Elevated glucose metabolism is a prominent characteristic of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA). However, the efficacy of inhibiting a single target of glucose metabolism in FLS using small molecular inhibitors is limited for RA treatment. Herein, the synergistic inhibition of FLS' survival, proliferation, and activation by combining two glucose metabolism inhibitors, diclofenac (DC) and lonidamine (LND) was first verified. Subsequently, DC and LND were individually conjugated to cystamine-modified hyaluronic acid (HA) to prepare two polymer-prodrug conjugates. A HAP-1 peptide-modified dual polymer-prodrug conjugates-assembled nanoparticles system (^HAP-1NP_DC+LND) was further tailored in the optimal synergistic ratio for targeted and synergistic metabolic modulation of FLS to alleviate RA symptoms. Upon targeted uptake by FLS in inflamed joints, ^HAP-1NP_DC+LND released DC and LND within the intracellular reductive microenvironment, where DC hinders glucose uptake and LND suppresses glycolytic enzymes to eliminate FLS synergistically. Additionally, the secretion of lactic acid and pro-inflammatory factors from FLS were reduced, thereby disrupting the crosstalk between FLS and pro-inflammatory macrophages. Finally, ^HAP-1NP_DC+LND demonstrated promising efficacy in a mouse model of collagen-induced arthritis (CIA). Overall, this research provides valuable insights into novel therapeutic strategies for the safe and effective of treatment RA through targeted and synergistic metabolic modulation of FLS.

Objective:To investigate the effect of zirconia personalized gingival structure on peri-implant soft and hard tissue stability after single-tooth implant restorations in patients with thin gingival biotypes in the anterior region, with a view to provide a clinical guideline.Methods:This retrospective study included 20 patients with thin gingival biotype and implant restorations in the anterior region. These patients included 9 males and 11 females, and the age was (35.2± 10.3) years. The patients were from the Department of Periodontal Implantology, Stomatology Hospital, Southern Medical University from January 2018 to December 2022. Computer-aided design/computer-aided manufacturing (CAD/CAM) techniques were used to fabricate a titanium base zirconia personalized gingival structure to maintain the soft-tissue perforated gingival contour of the anterior esthetic zone. This structure consists of two modalities: titanium base + zirconia outer crown or titanium base personalized zirconia abutment + zirconia outer crown. Clinical outcomes were recorded immediately and after delivery of the final restorations. Implant retention was recorded, esthetic scoring was performed using the pink esthetic index, the amount of bone resorption at the implant margins was measured based on digitized apical radiographs, and periodontal health was evaluated using the modified plaque index and the modified bleeding index.Results:The survival rate of the 20 implants was 100% after 3 years of wearing the final restorations, with a pink aesthetic score of 9.3±0.9. Bone resorption at the proximal and distal mesial margins of the implants was 0.09 (-0.21, 0.20) mm, 0.17 (-0.12, 0.27) mm after 3 years, respectively, and the difference was not statistically significant when compared to bone resorption immediately after placement of the final restoration [0(0, 0) mm] ( Z=-1.03, P=0.394; Z=-2.05, P=0.065). Conclusions:Zirconia personalized gingival structure maintains the stability of peri-implant hard and soft tissues of thin gingival biotypes in the anterior region.

Objective: On the basis of the dominant frequency index of functional connectivity, the "brain age" analysis method was used to explore abnormal development patterns of sensorimotor networks in boys with autism spectrum disorder(ASD). Methods: The resting state functional magnetic resonance data (7-12 years old) for 105 boys with ASD and 102 matched boys with normal development from the ABIDE public database were screened. Functional connection networks in different frequency bands of sensorimotor related brain regions were constructed for each individual, and the frequency of the strongest connection were constructed as the optimal frequency of the connection. Brain age analysis was used to explore the difference between brain age and chronological age in boys with ASD. Results: The brain sensorimotor network of boys with ASD showed an abnormal development pattern of overdevelopment followed by underdevelopment, and the transition between the two patterns occurred at approximately 7.8 years of age. Older boys with ASD (older than 10 years) whose underdevelopment trend was suppressed had lower ASD severity( r=-0.43, P < 0.05 ). Conclusion The brain sensorimotor network in boys with ASD has an abnormal development process, and the brain chronological age difference in the sensorimotor network has potential as a neuroimaging marker to measure the development of ASD.

After tooth extraction, labial contour collapses due to inevitable physiologic bone remodeling. To achieve optimal outcomes for pink esthetic treatment at anterior implant sites, bone or soft tissue augmentation has been advocated to maintain or reconstruct the labial tissue contour. When choosing soft tissue augmentation for esthetic restoration, it is necessary to strictly grasp the indications for surgery. Soft tissue augmentation to maintain or reconstruct the labial tissue contour could be considered in patients with healthy soft tissue and no bone defects or only mild horizontal bone defects. In immediate, early and late implant placement, the timing of soft tissue augmentation may vary. In immediate implantation, the labial bone plate is intact, so it is highly recommended to simultaneously manage soft tissue during implant placement. However, patients may have large bone defects with early or late implant placement. The risk of augmenting bone and soft tissue simultaneously is likely too high, and bone augmentation surgery is often performed at the first stage while soft tissue augmentation surgery is performed at the second stage. Therefore, soft tissue surgery is often carried out simultaneously with abutment connection. Currently, soft tissue augmentation is achieved mostly with adjacent autologous soft tissue grafts, such as free gingival grafts, subepithelial connective tissue grafts or pedicle palatal flaps, which are often accompanied by a second surgical area. The replacement of autogenous soft tissue grafting with new biological materials will become an inevitable trend. In this article, we analyze and summarize the indications, timing and different methods of soft tissue augmentation to maintain and reconstruct the labial contour.

OBJECTIVE: This study aimed to evaluate the clinical effect of periodontal microscopic surgery on the augmentation of attached gingiva and determined the clinical principle on how to use minimally invasive surgery to improve the surgery success rate. METHODS: Twenty patients with insufficient attached gingiva around implants were selected. Periodontal microscopic surgery for free gingival graft was performed to increase the width of the attached gingiva around the implants. The survival state of the free gingiva was observed after surgery, and the width of the attached gingiva around the implants was recorded before and after surgery and 1 year after surgery. The shrinkage rate of the free gingival flap 1 year after surgery was analyzed to evaluate the stability of the flap. RESULTS: The flaps of the 20 cases all survived. One year after the operation, the width of the attached gingiva was (3.05±0.44) mm, which increased compared with that of preoperation (2.56±0.31) mm
and decreased compared with that of postoperative day (2.13±0.28) mm. The shrinkage rate of the attached gingiva was 41.22%±5.04%. CONCLUSIONS The application of microscopic surgery on the augmentation surgery of attached gingiva can increase the success rate and improve the quality and quantity of attached gingiva around implants.
Dental Implants ; Gingiva ; surgery ; Humans ; Microsurgery ; Oral Surgical Procedures ; Surgical Flaps

Objective To investigate the effect of emodin on insulin resistance and serum inflammatory factors in obese rats. Methods 16 obese rats with experimental periodontitis were selected and then randomly di-vided into periodontal treatment group(control group)and periodontal therapy combined with emodin group(medi-cation group). All the rats were sacrificed 2 weeks after treatment. Before the rats were killed,the orbital vein blood was taken to detect fasting blood glucose,fasting insulin;levels of serum C-reactive protein(CRP)and tu-mor necrosis factor-α(TNF-α)were detected by enzyme linked immunosorbent assay.Results 2 weeks after peri-odontal treatment,level of CRP was significantly lower in the medication group than in the control group(t =2.170,P = 0.044);TNF-α was significantly lower in the medication group than in the control group(t = 3.074, P=0.007).Fasting blood glucose level was lower in the medication group than in the control group,and HOMA-β was higher than the control group,no statistical differences were found between the two groups.Conclusions Non-surgical periodontal treatment combined with local administration of emodin can help repair of periodontal epitheli-al barrier and reduce levels of serum inflammatory factors.

OBJECTIVE:To systematically review the effectiveness and safety of combination prescription of lidocaine with ropivacaine for anesthesia,and provide evidence-based reference for developing new compound preparation. METHODS:Retrieved from CJFD,Wanfang Database,VIP,PubMed and EBSCO,randomized controlled trials (RCT) about lidocaine combined with ropivacaine versus lidocaine alone or ropivacaine alone for anesthesia were collected. Meta-analysis was performed by using Rev Man 5.0 software provided by the Cochrane Collaboration after data extracting and quality evaluating. RESULTS:Totally 30 RCT were included,involving 2 442 patients. Results of Meta-analysis showed,lidocaine+ropivacaine vs. lidocaine:onset time was 6.77 min vs. 7.11 min [MD=-0.29,95%CI(-0.43,-0.16),P<0.001],maintenance time was 5.11 h vs. 2.11 h [MD=3.13,95%CI (3.02,3.25),P<0.001] and the incidence of adverse reactions was 28.6% vs. 44.6% [MD=0.43,95%CI(0.31,0.62),P<0.001];lidocaine+ropivacaine vs. ropivacaine:onset time was 9.49 min vs. 15.85 min [MD=-4.43,95%CI(-4.63,-4.22),P<0.001];maintenance time was 4.84 h vs. 6.79 h [MD=-0.61,95%CI(-0.71,-0.51),P<0.001];the incidence of adverse reac-tions was 44.8% vs. 48.1% [MD=0.82,95%CI(0.56,1.19),P=0.30]. Sensitivity analysis showed that the results were in stabili-ty. CONCLUSIONS:Lidocaine combined with ropivacaine shows rapid onset and long duration in anesthesia,and it can reduce ad-verse reactions play their respective advantages.

Objective We previously demonstrated that peroxiredoxin 3 (PRX3) was overexpressed in cervical cancer and the expression of PRX3 was positively associated to that of oncogenes E6/E7 of human papillomaviruses (HPV) type 16.The present study was conducted to investigate the link between HPV oncogenes and PRX3,which would be helpful to understanding the mechanism for cervical carcinogenesis.Methods Cervical epithelial cells were cultured and were transfected with recombinant pcDNA3.1 vector containing HPV16 E6/E7.The changes of PRX3 expression were detected by quantitative real time PCR and Western blotting.Results In the epithelial cells which stably expressed HPV16 E6/E7,the expression of PRX3 was significantly down-regulated at both mRNA and protein levels compared to that in the control cells.Conclusion Integration of high risk HPV DNA into the chromosomes of cervical epitheliums induced the change of the PRX3 expression,which might be involved in the initiation of cervical cancer.

Objective To investigate analgesic effects of the selective blocking of descending facilitation targeting μ opioid receptor positive neurons in the rostral ventromedial medulla ( RVM) in a rat model of bone cancer pain. Methods Forty-eight adult female Wistar rats weighing 180-200 g were randomly divided into 6 groups: group Ⅰ control ( n = 3) ;group Ⅱ bone cancer pain induced by intra-tibia inoculation of Walker 256 mammary gland carcinoma cells ( n = 9) ;group Ⅲ-Ⅵ received a single intra-RVM micro-injection of PBS (group Ⅲ), dermorphin (group Ⅳ) , saporin (group Ⅴ) and dermorphin-saporin ( group Ⅵ) respectively at 28 days before intra-tibia inoculation ( n = 9 each) . Starting from 3 to 20 days after intra-tibia inoculation, mechanical allodynia was assessed and recorded. The animals were sacrificed on 7, 14 and 20 days after intra-tibia inoculation, after repetitive non-noxious tactile stimulation of the hindpaw. The total number of Fos-positive neurons in the spinal dorsal horn was measured as a marker indicative of central sensitization. Results The animals developed nociceptive hypersensitivity after intra-tibia cancer cell inoculation in group Ⅱ -Ⅵ . Nociceptive hypersensitivity was significantly decreased during 4-7 days after the onset of nociception in group Ⅵ (dermorphin-saporin). The number of Fos positive neurons in bilateral spinal dorsal horn was significantly increased by intra-tibia inoculation of cancer cells in group Ⅱ-Ⅵ as compared with control group and was significantly lower at day 14 and 20 after inoculation in group Ⅵ (dermorphin-saporin) than in group Ⅱ - Ⅴ.Conclusion Selective blocking of descending facilitation targeting μ opioid receptor positive neurons in RVM can effectively reduce nociceptive hypersensitivity induced by intra-tibia inoculation of Walker56 mammary gland carcinoma cells.

Objective:To study effect of SC-LK on the immune function of immunosuppressive mice and to seek the relationship between drug property of SC-GS and immunoenhancement activity. Methods:The immunosuppressive mice models were established by CTX and administrated with four groups of drugs. The phagocytic ability of macrophage,serum hemolysin level,and proliferative response of T lymphocyte induced by PHA were measured. The activity of in vitro M? and the phagocytizing of CRBC by M? were measured. Results:SC-LK could significantly improve immunological function inhibited by CTX in mice. Conclusion:The improving of immunological function was a common effect in drug effect spectrum(drug property) of SC-LK,but it was not characteristic effect as compared with the other three groups of drugs.