00 [0.00, 108.21] pg/ml, Z = 1.99, P = 0.046; TNF-α: 811.31 [438.26, 817.73] pg/ml vs. 46.67 [12.41, 53.21] pg/ml, Z = 1.96, P = 0.049) . ELISA showed that the levels of IL-1β and TNF-α were significantly higher in the C. acnes + NC group (12.12 ± 3.07 pg/ml, 26.06 ± 1.57 pg/ml, respectively) than in the PBS + NC group (3.73 ± 2.24 pg/ml, 10.14 ± 0.79 pg/ml, P = 0.003, < 0.001, respectively) ; compared with the C. acnes + NC group, the levels of IL-1β and TNF-α significantly decreased in the C. acnes + GSDME knockdown group (3.38 ± 0.93 pg/ml, 12.67 ± 2.10 pg/ml, P = 0.003, < 0.001, respectively) . The GSDME-NT expression was significantly lower in the retinol + C. acnes group than in the C. acnes group ( P = 0.029) . Conclusion:C. acnes may induce GSDME-mediated pyroptosis in keratinocytes, thereby promoting the release of inflammatory factors and aggravating the inflammatory response in acne, while retinol may be able to inhibit this process.

Objective To explore the clinical efficacy of wrist arthroscopy assisted closed reduction with external fixation in the treatment of intra-articular comminuted fractures of the distal radius(type C3).Methods A retrospective analysis was conducted on 98 patients with type C3 intra-articular comminuted fractures of the distal radius admitted to our hospital from March 2022 to February 2023.Among them,48 patients underwent wrist arthroscopy assisted closed reduction with external fixation with a bracket(arthroscopy group),and another 50 patients underwent open reduction with steel plate internal fixation surgery(control group).The two groups were compared in terms of operation time,intraoperative bleeding volume,incision length,fracture union time,range of motion(ROM)of joint,Visual Analogue Scale(VAS),and Gartland-Werley wrist scores,as well as radiographic parameters(palmar tilt,ulnar inclination,and radial height)evaluated at various follow-up intervals.Results The arthroscopy group had an operation time of(55.3±10.5)min,which was significantly shorter than that in the control group[(83.4±14.6)min;t=-10.979,P=0.000].The intraoperative bleeding volume in the arthroscopy group was(42.3±8.6)ml,which was less than that in the control group[(71.4±10.5)ml;t=-14.953,P=0.000].The incision length of the arthroscopy group was(1.3±0.3)cm,which was shorter than that of the control group[(5.1±1.5)cm;t=-18.550,P=0.000].The arthroscopy group had a fracture healing time of(10.7±1.4)weeks,which was shorter than that in the control group[(12.2±1.6)weeks;t=-4.855,P=0.000].The palmar flexion ROM in the arthroscopy group was 68.8°±8.3°,which was significantly higher than that in the control group(61.5°±9.4°;t=4.002,P=0.000).The dorsiflexion ROM in the arthroscopy group was 63.9°±7.5°,which was significantly higher than that in the comtrol group(59.2°±8.3°;t=2.931,P=0.004).The pronation ROM in the arthroscopy group was 67.4°±10.3°,which was significantly higher than that in the control group(62.1°±9.9°;t=2.604,P=0.011).The supination ROM in the arthroscopy group was 70.5°±7.4°,which was significantly higher than that in the control group(64.4°±8.6°;t=3.777,P=0.000).The VAS score of the arthroscopy group was(1.3±0.6)points,which was significantly lower than that in the control group[(1.7±0.5)points;t=-3.941,P=0.000].After 6 months,the Gartland-Werley wrist scores of the arthroscopy group was significantly higher than that of the control group(Z=-2.614,P=0.009).The wrist joint imaging showed significantly higher radial height,palmar inclination angle,and ulnar deviation angle in the arthroscopy group than the control group(all P=0.000),while there were no significant differences in palmar inclination angle and ulnar deviation angle at different time points within each group(P＞0.05).Except for significant differences in radial height at 3 d,1 month,and 6 months after surgery(P=0.015,P=0.035),there were no significant differences between any other time points(P＞0.05).The interaction between time and group was not significant for palm inclination angle,ulnar deviation angle,and radial height(P＞0.05).Conclusion Wrist arthroscopy assisted closed reduction with external fixation for intra-articular comminuted fractures of distal radius has advantages of short operation time,less intraoperative blood loss,and good recovery of wrist joint functions.

Dental trauma is one of the relatively common emergencies in clinical dental practice, with a high incidence rate, and the maxillary central incisors are the most frequently affected. This article reports a case of a 17-year-old female patient who suffered traumatic complete avulsion of teeth 11 and 21, with tooth 21 lost after avulsion. The prognosis for replantation was poor due to the absence of the buccal alveolar bone wall of tooth 11. Therefore, tooth 11 was treated with extracorporeal root canal therapy and then replanted into the alveolar socket of tooth 21, which had better conditions, followed by elastic splint fixation. After 20 months of follow-up observation, the affected tooth maintained a stable functional position, with no periapical inflammation or ankylosis observed. Subsequently, delayed implant restoration at the site of tooth 11 was performed, ultimately achieving a favorable treatment outcome. This case may provide new insights and references for future clinical practices in tooth replantation.
Humans ; Female ; Tooth Replantation/methods* ; Incisor/injuries* ; Adolescent ; Tooth Avulsion/therapy* ; Maxilla ; Root Canal Therapy

Tertiary lymphoid structures (TLSs), as a crucial component of the tumor micro-environment, have attracted significant attention in the field of tumor research in recent years. TLSs are composed of multiple immune cells and formed under the stimulation of chronic inflammation, with their maturation process divided into different stages. They exert anti-tumor effects by mimic-king the functions of secondary lymphoid organs and generating adaptive immune responses. In terms of the prognosis of gastric cancer, the cell composition, spatial distribution of TLSs, and their combination with other indicators are all helpful in predicting the prognosis of patients. Meanwhile, the TLSs scoring system is expected to become an index for evaluating the efficacy of immuno-therapy. Treatment strategies for inducing TLSs formation have achieved certain results in animal models, but potential treatment risks require attention. The authors elaborate on formation and maturation process of TLSs, anti-tumor mechanism, value in prognostic assessment of gastric cancer and multiple tumors, prediction of immunotherapy, as well as treatment strategies for inducing the formation of TLSs.

Objective:To investigate the role of Gasdermin E (GSDME) -mediated keratinocyte pyroptosis induced by Cutibacterium acnes ( C.acnes) in the pathogenesis of acne. Methods:The human immortalized keratinocyte HaCaT cells were stimulated with heat-inactived C.acnes for 15 minutes to 24 hours, and Western blot analysis was performed to determine the expression of cleaved GSDME (GSDME-NT) in HaCaT cells at different time points. Skin tissue samples were collected from 5 acne patients and 4 healthy controls, who visited the Hospital for Skin Diseases, Chinese Academy of Medical Sciences from January 2 to December 1, 2024; additionally, 3 samples of acne cyst contents and 3 samples of normal follicle contents were collected. Immunohistochemical study and Western blot analysis were conducted to determine GSDME-NT expression in the epidermis. Enzyme-linked immunosorbent assay (ELISA) was performed to detect levels of interleukin (IL) -1β and tumor necrosis factor (TNF) -α in acne cyst or normal follicle contents. GSDME-knockdown HaCaT cells were constructed by transfection with lentivirus carrying GSDME-shRNA, and HaCaT cells transfected with lentivirus carrying the nonsense sequence control (NC) served as controls; ELISA was performed to detect the levels of IL-1β and TNF-α in GSDME-knockdown HaCaT cells after C. acnes stimulation ( C. acnes + GSDME knockdown group) , as well as in the phosphate-buffered saline (PBS) + NC group, C. acnes + NC group, and PBS + GSDME knockdown group. Western blot analysis was conducted to determine the GSDME-NT expression in HaCaT cells pretreated with or without retinol after C. acnes stimulation. Results:The cleavage of GSDME in HaCaT cells began at 1 hour after in vitro C. acnes stimulation, and GSDME-NT could be detected at this time. Compared with the control epidermis, the proportion of GSDME-NT-positive HaCaT cells (9.34% ± 2.92% vs. 3.05% ± 1.14%, t = -3.47, P = 0.026) and GSDME-NT protein expression levels ( t = -3.51, P = 0.025) significantly increased in the lesional epidermis of acne patients. The levels of IL-1β and TNF-α were significantly higher in the acne cyst contents than in the normal follicle contents (IL-1β: 1 337.24 [1 182.32, 2 230.61] pg/ml vs. 0.00 [0.00, 108.21] pg/ml, Z = 1.99, P = 0.046; TNF-α: 811.31 [438.26, 817.73] pg/ml vs. 46.67 [12.41, 53.21] pg/ml, Z = 1.96, P = 0.049) . ELISA showed that the levels of IL-1β and TNF-α were significantly higher in the C. acnes + NC group (12.12 ± 3.07 pg/ml, 26.06 ± 1.57 pg/ml, respectively) than in the PBS + NC group (3.73 ± 2.24 pg/ml, 10.14 ± 0.79 pg/ml, P = 0.003, < 0.001, respectively) ; compared with the C. acnes + NC group, the levels of IL-1β and TNF-α significantly decreased in the C. acnes + GSDME knockdown group (3.38 ± 0.93 pg/ml, 12.67 ± 2.10 pg/ml, P = 0.003, < 0.001, respectively) . The GSDME-NT expression was significantly lower in the retinol + C. acnes group than in the C. acnes group ( P = 0.029) . Conclusion:C. acnes may induce GSDME-mediated pyroptosis in keratinocytes, thereby promoting the release of inflammatory factors and aggravating the inflammatory response in acne, while retinol may be able to inhibit this process.

Tertiary lymphoid structures (TLSs), as a crucial component of the tumor micro-environment, have attracted significant attention in the field of tumor research in recent years. TLSs are composed of multiple immune cells and formed under the stimulation of chronic inflammation, with their maturation process divided into different stages. They exert anti-tumor effects by mimic-king the functions of secondary lymphoid organs and generating adaptive immune responses. In terms of the prognosis of gastric cancer, the cell composition, spatial distribution of TLSs, and their combination with other indicators are all helpful in predicting the prognosis of patients. Meanwhile, the TLSs scoring system is expected to become an index for evaluating the efficacy of immuno-therapy. Treatment strategies for inducing TLSs formation have achieved certain results in animal models, but potential treatment risks require attention. The authors elaborate on formation and maturation process of TLSs, anti-tumor mechanism, value in prognostic assessment of gastric cancer and multiple tumors, prediction of immunotherapy, as well as treatment strategies for inducing the formation of TLSs.

Objective To explore the clinical efficacy of wrist arthroscopy assisted closed reduction with external fixation in the treatment of intra-articular comminuted fractures of the distal radius(type C3).Methods A retrospective analysis was conducted on 98 patients with type C3 intra-articular comminuted fractures of the distal radius admitted to our hospital from March 2022 to February 2023.Among them,48 patients underwent wrist arthroscopy assisted closed reduction with external fixation with a bracket(arthroscopy group),and another 50 patients underwent open reduction with steel plate internal fixation surgery(control group).The two groups were compared in terms of operation time,intraoperative bleeding volume,incision length,fracture union time,range of motion(ROM)of joint,Visual Analogue Scale(VAS),and Gartland-Werley wrist scores,as well as radiographic parameters(palmar tilt,ulnar inclination,and radial height)evaluated at various follow-up intervals.Results The arthroscopy group had an operation time of(55.3±10.5)min,which was significantly shorter than that in the control group[(83.4±14.6)min;t=-10.979,P=0.000].The intraoperative bleeding volume in the arthroscopy group was(42.3±8.6)ml,which was less than that in the control group[(71.4±10.5)ml;t=-14.953,P=0.000].The incision length of the arthroscopy group was(1.3±0.3)cm,which was shorter than that of the control group[(5.1±1.5)cm;t=-18.550,P=0.000].The arthroscopy group had a fracture healing time of(10.7±1.4)weeks,which was shorter than that in the control group[(12.2±1.6)weeks;t=-4.855,P=0.000].The palmar flexion ROM in the arthroscopy group was 68.8°±8.3°,which was significantly higher than that in the control group(61.5°±9.4°;t=4.002,P=0.000).The dorsiflexion ROM in the arthroscopy group was 63.9°±7.5°,which was significantly higher than that in the comtrol group(59.2°±8.3°;t=2.931,P=0.004).The pronation ROM in the arthroscopy group was 67.4°±10.3°,which was significantly higher than that in the control group(62.1°±9.9°;t=2.604,P=0.011).The supination ROM in the arthroscopy group was 70.5°±7.4°,which was significantly higher than that in the control group(64.4°±8.6°;t=3.777,P=0.000).The VAS score of the arthroscopy group was(1.3±0.6)points,which was significantly lower than that in the control group[(1.7±0.5)points;t=-3.941,P=0.000].After 6 months,the Gartland-Werley wrist scores of the arthroscopy group was significantly higher than that of the control group(Z=-2.614,P=0.009).The wrist joint imaging showed significantly higher radial height,palmar inclination angle,and ulnar deviation angle in the arthroscopy group than the control group(all P=0.000),while there were no significant differences in palmar inclination angle and ulnar deviation angle at different time points within each group(P＞0.05).Except for significant differences in radial height at 3 d,1 month,and 6 months after surgery(P=0.015,P=0.035),there were no significant differences between any other time points(P＞0.05).The interaction between time and group was not significant for palm inclination angle,ulnar deviation angle,and radial height(P＞0.05).Conclusion Wrist arthroscopy assisted closed reduction with external fixation for intra-articular comminuted fractures of distal radius has advantages of short operation time,less intraoperative blood loss,and good recovery of wrist joint functions.

Objective This project aimed to study the Miao medicine helleborus thibetanus franchon,including investigating its anti-inflammatory activity in collagen-induced arthritis CIA rats and its mechanism of VEGF/VEGFR2/P38 MAPK pathway regulation.Methods Sixty female Wistar rats were randomly divided into six groups:normal;model;positive drug;and low,medium,high dose groups,with 10 rats in each group.Bovine type Ⅱ collagen solution was injected into the tail of rats to construct the rheumatoid arthritis model,and the positive drug group was given MTX2.0 mg/(kg·d)by gavage once every other day.The three groups of helleborus thibetanus franchon low,medium,and high dose were gavaged with helleborus thibetanus franchon ethanol extract at 0.25,0.5 and 1 g/(kg·d)once a day.The normal and model groups were given an equivalent volume of NaCl solution,with continuous administration lasting for 28 days.During treatment,the general condition of the rats was observed,body weight changes recorded,and foot thickness measured.After treatment and euthanasia,the rats'hind limbs were removed for Micro-CT to detect bone destruction;hematoxylin and eosin staining for pathological investigattion of the synovial membrane;immunohistochemistry to observe neovascularization in the synovium;quantitative reverse-transcription PCR to detect mRNA levels of VEGF-A,VEGFR2,TNF-α in the synovial tissue;and Western Blot to detect the expression of VEGF,VEGFR2,p-P38,p-AKT.The analyses were used to explore the potential mechanisms of action of the Miao medicine helleborus thibetanus franchon in treating rheumatoid arthritis.Results Compared with the normal group,the model group showed significant weight loss(P＜0.01),increased foot swelling(P＜0.01),visible proliferative synovial tissue with inflammatory cell infiltration,erosive lesions on bone surfaces,increased neovascularization in the synovium,and significant bone destruction in Micro-CT,with reduced bone percentage,trabecular thickness,and bone density.The levels of VEGF-A,VEGFR2,TNF-α mRNA and VEGF-A,VEGFR2,p-P38,p-AKT proteins were significantly elevated(P＜0.01).Compared with the model group,the helleborus thibetanus franchon ethanol extract-treated groups showed improvements in these conditions in a dose-dependent manner,with the high-dose group receiving the best effect.There was a significant increase in the rats'body weight(P＜0.05);reduction in foot swelling(P＜0.05);amelioration of synovial and erosive bone lesions;reduction in neovascularization in the synovium;and significantly lower levels of VEGF-A,VEGFR2,and TNF-α mRNA,and VEGF-A,VEGFR2,p-P38,and p-AKT protein(P＜0.01).Conclusions The Miao medicine plant helleborus thibetanus franchon may alleviate joint inflammatory damage in CIA rats by modulating the VEGF/VEGFR2 signaling pathway,thereby exerting therapeutic effects on rheumatoid arthritis.

Background::Accurately and efficiently extracting microbial genomic sequences from complex metagenomic data is crucial for advancing our understanding in fields such as clinical diagnostics, environmental microbiology, and biodiversity. As sequencing technologies evolve, this task becomes increasingly challenging due to the intricate nature of microbial communities and the vast amount of data generated. Especially in intensive care units (ICUs), infections caused by antibiotic-resistant bacteria are increasingly prevalent among critically ill patients, significantly impacting the effectiveness of treatments and patient prognoses. Therefore, obtaining timely and accurate information about infectious pathogens is of paramount importance for the treatment of patients with severe infections, which enables precisely targeted anti-infection therapies, and a tool that can extract microbial genomic sequences from metagenomic dataset would be of help.Methods::We developed MetaGeneMiner to help with retrieving specific microbial genomic sequences from metagenomes using a k-mer-based approach. It facilitates the rapid and accurate identification and analysis of pathogens. The tool is designed to be user-friendly and efficient on standard personal computers, allowing its use across a wide variety of settings. We validated MetaGeneMiner using eight metagenomic samples from ICU patients, which demonstrated its efficiency and accuracy.Results::The software extensively retrieved coding sequences of pathogens Acinetobacter baumannii and herpes simplex virus type 1 and detected a variety of resistance genes. All documentation and source codes for MetaGeneMiner are freely available at https://gitee.com/sculab/MetaGeneMiner. Conclusions::It is foreseeable that MetaGeneMiner possesses the potential for applications across multiple domains, including clinical diagnostics, environmental microbiology, gut microbiome research, as well as biodiversity and conservation biology. Particularly in ICU settings, MetaGeneMiner introduces a novel, rapid, and precise method for diagnosing and treating infections in critically ill patients. This tool is capable of efficiently identifying infectious pathogens, guiding personalized and precise treatment strategies, and monitoring the development of antibiotic resistance, significantly impacting the diagnosis and treatment of severe infections.

The biosynthesis and maturation of proteins are primarily regulated by the endoplasmic reticulum in its physiological state. Thus, the disruption of physiological homeostasis initiates the buildup of unfolded and misfolded proteins in the endoplasmic reticulum, resulting in endoplasmic reticulum stress (ERS) and unfolded protein response (UPR). One of the important pathways by which UPR maintains intracellular homeostasis under ERS is activating protein kinase R-like endoplasmic reticulum kinase (PERK). The activation of the PERK pathway stimulates eukaryotic translation initiation factor 2 subunit-α (eIF2α) phosphorylation and the selective translation of active transcription factor 4 (ATF4), and PERK induces cell apoptosis by directly binding to the promoter of pro-apoptotic transcription factor C/EBP homologous protein (CHOP). This signaling pathway is also one of the important mechanisms by which UPR participates in the regulation of hematological malignancies and immune cells in a tumor microenvironment. This article provides an overview of advancements in research into the PERK-eIF2α-ATF4-CHOP signaling pathway in hematological malignancies and the potential therapeutic benefits of targeting this signaling pathway.