Inflammation plays a pivotal role in the etiology and progression of various diseases. In traditional Chinese medicine, the whole plants of Thesium chinense Turcz. and its preparations (e.g. Bairui Granules) have been employed to manage inflammatory conditions. While flavonoids were previously considered the primary anti-inflammatory components, other potentially active constituents have been largely overlooked and not thoroughly investigated. This study presents a novel finding that the total alkaloids of T. chinense (BC-Alk) are potent active substances underlying the traditional and clinical applications of T. chinense and Bairui Granules as anti-inflammatory agents. UPLC-MS/MS analysis identified the composition of BC-Alk as quinolizidine alkaloids. The anti-inflammatory efficacy of BC-Alk was evaluated using a lipopolysaccharide (LPS)-induced lung inflammation model in mice. Results demonstrated that BC-Alk significantly mitigated LPS-induced lung inflammation, attenuated the overproduction of IL-1β and the overproduction of inflammatory factors (TNF-α), and ameliorated lung tissue hyperplasia in mice in vivo. Mechanistic studies in vitro revealed that BC-Alk upregulated the expression of Nrf2 and its downstream proteins NQO1 and glutamate-cystine ligase and modifier subunit (GCLM), inhibited NF-κB phosphorylation, and suppressed NLRP3 activation. Collectively, these findings indicate that BC-Alk exerts potent inhibitory effects against lung inflammation by modulating Nrf2, NF-κB, and NLRP3 pathways. This study provides new insights into the anti-inflammatory constituents of T. chinense and Bairui Granules.
Animals ; Lipopolysaccharides/adverse effects* ; Alkaloids/pharmacology* ; NF-kappa B/metabolism* ; NF-E2-Related Factor 2/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Mice ; Signal Transduction/drug effects* ; Anti-Inflammatory Agents/pharmacology* ; Male ; Mice, Inbred C57BL ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Pneumonia/genetics*

Endovascular treatment has become the standard treatment method for acute ischemic stroke caused by large vessel occlusion. The application of neuroimaging techniques for appropriate patient selection and prognosis prediction is of great significance for successful endovascular treatment. This article reviews the application progress of fluid-attenuated inversion recovery sequence vascular hyperintensity in patients with acute ischemic stroke underwent endovascular treatment.

Objective:To explore the effects of early debridement and conservative eschar removal followed by wound coverage with acellular dermal matrix (ADM), i.e., early surgery, in the treatment of children with deep burns.Methods:This study was a retrospective cohort study. From January 2017 to December 2022, 278 deep burned hospitalized children aged 1-7 years who met the inclusion criteria were admitted to Central Hospital Affiliated to Shandong First Medical University. According to the differences in treatment processes, 134 children who underwent early surgery+routine dressing change were enrolled in eschar removal+dressing change group (77 males and 57 females, aged 1 (1, 2) years), and 144 children who underwent only routine dressing change were enrolled in dressing change alone group (90 males and 54 females, aged 1 (1, 2) years). Fifty-one children without full-thickness burns in eschar removal+dressing change group were enrolled in eschar removal+dressing change group 1 (26 males and 25 females, aged 1 (1, 2) years), and 57 cases of the 83 children with full-thickness burns who did not undergo autologous skin grafting at the same time of early surgery (namely early skin grafting) in eschar removal+dressing change group were included in eschar removal+dressing change group 2 (37 males and 20 females, aged 1 (1, 2) years). Seventy-six children without full-thickness burns in dressing change alone group were included in dressing change alone group 1 (51 males and 25 females, aged 1 (1, 3) years), and 68 children with full-thickness burns in dressing change alone group were included in dressing change alone group 2 (39 males and 29 females, aged 1 (1, 2) years). For deep partial-thickness burn wounds and small full-thickness burn wounds in eschar removal+dressing change group, the eschar removal was performed on the basis of retaining a thin layer of denatured dermis so as to preserve the healthy tissue of the wound base, and ADM was applied to all wounds externally after eschar removal. For larger full-thickness burn wounds in this group, especially those located in the functional part of joints, eschar removal to the plane layer of viable tissue and early autologous skin grafting was needed. When the superficial wounds of children healed or tended to heal, the residual wounds were evaluated, and elective autologous skin grafting was performed if it was difficult to heal within 14 days. The healing time, intervention healing time, times of operation/dressing change, and times of intervention operation/dressing change in children with deep partial-thickness burn wounds of children in eschar removal+dressing change group, dressing change alone group, eschar removal+dressing change group 1, and dressing change alone group 1 were recorded. At the last follow-up (follow-up period was set to 7-12 months), the modified Vancouver scar scale (mVSS) scores of the most severe area of scar hyperplasia of healed deep partial-thickness burn wounds of 54 children in eschar removal+dressing change group and 48 children in dressing change alone group were recorded. The healing time and times of operation/dressing change of all burn wounds of children in eschar removal+dressing change group and dressing change alone group, and the healing time and times of operation/dressing change of full-thickness burn wounds of children in eschar removal+dressing change group 2 and dressing change alone group 2 were recorded. The incidences of wound infection, sepsis, fever, and fever after 5 days of burns in children of eschar removal+dressing change group and dressing change alone group during wound healing.Results:Compared with those in dressing change alone group, the healing time and intervention healing time were significantly shortened, and the times of operation/dressing change and times of intervention operation/dressing change were significantly reduced in children with deep partial-thickness burn wounds in eschar removal+dressing change group (with Z values of -11.00, -11.33, -12.64, and -11.65, respectively, P<0.05). Compared with those in dressing change alone group 1, the healing time and intervention healing time were significantly shortened, and the times of operation/dressing change and times of intervention operation/dressing change were significantly reduced in children with deep partial-thickness burn wounds in eschar removal+dressing change group 1 (with Z values of 6.57, 6.46, 8.04, and 6.57, respectively, P<0.05). At the last follow-up, the mVSS score of the most severe scar hyperplasia area of healed deep partial-thickness burn wounds of 54 children in eschar removal+dressing change group was 4.00 (3.00,5.00), which was significantly lower than 6.50 (5.00,7.00) of 48 children in dressing change alone group ( Z =-4.67, P<0.05).Compared with those in dressing change alone group, the healing time was significantly shortened, and times of operation/dressing change was significantly reduced in all burn wounds in eschar removal+dressing change group (with Z values of -5.20 and -6.34, respectively, P<0.05). Compared with those in dressing change alone group 2, the healing time was significantly shortened, and times of operation/dressing change was significantly reduced in full-thickness burn wounds in eschar removal+dressing change group 2 (with Z values of -5.22 and -5.73, respectively, P<0.05). During wound healing, the probabilities of fever and fever after 5 days of burns in children of eschar removal+dressing change group were significantly lower than those in dressing change alone group (with χ2 values of 4.13 and 3.91, respectively, P<0.05); only 1 child in dressing change alone group developed sepsis, and there was no statistically significant difference in the wound infection rate of children in the two groups ( P>0.05). Conclusions:For children with deep burns, early surgery, and early skin grafting or elective autologous skin grafting as needed, have better short-term and long-term effects than those without early surgery.

Objectives:To explore the relationship between pelvic rotation,osteotomy site and osteotomy angle in patients with thoracolumbar kyphosis of ankylosing spondylitis(AS).Methods:13 AS patients with thoracolumbar kyphosis,who underwent double-level pedicle subtraction osteotomy(PSO)between August 2017 and April 2021,were retrospectively analyzed.There were 11 males and 2 females,aged 43.5±8.5 years(29-58 years).A total of 26 PSO osteotomy were performed.The osteotomy angle was 35.6°±9.0°,the operative time was 434.2±117.1min,and the intraoperative blood loss was 2480.5±1486.3mL.The follow-up time was 29.0±4.0months(24-38months).The global kyphosis(GK),thoracic kyphosis(TK),lumbar lordosis(LL),sagittal vertical axis(SVA),horizontal distance between hip axis and hilus pulmonis(HDHH),pelvic tilt(PT),sacral slope(SS),and pelvic incidence(PI)were measured on the preoperative,two weeks postoperative,and final follow-up full-length lateral radiographs of the spine.The changes in PT(ΔPT)at two weeks after operation and final follow-up from the preoperative PT value were recorded,namely,postoperative pelvic rotation angle,which were recorded as two weeks-postoperative ΔPT and final follow-up ΔPT,respectively.The osteotomy angle was measured and recorded on the thoracolumbar CT two weeks after operation.The distances and angles between hip axis(HA),hilus pulmonis(HP)and the osteotomy apex were measured in the plane coordinate axis with the hip axis as the origin established on the preoperative full-length lateral spine X-ray film.The coordinate of the apex and the distances to and angles with HA and HP were used to represent the osteotomy site.The functional relationship between the pelvic rotation angle and the osteotomy site and osteotomy angle was calculated,and the ΔPT value calculated by the formula was obtained.Paired t test was used to verify the accuracy of the formula by comparing the ΔPT calculated by the formula with the ΔPT of 2 weeks after operation and the ΔPT of the final follow-up.Results:The GK,LL,SVA,HDHH,SS,and PT were 94.8°±15.1°,-17.0°±24.9°,29.4±6.9cm,10.3±8.8cm,5.7°±10.3°,and 43.6°±14.5°,respectively before operation,which were 34.0°±18.5°,34.1°±15.1°,10.4±4.5cm,1.7±4.7cm,24.6°±7.1°,and 24.5°±8.3°two weeks after operation,and 34.2°±18.0°、36.9°±19.4°、9.8±4.0cm、1.2±3.3cm、24.8°±7.3°,and 25.1°±7.8°at final follow-up.The above indexes two weeks after operation were significantly different from those before operation(P＜0.05).The TK and PI were 51.6°±19.4°and 49.3°±10.5°before operation,and 45.8°±18.7°and 48.8°±12.0°two weeks after surgery,with no significant difference(P＞0.05).There was no significant difference in GK,TK,LL,SVA,HDHH,PI,SS,and PT between two weeks after operation and final follow-up(P＞0.05).The formula-calculated ΔPT,two-weeks postoperative ΔPT,and final follow-up ΔPT were 17.8°±8.9°,19.2°±8.6°,and 18.5°±8.4°,respectively,with no significant statistical differences between(P＞0.05).Conclusions:There is an function relationship between the pelvic rotation after osteotomy in AS patients with thoracolumbar kyphosis and the site and angle of osteotomy.

Objectives:To explore the relationship between pelvic rotation,osteotomy site and osteotomy angle in patients with thoracolumbar kyphosis of ankylosing spondylitis(AS).Methods:13 AS patients with thoracolumbar kyphosis,who underwent double-level pedicle subtraction osteotomy(PSO)between August 2017 and April 2021,were retrospectively analyzed.There were 11 males and 2 females,aged 43.5±8.5 years(29-58 years).A total of 26 PSO osteotomy were performed.The osteotomy angle was 35.6°±9.0°,the operative time was 434.2±117.1min,and the intraoperative blood loss was 2480.5±1486.3mL.The follow-up time was 29.0±4.0months(24-38months).The global kyphosis(GK),thoracic kyphosis(TK),lumbar lordosis(LL),sagittal vertical axis(SVA),horizontal distance between hip axis and hilus pulmonis(HDHH),pelvic tilt(PT),sacral slope(SS),and pelvic incidence(PI)were measured on the preoperative,two weeks postoperative,and final follow-up full-length lateral radiographs of the spine.The changes in PT(ΔPT)at two weeks after operation and final follow-up from the preoperative PT value were recorded,namely,postoperative pelvic rotation angle,which were recorded as two weeks-postoperative ΔPT and final follow-up ΔPT,respectively.The osteotomy angle was measured and recorded on the thoracolumbar CT two weeks after operation.The distances and angles between hip axis(HA),hilus pulmonis(HP)and the osteotomy apex were measured in the plane coordinate axis with the hip axis as the origin established on the preoperative full-length lateral spine X-ray film.The coordinate of the apex and the distances to and angles with HA and HP were used to represent the osteotomy site.The functional relationship between the pelvic rotation angle and the osteotomy site and osteotomy angle was calculated,and the ΔPT value calculated by the formula was obtained.Paired t test was used to verify the accuracy of the formula by comparing the ΔPT calculated by the formula with the ΔPT of 2 weeks after operation and the ΔPT of the final follow-up.Results:The GK,LL,SVA,HDHH,SS,and PT were 94.8°±15.1°,-17.0°±24.9°,29.4±6.9cm,10.3±8.8cm,5.7°±10.3°,and 43.6°±14.5°,respectively before operation,which were 34.0°±18.5°,34.1°±15.1°,10.4±4.5cm,1.7±4.7cm,24.6°±7.1°,and 24.5°±8.3°two weeks after operation,and 34.2°±18.0°、36.9°±19.4°、9.8±4.0cm、1.2±3.3cm、24.8°±7.3°,and 25.1°±7.8°at final follow-up.The above indexes two weeks after operation were significantly different from those before operation(P＜0.05).The TK and PI were 51.6°±19.4°and 49.3°±10.5°before operation,and 45.8°±18.7°and 48.8°±12.0°two weeks after surgery,with no significant difference(P＞0.05).There was no significant difference in GK,TK,LL,SVA,HDHH,PI,SS,and PT between two weeks after operation and final follow-up(P＞0.05).The formula-calculated ΔPT,two-weeks postoperative ΔPT,and final follow-up ΔPT were 17.8°±8.9°,19.2°±8.6°,and 18.5°±8.4°,respectively,with no significant statistical differences between(P＞0.05).Conclusions:There is an function relationship between the pelvic rotation after osteotomy in AS patients with thoracolumbar kyphosis and the site and angle of osteotomy.

This study aimed to evaluate the therapeutic potential of inhibiting protein arginine methyltransferase 5(PRMT5)in cisplatin-induced hearing loss.The effects of PRMT5 inhibition on cisplatin-induced auditory injury were determined using immunohistochemistry,apoptosis assays,and auditory brainstem response.The mechanism of PRMT5 inhibition on hair cell survival was assessed using RNA-seq and Cleavage Under Targets and Tagment-quantitative polymerase chain reaction(CUT&Tag-qPCR)analyses in the HEI-OC1 cell line.Pharmacological inhibition of PRMT5 significantly alleviated cisplatin-induced damage to hair cells and spiral ganglion neurons in the cochlea and decreased apoptosis by protecting mitochondrial function and preventing the accumulation of reactive oxygen species.CUT&Tag-qPCR analysis demonstrated that inhibition of PRMT5 in HEI-OC1 cells reduced the accumulation of H4R3me2s/H3R8me2s marks at the promoter region of the Pik3ca gene,thus activating the expression of Pik3ca.These findings suggest that PRMT5 inhibitors have strong potential as agents against cisplatin-induced ototoxicity and can lay the foundation for further research on treatment strategies of hearing loss.

Radiotherapy is widely used in the management of advanced colorectal cancer (CRC). However, the clinical efficacy is limited by the safe irradiated dose. Sensitizing tumor cells to radiotherapy via interrupting DNA repair is a promising approach to conquering the limitation. The BRCA1-BARD1 complex has been demonstrated to play a critical role in homologous recombination (HR) DSB repair, and its functions may be affected by HERC2 or BAP1. Accumulated evidence illustrates that the ubiquitination-deubiquitination balance is involved in these processes; however, the precise mechanism for the cross-talk among these proteins in HR repair following radiation hasn't been defined. Through activity-based profiling, we identified PT33 as an active entity for HR repair suppression. Subsequently, we revealed that BAP1 serves as a novel molecular target of PT33 via a CRISPR-based deubiquitinase screen. Mechanistically, pharmacological covalent inhibition of BAP1 with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction, interrupting HR repair. Consequently, PT33 treatment can substantially enhance the sensitivity of CRC cells to radiotherapy in vitro and in vivo. Overall, these findings provide a mechanistic basis for PT33-induced HR suppression and may guide an effective strategy to improve therapeutic gain.

Cisplatin-related ototoxicity is a critical side effect of chemotherapy and can lead to irreversible hearing loss. This study aimed to assess the potential effect of the DNA methyltransferase (DNMT) inhibitor RG108 on cisplatin-induced ototoxicity. Immunohistochemistry, apoptosis assay, and auditory brainstem response (ABR) were employed to determine the impacts of RG108 on cisplatin-induced injury in murine hair cells (HCs) and spiral ganglion neurons (SGNs). Rhodamine 123 and TMRM were utilized for mitochondrial membrane potential (MMP) assessment. Reactive oxygen species (ROS) amounts were evaluated by Cellrox green and Mitosox-red probes. Mitochondrial respiratory function evaluation was performed by determining oxygen consumption rates (OCRs). The results showed that RG108 can markedly reduce cisplatin induced damage in HCs and SGNs, and alleviate apoptotic rate by protecting mitochondrial function through preventing ROS accumulation. Furthermore, RG108 upregulated BCL-2 and downregulated APAF1, BAX, and BAD in HEI-OC1 cells, and triggered the PI3K/AKT pathway. Decreased expression of low-density lipoprotein receptor-related protein 1 (LRP1) and high methylation of the LRP1 promoter were observed after cisplatin treatment. RG108 treatment can increase LRP1 expression and decrease LRP1 promoter methylation. In conclusion, RG108 might represent a new potential agent for preventing hearing loss induced by cisplatin via activating the LRP1-PI3K/AKT pathway.

Objective To assess the influencing factors of interdialysis blood pressure variability (BPV) in maintenance hemodialysis (MHD) patients from Pearl River Delta,and provide clinically useful information for the prevention and treatment of BPV.Methods MHD patients in 10 hemodialysis centers from Pearl River Delta were enrolled and analyzed retrospectively.According to the quartile of interdialysis systolic blood pressure-coefficient of variation (SBP-CV),patients were divided into four groups,and clinical data,biochemical indicators and drug use were compared among 4 groups.Binary logistic regression analysis was used to analyze the associated factors of interdialysis BPV.Results A total of 1010 MHD patients (612 males and 398 females) with the age of (56.3±13.9) years were enrolled in this study.Their dialysis duration was (48.4±36.1) months,and the median of interdialysis SBP-CV was 8.07％ (5.72％,11.34％).According to the quartile of SBP-CV,the patients were divided into four groups:low BPV group (SBP-CV≤5.72％,253 cases),middle BPV group (5.72％ ＜ SBP-CV≤8.07％,252 cases),high BPV group (8.07％ ＜ SBP-CV≤11.34％,253 cases) and extremely high BPV group (SBP-CV ＞ 11.34％,252 cases),and the dialysis duration,diabetes,ultrafiltration,interdialysis weight gain rate (IDWGR),serum calcium and the proportion of calcium channel antagonist used in the 4 groups were significantly different (all P ＜ 0.05).Logistic multiple regression analysis showed that high IDWGR (OR=1.216,95％CI 1.108-1.435,P ＜ 0.001) was an independent risk factors for interdialysis BPV in MHD patients,while high ultrafiltration volume (OR=0.436,95％CI 0.330-0.575,P ＜ 0.001) and calcium channel antagonists used (OR=0.686,95％CI 0.477-0.986,P=0.042) were independent protective factors.Conclusion High IDWGR is an independent risk factor for interdialysis BPV in MHD patients,while high ultrafiltration volume and calcium channel antagonists used are protective factors for interdialysis BPV in MHD patients.

Objective: To investigate the value of next-generation sequencing (NGS) technology in the prognosis monitoring and treatment guidance for molecular minimal residual disease (MRD) in acute myeloid leukemia (AML) patients with complete remission (CR). Methods: The clinical data of 68 AML (non-acute promyelocytic leukemia) patients who received gene mutation spectrum by using NGS technology at initial diagnosis and in CR phase in Tangdu Hospital of Air Force Military Medical University from January 2016 to July 2018 were retrospectively analyzed. The recurrence and survival of both molecular MRD positive group and negative group were analyzed and compared, and the value of NGS technology and multiparameter flow cytometry (MFC) were also analyzed in MRD monitoring. Results: There were 39 males (57.4%) and 29 females (42.6%) in 68 patients, and the median age was 52 years old (8-82 years old). Molecular MRD positive group included 38 patients, while negative group included 30 patients. Residual mutation gene type in CR phase was most frequently detected in epigenetic regulator gene mutations, such as ASXL1, TET2, DNMT3A and IDH1/IDH2. Statistical analysis showed that the 2-year cumulative recurrence rate (CIR) in the molecular MRD positive group was higher than that in the molecular MRD negative group (86.8% vs. 51.3%; χ² = 9.249, P = 0.002); the 2-year relapse-free survival (RFS) rate in the molecular MRD positive group was lower than that in the molecular MRD negative group (13.2% vs. 48.7%; χ² = 9.249, P = 0.002); the 2-year overall survival (OS) rate in the molecular MRD positive group was lower than that in the molecular MRD negative group (58.0% vs. 100%; χ² = 4.122, P = 0.042). Up to follow-up date, 3 patients with molecular MRD positive and 1 patient with molecular MRD negative who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) were still in disease-free survival. The results of monitoring MRD showed high consistency (76.7%, 33/43) in NGS and MFC. Compared with the other groups, the patients with both positive NGS and MFC had a higher relapse rate, and the difference was statistically significantly (P < 0.05). Conclusions Molecular MRD of AML patients is detected by using NGS technology, which could be used to predict the relapse and survival, suggesting that molecular MRD may guide post-remission treatment regimens and the determination of allo-HSCT indications.