ObjectiveTo verify the efficacy and safety of conversion from cyclosporine (CsA) to tacrolimus (Tac) in renal transplant recipients. MethodsThe clinical data of conversion from CsA to Tac in renal transplant recipients were retrospectively analyzed. In 97 patients undergoing kidney transplantation, there were 62 cases of chronic allograft nephropathy (CAN), 21 cases of refractory renal allograft rejection, 8 cases of hepatic impairment, and 6 cases of gingival overgrowth and hirsutism. The patients were followed up with renal function, hepatic function, blood fat, pressure,glucose,acute rejection incidence, patients/kidney survival rate,and adverse drug reaction for 3 years.ResultsThe renal function of patients with CAN and refractory acute rejection was greatly improved after conversion from CsA to Tac treatment at the first year (P＜0. 05) ,and steady at the 2nd or 3rd year. The conversion treatment could greatly improve the hepatic function of patients with dysfunction of liver, improve the gum hypertrophy and hypertrichosis results from CsA. The 1- and 3-year patients/kidney survival rate after conversion from CsA to Tac was 100 ％/97. 9 ％ and 100 ％/92. 8 ％, respectively. The conversion treatment showed a significantly lower degree of plasma cholesterol, low density lipoprotein, triglyceride, and blood pressure (P ＜ 0.05). Incidence of pathoglycemia, diarrhea or anepithymia,and tremor after conversion treatment was 13.4 ％ (13/97),2. 1％ (2/97) and 5. 2 ％ (5/97),respectively. There were no serious pulmonary infection and tumor during the observation period. ConclusionThe mid-long term effect of conversion from CsA to Tac in patients with kidney transplantation is safe and effective.

Precise orchestration of cell fate determination underlies the success of scaffold-based skeletal regeneration.Despite extensive studies on mineralized parenchymal tissue rebuilding,regenerating and maintaining undifferentiated mesenchyme within calvarial bone remain very challenging with limited advances yet.Current knowledge has evidenced the indispensability of rebuilding suture mesenchymal stem cell niches to avoid severe brain or even systematic damage.But to date,the absence of promising therapeutic biomaterials/scaffolds remains.The reason lies in the shortage of fundamental knowledge and methodological evidence to understand the cellular fate regulations of scaffolds.To address these issues,in this study,we systematically investigated the cellular fate determinations and transcriptomic mechanisms by distinct types of commonly used calvarial scaffolds.Our data elucidated the natural processes without scaffold transplantation and demonstrated how different scaffolds altered in vivo cellular responses.A feasible scaffold,polylactic acid electrospinning membrane(PLA),was next identified to precisely control mesenchymal ingrowth and self-renewal to rebuild non-osteogenic suture-like tissue at the defect center,meanwhile supporting proper osteointegration with defect bony edges.Especially,transcriptome analysis and cellular mechanisms underlying the well-orchestrated cell fate determination of PLA were deciphered.This study for the first time cellularly decoded the fate regulations of scaffolds in suture-bony composite defect healing,offering clinicians potential choices for regenerating such complicated injuries.

Objective:To explore the clinical characteristics, diagnosis and treatment of cryptococcal infection after renal transplantation.Methods:The clinical data were analyzed retrospectively for 17 hospitalized cases of cryptococcal infection after kidney transplantation from January 2003 to December 2019. The relevant parameters included site of infection, clinical manifestations, complications, comorbidities, treatments and outcomes. The average time to infection after transplantation was (7.9±5.4) years, the median baseline level of creatinine was 137(75-741) μmol/L. Concurrent conditions included hypertension (n=15, 88.2%), diabetes (n=6, 35.3%) and chronic hepatitis (n=9, 52.9%). The most common site of infection was central nervous system (88.2%), followed by lungs (29.4%) and skin (17.6%).Results:The clinical manifestations were diverse. Most patients received amphotericin B liposome and/or fluconazole as an initial option. The outcomes were curing (n=17, 58.8%), death from cryptococcal infection (n=5, 29.4%), partial relief (n=1, 5.9%) and stable disease (n=1, 5.9%). Among 10 curative cases, 2 cases died from other causes and 4 cases returned to hemodialysis with graft loss.Conclusions:Cryptococcosis is typically a late-occurring infection in kidney transplant recipients. Many factors, such as complications, nonstandard antifungal treatment, immune dysbalance, have adverse prognoses. Strengthening follow-ups, dealing with complications, validating the diagnosis early, interdepartmental cooperations, standardizing antifungal therapy and balancing immune status may improve the outcomes of cryptococcosis after kidney transplantation.

Objective:To explore the clinical characteristics and risk factors of pediatric kidney transplantation (KT).Methods:From January 1, 2010 to September 30, 2022, retrospective analysis was performed for the relevant clinical data of 81 pediatric recipients of primary KT at Organ Transplant Center of Shanghai Changzheng Hospital. The occurrences of acute rejection (AR) ,delayed graft function (DGF), infection, myelosuppression, tumor and other complications were observed within 1 year post-KT. They were grouped according to whether or not AR/DGF occurred. Univariate analysis speculated the effect of AR and DGF on renal function at 1 year after transplantation. Binary Logistic regression was employed for examining the risk factors related to AR/DGF.Results:During follow-ups, transplanted kidney was removed due to an embolization of renal vessels and dialysis resumed (n= 5). One child had failed graft due to the recurrence of original disease and dialysis resumed. The remaining 75 children had an excellent recovery of graft function. At the end of follow-ups, survival for transplant recipients and transplanted kidneys was 100% (81/81 ) and 92.6% (75/81) respectively. 23 patients (28.4%) developed DGF, including 20 child recipients of C-I donors. Among DGF recipients, 21 (91.3%) were immune induced with anti-CD25 humanized monoclonal antibody and 2 (8.7 %) with porcine antihuman lymphocyte immunoglobulin (pALG). Within the first year post-KT, 13 patients (16.1%) developed AR, including 11 child recipients of C-I donors. Induction was made with anti-CD25 humanized monoclonal antibody (n=8), pALG (n=4) and anti-human T lymphocyte rabbit immunoglobulin (n=1). And 12 cases were reversed with MP (methylprednisolone) shock therapy while another ineffective case was rescued by an intravenous infusion of rATG (rabbit anti-human thymocyte immunoglobulin). During postoperative follow-ups, 14 (17.3 %) KT recipients had an onset of pulmonary infection (n=7), upper respiratory tract infection (n=3), urinary tract infection (n=5), gastrointestinal infection (n=2) and abdominal cavity infection (n=1). The causative pathogens were bacteria (n=14) and viruses (n=4). Among 7 cases (8.6%) of myelosuppression, there were leukopenia (n=6) and thrombocytopenia (n=1 ). During 1-year follow-ups, no malignancy occurred. At the last follow-up, blood creatinine was (72.79±21.07) μmol/L in non-AR/DGF recipients. For AR/DGF recipients, blood creatinine levels were (68.83±10.78) and (74.20±18.70) μmol/L. There was no significant inter-group difference ( F=0.14, P=0.87). In groups with and without DGF, the incidence of bone marrow suppression in the children with DGF was significantly higher (21. 74 %) than that in the untreated group (3.45%), with a statistically significant difference ( P=0.02). However, there was no statistically significant difference in the age, sex, donor source, infection, and types of immune-induced drugs in AR, DGF occurrence and no occurrence group. logistic Regression analysis showed that immunoinduction therapy with lymphocyte inhibitor ( OR=0.074, 95 %CI: 0.009-0.0643, P=0.018) and bone marrow suppression ( OR=0.045, 95%CI: 0.004-0.515, P=0.013) were risk factors for DGF. Conclusion:KT in children may obtain decent outcomes. Immunoinduction therapy with lymphocyte inhibitors and occurrence of myelosuppression are risk factors for postoperative DGF. The occurrence of AR/DGF in early postoperative period does not affect the level of kidney function in children at 1 year post-KT. It is recommended to closely follow up and accumulate experiences for optimizing long-term outcomes.

Oxidative stress is closely associated with the development of oral diseases such as caries, periodontitis and endodontitis. The accompanying oxidative stress during inflammation could aggravate tissue damage. However, numerous studies have shown that some dental materials, such as composite resins, bleach, drugs for root canal irrigation and dental implants, can give rise to abundant free radicals, which have adverse effects on peripheral tissues. Therefore, it is essential to supplement with extra antioxidants against free radicals. Plant-derived natural antioxidants have attracted great attention in biomedicine because of their excellent biocompatibility and easy access. This paper focused on the redox imbalance in the oral cavity and the application of natural antioxidants to oral therapy and their modification of dental materials. Current research shows that by constructing polyphenol-based metal organic nanoenzymes or adding vitamins and polyphenols to bionic hydrogels, the safety and utilization rate of antioxidants can be significantly improved. However, these polymer delivery systems have problems such as poor degradability, hepatotoxicity and nephrotoxicity, and the research is still in its infancy. In terms of material modification, it is crucial to choose the type and ratio of natural antioxidants and raw materials, as well as appropriate modification methods. A strong chemical bond between the antioxidant and the raw material may lead to the failure of antioxidant release from the modified composite, lowering the antioxidant activity. At the same time, the selection of polyphenols rich in pyrogallol functional groups can retain more free phenolic hydroxyl groups after chemical modification, which is conducive to greater antioxidant activity by the implant materials. Although research on natural antioxidants in oral therapy has made progress, there is a lack of data supporting clinical trials and long-term application effects, and further research is still needed.

Histone acetylation and methylation can affect chromatin conformation and regulate a variety of biological activities.Abnormal histone acetylation and methylation modifications are related to the occurrence and development of a variety of oral diseases.Histone acetylation and methylation increase or decrease in an orderly manner to regulate the development of teeth.Fluoride ions can destroy the balance between histone acetylation and methylation,which may be related to the occurrence of dental fluorosis.In addition,histone acetylation and methylation are involved in the regula-tion of oral inflammatory diseases.In the inflammatory microenvironment,the expression of histone acetyltransferase GCN5 decreases,and the expression of Dickkopf 1(DKK1)decreases,activating the Wnt/β-catenin pathway and ulti-mately inhibiting the osteogenic differentiation of periodontal ligament stem cells.Enhancer of zeste homolog 2(EZH2)and H3K27me3 levels were decreased in inflamed dental pulp tissues and cells.EZH2 inhibition inhibited the expres-sion of interleukin(IL)-1b,IL-6 and IL-8 in human dental pulp cells under inflammatory stimulation.Histone acetyla-tion/methylation modifications can interact with multiple signaling pathways to promote the occurrence and development of oral tumors and are related to the high invasiveness of salivary gland tumors.Small molecule drugs targeting histone acetylation and methylation-related enzymes can regulate the level of histone methylation/acetylation and have shown po-tential in the treatment of oral and maxillofacial diseases.For example,the histone deacetylase inhibitor vorinostat can inhibit the secretion of inflammation-related cytokines;it also promotes the maturation of odontoblasts and the formation of dentin-related matrix,demonstrating its potential in pulp preservation.Understanding the role of histone acetylation/methylation modifications in the occurrence and development of oral diseases will help promote research on epigenetic modifications in oral diseases and provide new perspectives for disease diagnosis and treatment.

Inflammation-associated proteinase functions are key determinants of inflammatory stromal tissues deconstruction. As a specialized inflammatory pathological process, dental internal resorption (IR) includes both soft and hard tissues deconstruction within the dentin-pulp complex, which has been one of the main reasons for inflammatory tooth loss. Mechanisms of inflammatory matrix degradation and tissue resorption in IR are largely unclear. In this study, we used a combination of Cre-loxP reporter, flow cytometry, cell transplantation, and enzyme activities assay to mechanistically investigate the role of regenerative cells, odontoblasts (ODs), in inflammatory mineral resorption and matrices degradation. We report that inflamed ODs have strong capabilities of matrix degradation and tissue resorption. Traditionally, ODs are regarded as hard-tissue regenerative cells; however, our data unexpectedly present ODs as a crucial population that participates in IR-associated tissue deconstruction. Specifically, we uncovered that nuclear factor-kappa b (NF-κB) signaling orchestrated Tumor necrosis factor α (TNF-α)-induced matrix metalloproteinases (Mmps) and Cathepsin K (Ctsk) functions in ODs to enhance matrix degradation and tissue resorption. Furthermore, TNF-α increases Rankl/Opg ratio in ODs via NF-κB signaling by impairing Opg expression but increasing Rankl level, which utterly makes ODs cell line 17IIA11 (A11) become Trap⁺ and Ctsk⁺ multinucleated cells to perform resorptive actions. Blocking of NF-κB signaling significantly rescues matrix degradation and resorptive functions of inflamed ODs via repressing vital inflammatory proteinases Mmps and Ctsk. Utterly, via utilizing NF-κB specific small molecule inhibitors we satisfactorily attenuated inflammatory ODs-associated human dental IR in vivo. Our data reveal the underlying mechanisms of inflammatory matrix degradation and resorption via proteinase activities in IR-related pathological conditions.
Humans ; Matrix Metalloproteinases/metabolism* ; Minerals/metabolism* ; NF-kappa B/metabolism* ; Odontoblasts/metabolism* ; Osteoclasts/metabolism* ; RANK Ligand/metabolism* ; Tumor Necrosis Factor-alpha/metabolism*

Objective: To compare the color stability of Biodentine and mineral trioxide aggregate (MTA) within the blood environment in vitro and to further investigate the underlying reasons for such color instability. Methods : We first generated Biodentine and MTA discs with a diameter of 5 mm and a height of 3 mm. 24 discs of each material were randomly divided into two groups: the deionized water group and the defibrinated sheep blood group. Discs of each group were immersed for 1 day or 7 days before assessments. First, all discs were photographed to directly compare the discoloration of Biodentine and MTA. The color degree of the two materials was tested by a spectrophotometer. Then, the high-resolution morphological characteristics were observed by scanning electron microscopy. Finally, the chemical contents of each element in the material were measured by energy-dispersive spectroscopy. Results : Compared to immediately after stripping, a change in the brightness of discs after immersion in defibrinated sheep blood for 1 day was observed only in MTA. On the 7th day after being immersed in blood, the colors of both the Biodentine and MTA discs darkened and turned deep red, but the darkness of the MTA discs increased significantly. The color change of MTA immersed in blood was measured on a spectrophotometer with a greater 7-day ∆E (21.257 ± 0.955) than the Biodentine 7-day ∆E (5.833 ± 0.501) (t=24.781, P < 0.001). MTA exhibits more discoloration as the immersion time goes on. A significant difference was noted between the 1-day ∆E(6.233 ± 0.888) and the 7-day ∆E(t=19.956, P < 0.001) of MTA immersed in blood. However, there was no statistically significant difference between the 1-day ∆E (6.790 ± 0.831) and the 7-day ∆E(t=1.707, P=0.163) of Biodentine immersed in blood. It was observed by scanning electron microscopy that after 7 days of immersion in the defibrinated sheep ablood, the surface porosity of MTA was larger than that of Biodentine, and the crystal edge of MTA became rounded and blunt. The analysis by energy-dispersive X-ray spectroscopy showed that the oxygen content decreased and the bismuth content increased in MTA after immersion in defibrinated sheep blood for 7 days. Zirconium was not detected in Biodentine due to its low radiodensity, but the contents of other elements were stable in Biodentine after immersion in defibrinated sheep blood for 7 days. Conclusion The color stability of Biodentine within the blood environment is better than that of MTA in vitro, which is mainly related to the low surface porosity and stable composition of the anti-radiation agent of Biodentine.