Kupffer cells (KCs), as residents and sentinels of the liver, are involved in the formation of hepatic fibrosis (HF). However, the biological functions of circular RNAs (circRNAs) in KCs to HF have not been determined. In this study, the expression levels of circRNAs, microRNAs, and messenger RNAs (mRNAs) in KCs from a mouse model of HF mice were investigated using microarray and circRNA-Seq analyses. circDcbld2 was identified as a candidate circRNA in HF, as evidenced by its up-regulation in KCs. Silver staining and mass spectrometry showed that Wtap and Igf2bp2 bind to cirDcbld2. The suppression of circDcbld2 expression decreased the KC inflammatory response and oxidative stress and inhibited hepatic stellate cell (HSCs) activation, attenuating mouse liver fibrogenesis. Mechanistically, Wtap mediated the N ⁶-methyladenosine (m6A) methylation of circDcbld2, and Igf2bp2 recognized m6A-modified circDcbld2 and increased its stability. circDcbld2 contributes to the occurrence of HF by binding miR-144-3p/Et-1 to regulate the inflammatory response and oxidative stress. These findings indicate that circDcbld2 functions via the m6A/circDcbld2/miR-144-3p/Et-1 axis and may act as a potential biomarker for HF treatment.

Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.

OBJECTIVE: To compare the effectiveness of O-arm navigation and C-arm navigation for guiding percutaneous long sacroiliac screws in treatment of Denis type Ⅱ sacral fractures. METHODS: A retrospective study was conducted on clinical data of the 46 patients with Denis type Ⅱ sacral fractures between April 2021 and October 2022. Among them, 19 patients underwent O-arm navigation assisted percutaneous long sacroiliac screw fixation (O-arm navigation group), and 27 patients underwent C-arm navigation assisted percutaneous long sacroiliac screw fixation (C-arm navigation group). There was no significant difference in gender, age, causes of injuries, Tile classification of pelvic fractures, combined injury, the interval from injury to operation between the two groups ( P>0.05). The intraoperative preparation time, the placement time of each screw, the fluoroscopy time of each screw during placement, screw position accuracy, the quality of fracture reduction, and fracture healing time were recorded and compared, postoperative complications were observed. Pelvic function was evaluated by Majeed score at last follow-up. RESULTS: All operations were completed successfully, and all incisions healed by first intention. Compared to the C-arm navigation group, the O-arm navigation group had shorter intraoperative preparation time, placement time of each screw, and fluoroscopy time, with significant differences ( P<0.05). There was no significant difference in screw position accuracy and the quality of fracture reduction ( P>0.05). There was no nerve or vascular injury during screw placed in the two groups. All patients in both groups were followed up, with the follow-up time of 6-21 months (mean, 12.0 months). Imaging re-examination showed that both groups achieved bony healing, and there was no significant difference in fracture healing time between the two groups ( P>0.05). During follow-up, there was no postoperative complications, such as screw loosening and breaking or loss of fracture reduction. At last follow-up, there was no significant difference in pelvic function between the two groups ( P>0.05). CONCLUSION Compared with the C-arm navigation, the O-arm navigation assisted percutaneous long sacroiliac screws for the treatment of Denis typeⅡsacral fractures can significantly shorten the intraoperative preparation time, screw placement time, and fluoroscopy time, improve the accuracy of screw placement, and obtain clearer navigation images.
Humans ; Fracture Fixation, Internal/methods* ; Retrospective Studies ; Imaging, Three-Dimensional ; Bone Screws ; Surgery, Computer-Assisted ; Tomography, X-Ray Computed ; Spinal Fractures/surgery* ; Fractures, Bone/surgery* ; Pelvic Bones/injuries* ; Postoperative Complications ; Neck Injuries

Objective To elucidate the role of programmed cell death factor 4(PDCD4)in mitochondrial dysfunction caused by sepsis-related vascular endothelial damage.Methods Cultured human umbilical vein endothelial cells(HUVECs)and mouse vascular endothelial cells(C166 cells)were transfected with a small interfering RNA targeting PDCD4 followed by treatment with lipopolysaccharide(LPS)alone or in combination with carbonyl cyanide 3-chlorophenylhydrazone(FCCP).The proteomic changes in the cells after PDCD4 knockdown were analyzed using LC-MS/MS technique.The mRNA expressions of PDCD4 and the genes associated with cell inflammation and apoptosis were detected with RT-PCR,and the expressions of FIS1,DRP1 and OPA1 proteins key to mitochondrial fission and fusion were determined using Western blotting.JC-1 and MitoSOX fluorescent probes were used to observe the changes in mitochondrial membrane potential and mitochondrial reactive oxygen species levels under by a laser confocal microscope.Results LPS stimulation of the cells significantly increased the mRNA expressions of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and monocyte chemoattractant protein 1(MCP1)and enhanced the cellular expression of PDCD4(P<0.05).Proteomic analysis suggested a correlation between PDCD4 knockdown and changes in mitochondrial dynamics in the cells.LPS treatment significantly increased the expressions of mitochondrial fission proteins FIS1 and DRP1 and lowered the expression of the fusion protein OPA1 in the cells(P<0.05),causing also mitochondrial oxidative stress and reduction of the mitochondrial membrane potential(P<0.05).In HUVECs,treatment with FCCP significantly attenuated the protective effect of PDCD4 knockdown,which inhibited LPS-induced inflammation and oxidative stress and restored the balance between mitochondrial fission and fusion.Conclusion PDCD4 knockdown protects vascular endothelial cells against LPS-induced damages by repressing mitochondrial fission and oxidative stress,promoting mitochondrial fusion,and maintaining normal mitochondrial function.

Objective To elucidate the role of programmed cell death factor 4(PDCD4)in mitochondrial dysfunction caused by sepsis-related vascular endothelial damage.Methods Cultured human umbilical vein endothelial cells(HUVECs)and mouse vascular endothelial cells(C166 cells)were transfected with a small interfering RNA targeting PDCD4 followed by treatment with lipopolysaccharide(LPS)alone or in combination with carbonyl cyanide 3-chlorophenylhydrazone(FCCP).The proteomic changes in the cells after PDCD4 knockdown were analyzed using LC-MS/MS technique.The mRNA expressions of PDCD4 and the genes associated with cell inflammation and apoptosis were detected with RT-PCR,and the expressions of FIS1,DRP1 and OPA1 proteins key to mitochondrial fission and fusion were determined using Western blotting.JC-1 and MitoSOX fluorescent probes were used to observe the changes in mitochondrial membrane potential and mitochondrial reactive oxygen species levels under by a laser confocal microscope.Results LPS stimulation of the cells significantly increased the mRNA expressions of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and monocyte chemoattractant protein 1(MCP1)and enhanced the cellular expression of PDCD4(P<0.05).Proteomic analysis suggested a correlation between PDCD4 knockdown and changes in mitochondrial dynamics in the cells.LPS treatment significantly increased the expressions of mitochondrial fission proteins FIS1 and DRP1 and lowered the expression of the fusion protein OPA1 in the cells(P<0.05),causing also mitochondrial oxidative stress and reduction of the mitochondrial membrane potential(P<0.05).In HUVECs,treatment with FCCP significantly attenuated the protective effect of PDCD4 knockdown,which inhibited LPS-induced inflammation and oxidative stress and restored the balance between mitochondrial fission and fusion.Conclusion PDCD4 knockdown protects vascular endothelial cells against LPS-induced damages by repressing mitochondrial fission and oxidative stress,promoting mitochondrial fusion,and maintaining normal mitochondrial function.

Objective:To study the alveolar bone remodeling of maxillary anterior teeth after extraction treatment and 2-year recovery period in adolescent patients with maxillary anterior arch protrusion.Methods:15 adolescent patients with maxillary anterior arch protru-sion were included,2 maxillary first premolars were extracted and implant anchorage combined with sliding method were used to close the extraction gap.CBCT images were taken before treatment(T0),after treatment(T1)and 2 years of recorvery period(T2),respectively.After multi-plane reconstruction with Dophin Imaging,the alveolar bone area(ABA)changes of maxillary central incisor,lateral incisor and canine at cementoenamel junction(CEJ-3 mm),root neck,central part,and root tip were measured and recorded as TAC,TA1,TA2 and TA3 respectively.The labial palatal alveolar crest to CEJ bone height(BH)of each tooth was recorded as BCL,BCP respectively.The data were analyzed by IBM SPSS statistics 25.0.Results:In T0-T2 phase,TA1 of each tooth was reduced.In T0-T1 phase,the horizontal adsorption of teeth was significantly correlated with ΔBCP,followed by ΔTA3.In T0-T2 phase,ΔBCP,ΔTA2,ΔTA3 and the horizontal adsorption of teeth showed low negative correlation.In T0-T1 phase,the vertical reduction of teeth was significantly positively correlated with ΔTAC,followed by low correlation with ΔTA3 and ΔTA1.Conclusion:In the treatment of anterior arch protrusion after extraction correction in adolescent patients the more the vertical reduction and horizontal adsorption of teeth in the treatment phase,the more the alveolar bone thickness and height around the tooth root in the maintenance phase,which were significantly positively correlated.Reasonable control of the vertical move-ment of teeth in the alveolar bone can improve the periodontal condition around the teeth to a certain extent.

Bariatric surgery may cause intestinal microecological environment imbalance due to changes in gastrointestinal anatomy.Some patients may have compli-cations,even regain weight.Probiotics can act on intestinal mucosa,epithelium and gut-associated lymphoid tissue to improve the intestinal microecological environment of obese patients after bariatric surgery.Probiotics can promote the production of short-chain fatty acids,stimulate intestinal cells to release glucagon-like peptide-1,peptide tyrosine-tyrosine,insulin and other endocrine hormones,affect the function of the central nervous system through the gut-brain axis,make patients after bariatric surgery feel full,and reduce blood sugar at the same time.Probiotics can produce lactic acid,acetic acid and lactase,to inhibit the growth of harmful bacteria and to improve gastrointestinal symptoms of patients after bariatric surgery.Probiotics can activate the AMP-activated protein kinase signaling pathway,improve lipid metabolism,and promote the recovery of symptom indicators of nonalcoholic fatty liver disease after bariatric surgery.Probiotics can regulate the release of neurotransmitters or metabolites by the microbiota through the gut-brain axis to affect brain activity and behavior,thus helping patients improve negative emotions after bariatric surgery.This article describes the intestinal microecological environment of obese patients and mechanism of the change after bariatric surgery and summarizes the effects and possible mechanisms of probiotics in improving the intestinal microecological environment of obese patients after bariatric surgery,to provide references for promoting the clinical application of probiotics.

Objective:To examine the factors that contribute to memory impairment in elderly stroke patients and develop a predictive model.Methods:One hundred stroke patients from the First People's Hospital of Changzhou were selected to assess the incidence of memory impairment using the Montreal cognitive assessment memory index score(MoCA-MIS).Univariate analysis and multivariate Logistic regression were performed to determine the factors influencing memory impairment in these patients.Additionally, the correlation among relevant scale scores was examined, and a prediction model was developed.Results:In the study, 49 patients(49.0%)did not exhibit memory impairment.Patients with memory impairment were found to have higher proportions of individuals over 75 years old, elevated levels of triglyceride(TG), total cholesterol(TC), low-density lipoproteins cholesterol(LDL-C), and National Institute of Health Stroke Scale(NIHSS)scores compared to those without memory impairment.Conversely, patients without memory impairment had higher proportions of individuals with more than 9 years of education, higher levels of high-density lipoprotein cholesterol(HDL-C), mini-mental state examination(MMSE)scores, Rivermead behavioural memory test-Ⅱ(RBMT-Ⅱ)scores, and picture-based memory impairment screen(PMIS)scores(all P<0.05).Furthermore, Montreal cognitive assessment-memory index(MoCA-MIS)scores in stroke patients with memory impairment showed negative correlations with NIHSS scores, TG, and LDL-C, while showing positive correlations with HDL-C, MMSE scores, RBMT-Ⅱ scores, and PMIS scores(all P<0.05).Multifactorial Logistic regression analysis indicated that years of education, TG, HDL-C, NIHSS score, MMSE score, RBMT-Ⅱ score, PMIS score, and the location of the lesion in the cortex or temporal lobe were significant factors influencing memory impairment in stroke patients(all P<0.05).The receiver operating characteristic curve(ROC)analysis revealed an area under curve(AUC)of 0.955(95% CI: 0.921-0.977)for the prediction model of memory impairment in stroke patients, with a Yoden index of 0.841. Conclusions:The risk of memory impairment in stroke patients is associated with education years and blood lipid levels.Factors such as high education level, active cognitive function, and memory training serve as protective factors against memory impairment.The prediction model developed using these influencing factors demonstrates high predictive accuracy for post-stroke memory impairment.

Objective:To measure the crown conical degree of the remaining maxillary incisors in patients with congenital tooth agenesis, and to analyze the influence of different gene mutations on the crown conical degree of patients.Methods:Whole exome sequencing was performed on 85 patients with congenital tooth agenesis (50 males, 35 females, median age 19 years old) who visited the Department of Prosthodontics, Peking University School and Hospital of Stomatology from January 2019 to January 2023. The pathogenic gene was identified. The width of the crowns of the maxillary central and lateral incisors at the incisal 1/3 and gingival 1/3 were measured on the panoramic radiograph, and the ratio was defined as the crown conical degree. The smaller the ratio is, the more likely is the crown to be peg shaped teeth. The control group was matched by age and gender with 85 other patients with intact maxillary permanent incisors who were treated in the Department of Prosthodontics, Peking University School and Hospital of Stomatology from January 2019 to January 2023. The conical degree of the tooth agenesis group was compared with the control group by t-test, and the differences in the crown conical degree in different gene mutation groups were compared using one-way analysis of variance, and the multiple comparisons among gene groups were carried out using the LSD method.Results:Among the 85 tooth agenesis patients, the numbers of patients in each gene mutation group were 20 in ectodysplasin A (EDA) group, 8 in ectodysplasin A receptor (EDAR) group, 15 in wingless-type MMTV integration site family, member 10A (WNT10A) group, 16 in paired box 9 (PAX9) group, 10 in Msh homeobox 1 (MSX1) group, 10 in low-density lipoprotein receptor related protein 6 (LRP6) group, and 6 in bone morphogenetic protein4 (BMP4) group. The number of missing teeth were 1-27, median number 15 among the tooth agenesis patients. There was no significant difference in the conical degree between the left and right homonymous teeth in the congenital tooth agenesis group and the control group ( P>0.05). The crown conical degree of maxillary central incisor and lateral incisor in the congenital missing teeth group (0.95±0.24, 0.90±0.22) was significantly smaller than that in the control group (1.12±0.09, 1.13±0.09) ( t=-8.50, P<0.001; t=-11.47, P<0.001). In WNT10A mutants, the conical degree of lateral incisors (0.89±0.18) was less than that of central incisors (1.07±0.15)( t=3.68, P<0.001). The conical degree of central incisors and lateral incisors (0.70±0.23, 0.57±0.15) of EDA mutants was significantly lower than that in patients with other gene mutations ( P>0.05). Conclusions:Compared with the normal control group, the remaining maxillary central and lateral incisors of the seven gene mutation groups of patients with congenital tooth agenesis all had different degrees of conical crown. Among them, the crown conical degree of maxillary central and lateral incisors of the EDA mutation was the most severe, and the WNT10A mutation affected the maxillary lateral incisors more specifically.

Humans ; Diabetic Neuropathies/diagnostic imaging* ; Diabetes Mellitus, Type 2 ; Ultrasonography ; Diabetic Foot/diagnostic imaging*