Microglial pyroptosis and neuroinflammation have been implicated in the pathogenesis of sepsis-associated encephalopathy (SAE). OGT-mediated O-GlcNAcylation is involved in neurodevelopment and injury. However, its regulatory function in microglial pyroptosis and involvement in SAE remains unclear. In this study, we demonstrated that OGT deficiency augmented microglial pyroptosis and exacerbated secondary neuronal injury. Furthermore, OGT inhibition impaired cognitive function in healthy mice and accelerated the progression in SAE mice. Mechanistically, OGT-mediated O-GlcNAcylation of ATF2 at Ser44 inhibited its phosphorylation and nuclear translocation, thereby amplifying NLRP3 inflammasome activation and promoting inflammatory cytokine production in microglia in response to LPS/Nigericin stimulation. In conclusion, this study uncovers the critical role of OGT-mediated O-GlcNAcylation in modulating microglial activity through the regulation of ATF2 and thus protects against SAE progression.
Animals ; Microglia/metabolism* ; Pyroptosis/physiology* ; Mice ; Sepsis-Associated Encephalopathy/prevention & control* ; Activating Transcription Factor 2/metabolism* ; N-Acetylglucosaminyltransferases/genetics* ; Mice, Inbred C57BL ; Male ; Mice, Knockout

Objective:To evaluate the clinical effectiveness of the reconstruction of multiple digit-tip defects with transfer of polyfoliate perforator flaps of the fibular hallux.Methods:From January 2019 to June 2022, 15 patients had undergone reconstruction surgery for multiple digit-tip defects using polyfoliate perforator flaps of ipsilateral fibular hallux, with the first dorsal metatarsal artery as the pedicle, in the Department of Upper Limb Repair and Reconstruction Surgery, Guizhou Hospital of Beijing Jishuitan Hospital. The patients were 10 males and 5 females and aged 20 to 45 years old. Eight patients had the defects of thumbs and index fingers, 4 of thumbs and middle fingers, 2 of thumb, index and middle fingers and 1 of thumb, index and ring fingers. All the 15 digit injuries had nail bed defects to which reconstructive surgery were required. For the flaps of dorsal artery, flaps were 1.8 cm×2.0 cm-2.0 cm×3.1 cm in size and for those of plantar artery, the flaps sized 1.5 cm×2.0 cm-2.5 cm×3.0 cm. Donor site defects in the hallux were reconstructed with free superficial circumflex iliac perforator flaps. Postoperative follow-up lasted until 30th June 2023 and included visits to the outpatient clinic, WeChat and telephone reviews to assess the appearance, function and sensation recovery of the digits.Results:All the 15 flaps survived. During the 6 to 24 months (16 months in average) of postoperative follow-up, the appearance and texture of all flaps were found close to the healthy digits, with good nail growth and without deformity. TPD were found between 8.0 mm and 12.0 mm. The donor sites on the great toes that reconstructed with superficial circumflex iliac artery flaps were all survived well, and the incisions were satisfactorily healed without the functions of walking, running or jumping being significantly affected.Conclusion:The use of polyfoliate perforator flaps of fibular hallux for reconstruction of multiple digit-tip defects is an ideal surgical method due to the consistency of vascular anatomy, ease with flap harvest, similarity in the normal digital skin texture, and the capability to include a nail bed with the flap. A single donor from the hallux can simultaneously reconstruct two defects of digit-tip, making it an excellent treatment in the reconstruction of small-to medium-sized composite tissue defects in multiple digits.

Objective:To explore the clinical characteristics and experiences in diagnosis and treatment of severe hand injuries caused by chaff cutters.Methods:A retrospective analysis was conducted on 60 patients (193 digits) who had mangled hand injuries caused by chaff cutters and admitted to the Department of Upper Limb Repair and Reconstruction, Beijing Jishuitan Hospital Guizhou Hospital between January 2015 and June 2022. The patients were 39 males and 21 females, with 10 to 72 (mean 42.6) years old of age. The injuries involved 41 right hands and 19 left hands. The extent of hand injuries of soft tissue and bones varied from digit-tips to wrist. Among them, 5 digits were completely destroyed in 8 cases, 3 digits including thumb were destroyed in 12 cases, 4 digits including thumb were destroyed in 10 cases, 3 or more fingers without thumb were destroyed in 8 cases, simple hand destroyed in 8 cases, digits and palm destroyed in 8 cases, and total hand destroyed in 6 cases. The sizes of wound ranged from 1.8 cm×2.0 cm to 6.8 cm×15.6 cm. Based on the wound contamination and conditions of tissue damage, surgical treatment included debridement, stump trimming, in-situ replantation, transpositional replantation, venous bridging flap transfer and emergency or phased free second toe and free flap transfers. The flap sizes were 3.0 cm×5.0 cm-7.0 cm×16.0 cm. Both the reconstructed and flap donor sites were primarily closed in one stage. Postoperative follow-ups were conducted through regular visits of outpatient clinic or via WeChat interviews. The survival and functional recovery of flap and finger were observed.Results:Of the 60 patients, emergency orthotopic replantation of 112 digits were performed with survival of 96 digits; 16 digits transposition replantation were carried out with 12 survived; 5 digits received venous bridging flap transfer with 4 survived; all 5 Flow-through anteriolateral thigh perforator flaps (ALTPFs) were survived; all of 12 phase II digit reconstructions with free second toe transfer survived; and all 18 phase II free flap transfers survived [10 ALTPFs and 8 superficial circumflex iliac artery perforator flaps(SCIAPFs)]. Postoperative complications such as wound exudation and fever happened in 8 patients, and all were rectified after debridement and symptomatic anti-infection treatment. The follow-up ranged 6 to 18 months, with 12 months in average. Hand functions were assessed using the Michigan Hand Outcomes Questionnaire (MHQ), and the scores achieved at 20.3 to 72.8 points, with 42.6 points ± 16.6 points in average.Conclusion:Severe hand injuries caused by chaff cutters are severe and complicated. A thorough assessment of wound contamination and residual digits and tissues are required. Successful surgical outcomes can be achieved through emergency and elective surgery with multiple microsurgical techniques and multi-phased surgical reconstructions, although overall functional recovery of the injured hand is often not quite realistic.

Objective:To explore the occurrence of dental fear in children with dental pulp disease and its relationship with temperament type and social development level.Methods:This study was a cross-sectional study, using convenience sampling method to select 327 children with dental and pulp diseases who visited the outpatient department of the Department of Stomatology of Hunan Children′s Hospital from March 2022 to March 2023 as the study subjects. We used the Chinese version of the Children′s Fear Survey Schedule-Dental Subscale (CFSS-DS) to evaluate the dental fear of children; The temperament types of the children were evaluated using the Chinese Preschool Children Temperament Scale (CPTS); The social development level of the children was evaluated using the Children′s Social Development Scale; Multiple logistic stepwise regression analysis was used to evaluate the influencing factors of dental fear in children with dental pulp disease.Results:A total of 106 out of 327 children with dental pulp disease developed dental fear, with an incidence rate of 32.42%(106/327). There was a statistically significant difference in the incidence of dental fear among children with different temperament types ( P<0.05). Children with troubled temperament had the highest incidence of dental fear (37/47, 78.72%), while those with mild temperament had the lowest incidence (16/124, 12.90%). There was a statistically significant difference in the incidence of dental fear among children with different levels of social development ( P<0.05). Children with low levels of social development had the highest incidence of dental fear (34/42, 80.95%). Girls, children with unpleasant dental experiences, weak oral health awareness, symptoms of toothache, parents with high school education or below, and families with an average monthly income of less than 3 000 yuan had a higher incidence of dental fear than boys; The incidence of dental fear in children with no unpleasant dental treatment experience, good oral health awareness, no symptoms of toothache, parents with a high school education or above, and a family average monthly income of ≥3 000 yuan was relatively low (all P<0.05). Multivariate logistic stepwise regression analysis showed that having unpleasant dental experiences ( OR=2.751, 95% CI: 1.774-4.268), weak oral health awareness ( OR=2.465, 95% CI: 1.627-3.734), parents with high or lower education levels ( OR=2.366, 95% CI: 1.583-3.535), negative temperament types ( OR=2.573, 95% CI: 1.685-3.929), moderate social development ( OR=0.397, 95% CI: 0.261-0.603), and high-level social development ( OR=0.416, 95% CI: 0.276-0.627) were the risk factors of dental fear in children with dental pulp disease (all P<0.05). Conclusions:The incidence of dental fear in children with dental pulp disease is higher, which is related to their temperament type and social development level.

Oral bacteria directly affect the disease status of dental caries and periodontal diseases. The dynamic oral microbiota cooperates with the host to reflect the information and status of immunity and metabolism through two-way communication along the oral cavity and the systemic organs. The oral cavity is one of the most important interaction windows between the human body and the environment. The microenvironment at different sites in the oral cavity has different microbial compositions and is regulated by complex signaling, hosts, and external environmental factors. These processes may affect or reflect human health because certain health states seem to be related to the composition of oral bacteria, and the destruction of the microbial community is related to systemic diseases. In this review, we discussed emerging and exciting evidence of complex and important connections between the oral microbes and multiple human systemic diseases, and the possible contribution of the oral microorganisms to systemic diseases. This review aims to enhance the interest to oral microbes on the whole human body, and also improve clinician's understanding of the role of oral microbes in systemic diseases. Microbial research in dentistry potentially enhances our knowledge of the pathogenic mechanisms of oral diseases, and at the same time, continuous advances in this frontier field may lead to a tangible impact on human health.
Bacteria ; Dental Caries/microbiology* ; Humans ; Microbiota ; Mouth/microbiology* ; Mouth Diseases/microbiology* ; Periodontal Diseases/microbiology*

As an emerging cancer therapeutic target, non-apoptotic cell death such as ferroptosis, necroptosis and pyroptosis, etc., has revealed significant potential in cancer treatment for bypassing apoptosis to enhance the undermined therapeutic efficacy triggered by apoptosis resistance. A variety of anticancer drugs, synthesized compounds and natural products have been proven recently to induce non-apoptotic cell death and exhibit excellent anti-tumor effects. Moreover, the convergence of nanotechnology with functional materials and biomedicine science has provided tremendous opportunities to construct non-apoptotic cell death-based nanomedicine for innovative cancer therapy. Nanocarriers are not only employed in targeted delivery of non-apoptotic inducers, but also used as therapeutic components to induce non-apoptotic cell death to achieve efficient tumor treatment. This review first introduces the main characteristics, the mechanism and various pharmacological modulators of different non-apoptotic cell death forms, including ferroptosis, necroptosis, pyroptosis, autophagy, paraptosis, lysosomal-dependent cell death, and oncosis. Second, we comprehensively review the latest progresses of nanomedicine that induces various forms of non-apoptotic cell death and focus on the nanomedicine targeting different pathways and components. Furthermore, the combination therapies of non-apoptotic cell death with photothermal therapy, photodynamic therapy, immunotherapy and other modalities are summarized. Finally, the challenges and future perspectives in this regard are also discussed.

Objective:To compare the numerical rating scales (NRS) and Oswestry disability index (ODI) of denosumab in Chinese postmenopausal osteoporosis patients after 3 months, and analyze the early adverse reactions to provide reference for clinical diagnosis and treatment.Methods:Using a prospective study method, 260 patients with postmenopausal osteoporosis who were outpatients and inpatients in the Second Affiliated Hospital of Soochow University from September 2020 to October 2021 were selected, and general information, including age, height, weight, bone mineral density, history of fragility fractures, and use of anti-osteoporosis drugs. All subjects received denosumab 60 mg subcutaneously, and were given calcium and vitamin D at the same time. Pain was scored by NRS before treatment and 3 months after treatment, and functional improvement was assessed by ODI.Results:After 3 months of denosumab treatment in postmenopausal women with osteoporosis, among patients with different age groups, different degrees of osteoporosis, history of fragility fractures, and history of use of anti-osteoporosis drugs, NRS score and ODI score were lower than those before treatment, and the difference was statistically significant ( P<0.05). In addition, in patients with a history of fragility fractures (mainly vertebral fractures), the NRS scores and the ODI score decreased more significantly, and the difference was statistically significant ( P<0.05); the NRS score and ODI score decreased more significantly in patients with severe osteoporosis than in patients with osteoporosis, and the difference was statistically significant ( P<0.05); the BMD value of lumbar spine was negatively correlated with the reduction of NRS score before and after treatment ( P=0.042). In this study, 260 patients had musculoskeletal pain in 6 (2.3%), fatigue in 5 (1.9%), rash in 4 (1.5%), urinary tract infection in 2 (0.7%), and dizziness in 2 (0.7%), 2 case of fever (0.7%), 1 case of hypocalcemia (0.4%), a total of 22 cases of adverse reactions were reported, and the overall adverse reaction rate was 8.5%. Conclusion:Denosumab can improve pain symptoms and functional disability early in the clinical application of Chinese postmenopausal women with osteoporosis, and the incidence of adverse reactions is low. Especially for postmenopausal female osteoporosis patients with severe osteoporosis, low lumbar spine bone density, and a history of fragility fractures (mainly vertebral fractures), the application effect is more significant.

Objective:To summarize the experience of 15 cases of balloon endovascular occlusion assisted aortic replacement.Methods:15 patients who needed reoperation after aortic surgery underwent endovascular balloon occlusion assisted aortic replacement by DSA guidance in the hybrid OR. Main inclusion criteria: The target vessel to be blocked cannot be directly blocked. Based on the last CTA before the operation, the diameter of the target vessel was measured, and the appropriate diameter balloon and the appropriate diameter balloon and the amount of contrast agent were selected. The vascular approach was selected according to the CTA.During the operation, the balloon was filled and fixed well, the distal invasive blood pressure waveform showed advection, and the pressure close to hydrostatic pressure as the complete blocking standard.Results:All 15 cases of balloon endovascular occlusion assisted aortic surgery were successful. After the operation, 14 target vessels normally without damage, and there was no vascular complication. One case after surgical three-branch stent surgery underwent the second thoracoabdominal aortic replacement operation. After the stent was blocked by the balloon, the new tissue in the stent fell off, and the celiac trunk and superior mesenteric artery were embolized for reoperation.Conclusion:Balloon endovascular occlusion technology expands the indications of aortic surgery and simplifies the operation, that is a safe and effective occlusion method. Whether the target vessel is suitable for balloon occlusion should be judged before the operation to avoid related complications.

Objective To study the effect of storage duration on compressive mechanical properties of rabbit patellar, so as to provide references for in vitro ligament storage.Methods The compressive mechanical properties of rabbit patellar ligament storaged at -20 ℃ at different storage durations (in 36 d) were tested with the universal tensile test machine. The microscopic morphology of collagen fibers was observed under the scanning electron microscopy (SEM). The enthalpy and denaturation temperature of collagen fibers were measured with differential scanning calorimetry (DSC).Results With the increase of storage duration, the compressive stress of the patellar ligament at 40% strain increased from 19 kPa to 112 kPa and then decreased to 57 kPa. SEM observation showed that the cross-linking of collagen fibers was initially strengthened and then weakened. DSC results showed that the enthalpy increased from 59.47 J/g to 67.10 J/g and then decreased to 54.43 J/g. The denaturation temperature increased from 67.62 ℃ to 77.28 ℃ and then decreased to 64.10 ℃.Conclusions When rabbit patellar ligament is stored at -20 ℃, with the increase of storage duration, the compressive stress of rabbit patellar ligament at 40% strain increases at first and then decreases. This change may be due to the variation of cross-linking level of collagen fibers. The stronger the cross-linking of collagen fibers, the stronger the compressive mechanical properties will be.

Objective:To investigate the stability of α-synuclein (α-Syn) aggregates formed by incubation with blood plasma of patients with Parkinson's disease (PD).Methods:Peripheral blood samples were collected from 10 patients diagnosed as having PD in our hospital from June 2020 to December 2020 and 10 healthy control subjects (HC) at the same time period. The 1 mg recombinant human α-Syn was dissolved in 140 μL 0.01 mol/L phosphate buffer solution (PBS), and then, incubated with plasma from HC and PD patients and PBS at 37 ℃ for 7 d (HC group, PD group and PBS group). Preformed fiber (PFF) group was used for subsequent experiment with 10 μg PFF. After digestion with different concentrations of trypsin (concentration ratios of trypsin/α-Syn=1:80, 1:40, and 1:20) and protease K (PK, 1.0, 1.5, and 2.0 μg/mL), the differences of α-Syn levels before and after digestion were detected by Western blotting.Results:(1) Effect of trypsin on PFF digestion: PFF gradually decreased with the increase of trypsin doses; when trypsin/α-Syn ratio=1:20, α-Syn aggregates with molecular weight greater than 35 000 were almost completely digested, and its digestion was significantly different as compared with that in other concentration ratios ( P<0.05). (2) Effect of trypsin on digestion of α-Syn aggregates: at the relative molecular weight<25 000, when the concentration ratio of trypsin/α-Syn=1:20, as compared with HC and PD groups, the PBS group had significantly more obvious decrease ( P<0.05). At the relative molecular weight 35 000-40 000, the α-Syn levels in PBS, HC and PD groups were significantly decreased as compared with those before digestion at all concentration ratios; as compared with HC and PD groups, the PBS group had significantly more obvious decrease ( P<0.05). At molecular weight>40 000, α-Syn decreased significantly in PD group only when the concentration ratio of trypsin/α-Syn=1:20, and the degrees of digestion was PBS group>HC group>PD group, with significant differences among groups ( P<0.05). (3) Effect of PK on PFF digestion: when PK concentration was 1.0, 1.5 or 2.0 μg/mL, α-Syn was basically digested at relative molecular weight>35 000, and α-Syn monomer was reduced and small fragment appeared at relative molecular weight<25 000; as compared with negative controls (0 μg/mL PK), these changes in groups of PK concentration of 1.0, 1.5 or 2.0 μg/mL were significantly different ( P<0.05). (4) Effect of PK on digestion of α-Syn aggregates: at relative molecular weight<25 000, α-Syn in PBS group was digested into smaller fragments while α-Syn in HC and PD groups was not digested; significant differences was noted among groups at the same concentration ( P<0.05). At relative molecular weight of 35 000-40 000, with the increase of PK concentration, the amount of α-Syn dimer in PBS group decreased (increased digestibility), that in HC group increased, however, that in PD group did not change obviously; significant difference was noted at the same concentration among the three groups ( P<0.05). At relative molecular weight>40 000, with the increase of PK concentration, α-Syn in PBS, HC and PD groups decreased to a certain extent, and significant difference was noted among groups at the same concentration ( P<0.05). Conclusion:The stability of α-Syn aggregates formed by incubation with plasma from PD patients is higher than that formed by incubation with HC plasma and PBS.