Nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) is a cytosolic pattern recognition receptor that recognizes multiple pathogen-associated molecular patterns and damage-associated molecular patterns. It is a cytoplasmic immune factor that responds to cellular stress signals, and it is usually activated after infection or inflammation, forming an NLRP3 inflammasome to protect the body. Aberrant NLRP3 inflammasome activation is reportedly associated with some inflammatory diseases and metabolic diseases. Recently, there have been mounting indications that NLRP3 inflammasomes play an important role in liver injuries caused by a variety of diseases, specifically hepatic ischemia/reperfusion injury, hepatitis, and liver failure. Herein, we summarize new research pertaining to NLRP3 inflammasomes in hepatic injury, hepatitis, and liver failure. The review addresses the potential mechanisms of action of the NLRP3 inflammasome, and its regulation in these liver diseases.
Humans ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Inflammasomes/physiology* ; Animals ; Liver Diseases/metabolism* ; Liver/metabolism* ; Reperfusion Injury/metabolism*

Objective·To evaluate the applicability of dual-unit cantilever restorations supported by a single narrow-diameter implant for consecutive missing teeth in the anterior mandibular region.Methods·A simplified mandibular anterior jaw model and a dual-unit cantilever model supported by a single narrow-diameter implant were constructed.The dimensions of the mandibular anterior bone block were set to 20 mm(length),5 mm(width),and 15 mm(height).The narrow-diameter implant used was the Axiom 2.8 two-stage implant,2.8 mm× 10 mm,paired with a 2.5 mm straight abutment.Based on calculations,the edentulous gap ranged from 5.8 mm to 11.6 mm,leading to the creation of seven crown models with mesiodistal widths of 5.8,6.8,7.8,8.8,9.8,10.8,and 11.8 mm.The implant,crowns,and jaw model were assembled using Siemens Nx 12.0 software,and the data were imported into Ansys Workbench 18.0 for finite element analysis.A vertical load of 100 N and a 30° oblique load were applied to simulate occlusal forces.The Von-Mises stress on the implants,as well as the maximum compressive and tensile stresses in the cortical bone and the maximum tensile stress in the cancellous bone,was analyzed to investigate stress distribution under varying cantilever lengths.Results·The implant neck region exhibited the highest stress concentration.As the cantilever length increased,the peak Von-Mises stress on the implants,the maximum tensile stress in the cortical and cancellous bones,and the maximum compressive stress in the cortical bones all increased progressively.However,all stress values remained within physiological limits.The peak Von-Mises stress ranged from 141.52 MPa to 707.17 MPa,below the implant's ultimate tensile strength of 930 MPa.The maximum tensile stress in the cortical bones(with a peak of 60.82 MPa in the 11.8 mm group)was below the cortical bone's tensile strength limit of 100-130 MPa.The maximum compressive stress in the cortical bone(with an absolute maximum value of 129.39 MPa in the 11.8 mm group)was below the cortical bone's compressive strength limit of 170 to 190 MPa(absolute values).The maximum tensile stress in the cancellous bone ranged from 0.84 MPa to 4.70 MPa,which was below or close to its ultimate tensile strength of 2-5 MPa.Conclusion·Dual-unit cantilever restorations supported by a single narrow-diameter implant may represent a viable treatment option for consecutive missing teeth in the anterior mandibular region.

Objective·To evaluate the applicability of dual-unit cantilever restorations supported by a single narrow-diameter implant for consecutive missing teeth in the anterior mandibular region.Methods·A simplified mandibular anterior jaw model and a dual-unit cantilever model supported by a single narrow-diameter implant were constructed.The dimensions of the mandibular anterior bone block were set to 20 mm(length),5 mm(width),and 15 mm(height).The narrow-diameter implant used was the Axiom 2.8 two-stage implant,2.8 mm× 10 mm,paired with a 2.5 mm straight abutment.Based on calculations,the edentulous gap ranged from 5.8 mm to 11.6 mm,leading to the creation of seven crown models with mesiodistal widths of 5.8,6.8,7.8,8.8,9.8,10.8,and 11.8 mm.The implant,crowns,and jaw model were assembled using Siemens Nx 12.0 software,and the data were imported into Ansys Workbench 18.0 for finite element analysis.A vertical load of 100 N and a 30° oblique load were applied to simulate occlusal forces.The Von-Mises stress on the implants,as well as the maximum compressive and tensile stresses in the cortical bone and the maximum tensile stress in the cancellous bone,was analyzed to investigate stress distribution under varying cantilever lengths.Results·The implant neck region exhibited the highest stress concentration.As the cantilever length increased,the peak Von-Mises stress on the implants,the maximum tensile stress in the cortical and cancellous bones,and the maximum compressive stress in the cortical bones all increased progressively.However,all stress values remained within physiological limits.The peak Von-Mises stress ranged from 141.52 MPa to 707.17 MPa,below the implant's ultimate tensile strength of 930 MPa.The maximum tensile stress in the cortical bones(with a peak of 60.82 MPa in the 11.8 mm group)was below the cortical bone's tensile strength limit of 100-130 MPa.The maximum compressive stress in the cortical bone(with an absolute maximum value of 129.39 MPa in the 11.8 mm group)was below the cortical bone's compressive strength limit of 170 to 190 MPa(absolute values).The maximum tensile stress in the cancellous bone ranged from 0.84 MPa to 4.70 MPa,which was below or close to its ultimate tensile strength of 2-5 MPa.Conclusion·Dual-unit cantilever restorations supported by a single narrow-diameter implant may represent a viable treatment option for consecutive missing teeth in the anterior mandibular region.

Objective:To explore the feasibility and clinical efficacy of prone transpsoas lateral interbody fusion (PTP LIF) combined with posterior pedicle screw fixation for the treatment of lumbar degenerative diseases in the prone position.Methods:A total of 23 patients who underwent LLIF in the prone position at the First People's Hospital of Yunnan Province between March 2023 and October 2023 were retrospectively analyzed. The cohort comprised 9 males and 14 females, with a mean age of 55.5±8.8 years (range, 41-70 years). The clinical diagnoses included intervertebral disc herniation with endplate inflammation (3 cases), lumbar spinal stenosis (13 cases), lumbar spondylolisthesis (5 cases), and lumbar instability (2 cases). The surgical segments involved L 3, 4 (15 cases), L 4, 5 (6 cases), and L 3-L 5 (2 cases), with 21 cases involving a single segment and 2 cases involving double segments. The disc height and lumbar lordosis Angle before and after surgery were compared. Lower back pain was evaluated using the visual analogue scale (VAS), while lumbar spine function was assessed via the Oswestry Disability Index (ODI). Clinical efficacy was evaluated according to the modified MacNab criteria at the last follow-up. Results:All surgeries were successfully completed. The operation time was 120.2±21.4 min (range, 90-175 min), intraoperative blood loss was 131.1±40.8 ml (range, 60-200 ml), and the hospital stay was 6.2±1.6 days (range, 4-10 days). Follow-up was obtained for all 23 cases, with the follow-up time being 9.6±2.2 months (range, 6-13 months). One case of endplate damage occurred during surgery, two cases of transient psoas muscle weakness occurred postoperatively, and one case of lower limb pain and numbness was reported; no cases of wound infection or delayed healing were observed. The postoperative disc height improved compared to preoperative (6.8±1.9 mm; F=66.618, P<0.001). There was no statistically significant difference between 3 months postoperative (11.1±1.2 mm) and immediately postoperative (12.2±1.2 mm; P>0.05), but there was a statistically significant difference between the last follow-up (10.7±1.1 mm) and immediately postoperative ( P<0.05). The postoperative lumbar lordosis angle improved compared to preoperative (35.3°±5.4°; F=19.465, P<0.001), with no statistically significant difference between 3 months postoperative (44.1°±5.4°) and immediately postoperative (47.8°±6.6°; P>0.05), but there was a statistically significant difference between the last follow-up (43.2°±5.3°) and immediately postoperative ( P<0.05). The postoperative VAS score improved compared to preoperative (6.3±1.1 points; F=79.931, P<0.001), and the last follow-up (1.1±1.1 points) showed further improvement compared to 3 months postoperative (1.7±1.4 points; P<0.05). The postoperative ODI improved compared to preoperative (69.9%±7.4%; F=592.392, P<0.001), with 3 months postoperative (23.1%±3.1%) showing improvement compared to 1 month postoperative (29.2%±3.1%), and the last follow-up (17.5%±3.6%) showing further improvement compared to 3 months postoperative ( P<0.05). At the last follow-up, the modified MacNab criteria were: excellent in 16 cases, good in 5, fair in 2, with an excellent and good rate of 91% (21/23); 7 cases of cage subsidence were observed, with no cases of internal fixation loosening. Conclusion:PTP LIF combined with pedicle screw fixation for the treatment of lumbar degenerative diseases is safe and effective, with satisfactory short-term postoperative outcomes.

Objective·To explore the role of advanced platelet-rich fibrin(A-PRF)in osteochondral regeneration.Methods·Bone-marrow mesenchymal stem cells(BMSCs)and knee joint chondrocytes were obtained from New Zealand rabbits.A-PRF was obtained by low-speed centrifugation of the heart blood of rabbits.The histological structure of A-PRF was observed by an optical microscope.The release of growth factors in A-PRF was detected by ELISA,including platelet-derived growth factor,transforming growth factor-β,insulin-like growth factor,vascular endothelial growth factor,epidermal growth factor and fibroblast growth factor.A-PRF's cytotoxicity and capability for promoting the proliferation of rabbit BMSCs were detected by live/dead double staining and MTT methods.The effect of A-PRF on the gene expression of type Ⅱ collagen,aggrecan,alkaline phosphatase(ALP)and osteocalcin(OCN)in rabbit BMSCs was detected by real-time fluorescence quantitative polymerase chain reaction(qRT-PCR).Transwell chambers were used to determine the effect of A-PRF on the migration ability of rabbit BMSCs and the chondrocytes.Rabbit knee osteochondral defect models were established,and 18 rabbits were randomly divided into 3 groups.The A-PRF group(n=6)was implanted with A-PRF in the defect,the A-PRF+BMSCs group(n=6)was implanted with rabbit BMSCs on A-PRF,and the control group(n=6)did not undergo implantation.The rabbits were sacrificed 12 weeks after surgery and the knee joint specimens were stained with hematoxylin-eosin(H-E),toluidine blue and safranin O/fast green.Based on the surface morphology and histology of the knee joints,the International Cartilage Repair Society(ICRS)scoring system was used for macroscopic and histological scoring.Results·A-PRF had a loose network structure and can slowly release growth factors.No cytotoxicity to rabbit BMSCs was observed after adding A-PRF,and the the capability for promoting the proliferation of rabbit BMSCs was significantly increased at 24,48 and 72 h after adding A-PRF(all P<0.05).Chondrogenesis-related gene Ⅱ collagen and aggrecan,as well as osteogenesis-related genes ALP and OCN were significantly up-regulated(all P<0.05).After adding A-PRF,the migration abilities of rabbit BMSCs and chondrocytes were significantly enhanced(both P<0.05),and the migration ability of rabbit BMSCs was significantly higher than that of chondrocytes(P=0.025).The joint surface morphology in the rabbit knee joint defect models was observed.It can be seen that the defects in the A-PRF group and the A-PRF+BMSCs group were basically restored,while the the defects in the control group were only covered by soft tissue.In the ICRS macroscopic score,there was no statistical difference between the A-PRF group and the A-PRF+BMSCs group,but the scores of the two groups were all significantly higher than those of the control group(all P<0.05).According to the histological results,both the A-PRF group and the A-PRF+BMSCs group formed osteochondral repair,but the cartilage in the A-PRF group was more mature,while the control group formed fibrous repair.In the ICRS histological score,there was no statistical difference between the A-PRF group and the A-PRF+BMSCs group,but the scores of both the groups were significantly higher than those of the control group(both P<0.05).Conclusion·Autologous A-PRF has good biocompatibility and the capability for promoting the proliferation of BMSCs.It can promote the repair of cartilage and subchondral bone both in vitro and in vivo.

NAD(P)H: quinone oxidoreductase 1 (NQO1) is a flavin protease highly expressed in various cancer cells. NQO1 catalyzes a futile redox cycle in substrates, leading to substantial reactive oxygen species (ROS) production. This ROS generation results in extensive DNA damage and elevated poly (ADP-ribose) polymerase 1 (PARP1)-mediated consumption of nicotinamide adenine dinucleotide (NAD⁺), ultimately causing cell death. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD⁺ salvage synthesis pathway, emerges as a critical target in cancer therapy. The concurrent inhibition of NQO1 and NAMPT triggers hyperactivation of PARP1 and intensive NAD⁺ depletion. In this study, we designed, synthesized, and assessed a novel series of proqodine A derivatives targeting both NQO1 and NAMPT. Among these, compound T8 demonstrated potent antitumor properties. Specifically, T8 selectively inhibited the proliferation of MCF-7 cells and induced apoptosis through mechanisms dependent on both NQO1 and NAMPT. This discovery offers a promising new molecular entity for advancing anticancer research.
Humans ; NAD/metabolism* ; Cell Line, Tumor ; Reactive Oxygen Species/metabolism* ; Nicotinamide Phosphoribosyltransferase/metabolism* ; Cytokines/metabolism* ; Quinones ; Oxidoreductases

OBJECTIVE To establish the fingerprint of Sophora flavescens， and to screen differential components and determine their contents.　METHODS HPLC fingerprints of 12 batches of S. flavescens were established by using Similarity Evaluation System of Chromatographic Fingerprints of TCM （2012 edition）； common peaks were identified and their similarities were evaluated. Chemical pattern recognition analysis [cluster analysis （CA），principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）] were performed with SIMCA 14.1 and SPSS 23.0 software， and differential components which influenced the quality of S. flavescens were screen with variable importance in the projection（VIP）＞1 as standard. Meanwhile， the contents of 4 kinds of differential components were determined by the same HPLC method.　RESULTS There were 17 common peaks in the fingerprints of 12 batches of S. flavescens，and their similarities were all higher than 0.96. A total of 6 common peaks were identified， i.e. oxymatrine （peak 1）， oxysophocarpine （peak 2）， matrine （peak 10）， trifolirhizin （peak 14）， kurarinone （peak 16） and norkurarinone （peak 17）. Results of CA， PCA and OPLS-DA showed that 12 batches of S. flavescens were divided into 3 categories according to producing area， i.e. S1-S7 （Shangzhou District of Shaanxi Province） were grouped into one category， S8-S10 （Yichuan County of Henan Province） into one category and S11-S12 （Chifeng City of Inner Mongolia） into one category. VIPs of matrine， norkurarinone， kurarinone and oxysophocarpine and the chemical components represented by peak 11 and 9 were all greater than 1. The contents of matrine， norkurarinone， kurarinone and oxysophocarpine in 12 batches of S. flavescens were 2.65-4.93， 1.54-3.44， 9.63-12.94 and 5.08-6.10 mg/g， respectively. CONCLUSIONS HPLC fingerprint of S. flavescens is established successfully in the study， and can be used to screen 6 differential components by combining with chemical pattern recognition analysis， which can provide reference for quality control of S. flavescens.

Objective:To investigate the clinical efficacy of oblique lateral interbody fusion (OLIF) combined with lateral plate (LP) fixation and posterior lumbar interbody fusion (PLIF) combined with pedicle screw fixation in the treatment of adjacent segment disease (ASDis).Methods:Data of 21 ASDis patients treated with OLIF-LP from August 2016 to October 2019 were selected, including 9 males and 12 females; age was 59.3±7.0 years (range, 46-71 years). Target segments: L 2, 3 1 cases (4.8%), L 3, 4 16 cases (76.2%), L 4, 5 4 cases (19.1%). Twenty-one ASDis patients matched with age, sex and surgical segment and treated with PLIF were selected as the control group. The operation time, intraoperative bleeding, postoperative hospital stay, visual analogua scale (VAS), Oswestry disability index (ODI), disc height (DH), intervertebral foramen height (IFH) and lumbar lordosis (LL) were compared between the groups were tested by t-test. VAS score, ODI, DH, IFH and LL were compared within the group by ANOVA, and Bonferroni's test was used for pairwise comparison. Results:All of 42 patients were followed up for 23.7 ±7.4 months (range, 12-36 months). The operation time (97.6 ± 18.0 min) and interpretative bleeding (38.5±62.7 ml) in OLIF-LP group were significantly lower than those in PLIF group (operation time 154.6±42.4 min) and interpretative bleeding (288.6±55.3 ml). There were significant differences between two groups ( t=5.66, P<0.001; t=8.23, P<0.001); the postoperative hospital stay 4.4±1.3 d in OLIF-LP group was longer than that in PLIF group 5.1±1.2 d, but there was no significant difference ( t=1.93, P=0.061); VAS score in OLIF-LP group at 1 month and 3 months after operation (1.6 ± 0.9 points, 1.4 ± 0.8 points), and the ODI index (29.4%±4.7%) after one month operation was improved better than that of PLIF group ( t=2.48, P=0.017; t=2.35, P=0.024; t=2.28, P=0.029), but there was no significant difference between the 12 months after operation of two groups ( t=0.99, P=0.329; t=0.86, P=0.395). The immediately after operation, 3 months after operation and 12 months after operation of DH, IFH and LL in the two groups were significantly improved compared with those before operation ( P<0.05). The immediately after operation, 3 months after operation and 12 months after operation of DH and IFH in the OLIF-LP group were better than those in the PLIF group ( P<0.05), while LL had no significant difference ( P>0.05). There were 2 cases (9.52%) in each group with cage sinking, but no clinical symptoms occurred. In the OLIF-LP group, there was no injury of blood vessels, nerves or abdominal organs during operation, and 2 patients had transient lower limb pain after operation; In the PLIF group, 2 cases (9.52%) of dural rupture were repaired during operation, and no cerebrospinal fluid leakage occurred after operation; Postoperative lower limb pain was aggravated in 3 cases, and improved after dehydration, anti-inflammatory and analgesic treatment; 2 cases of incision exudation healed after symptomatic treatment. Conclusion:OLIF combined with LP fixation has the same clinical effect as PLIF in the treatment of lumbar ASDis, but OLIF combined with LP fixation has more advantages in surgical trauma, postoperative recovery and related complications.

Objective:To discuss the clinical effect about the external locking compression plate(LCP) combined with lower abdominal conjoined flap for fixing the open fracture and covering the soft tissue defects on tibia.Methods:From August 2017 to December 2020, 18 patients with serve tibial open fracture were admitted into the trauma center, including 15 males and 3 females with a median age of 38 (ranged, 25-58) years old. The etiology involving: 9 cases by traffic accident, 3 by downfall, 6 by crushing, which classified as type III B( n=6) and III C( n=12) by the Anderson-Gustilo criterion. All wounds were taken radical debridement, fixed by the femur LCP and covered by the VSD during the emergency operation. The lower abdominal conjoined flap was dissected to cover the soft tissue defect, of which the dimension and pedicle length were tailored to the defect. Primary closure was performed on the donor site. Followed-up was conducted by telephone and WeChat. Results:One flap was changed to gastrocnemius myocutaneous flap because of the venous crisis. Seventeen flaps survived completely without significant complications. All the donor and recipient sites had primary healing. A mean follow-up of 15 (ranged, 12 to 18) months. The fracture healed without bone infection and bone nonunion. The aesthetic outcomes were satisfied without overgrown hairy and hyperpigmentation for all flaps. The concealed linear scar was left without hernia or other morbidity on the donor site. At the final follow-up, 12 cases were excellent and 6 cases were good evaluated by the Johner-Wruhs criteria.Conclusion:The external LCP can immobilise the knee and ankle joint with the preservation of the soft tissue, and the free lower abdominal conjoined flap was useful for covering extreme defects with concealed donor site, with enough tissue volume. The combination of both could lower the postoperative infection, reduce the operation time and shorten the hospital stay.