AIM:To investigate the role of BRCA2 and CDKN1A interacting protein(BCCIP)in gastric can-cer(GC)and elucidate its mechanism in mediating cisplatin resistance.METHODS:The BCCIP mRNA expression was assessed in GC tissues(n=415)and normal tissues(n=34)using The Cancer Genome Atlas(TCGA)database.In an in-ternal cohort(n=36 for RT-qPCR;n=5 for Western blot;n=30 for immunohistochemistry),BCCIP expression at both mRNA and protein levels was examined in GC tissues and paired adjacent normal tissues.Human GC cell lines AGS and HGC27 were cultured in vitro and treated with cisplatin in a dose(0,2,4,6,8 and 10 μmol/L)-and time(0,6,24 and 48 h)-dependent manner,followed by Western blot analysis of BCCIP expression.Stable BCCIP knockdown cell lines(shRNA#1 and shRNA#2 groups)were generated via lentiviral transfection,with empty vector-transfected cells serving as controls(vector group).Flow cytometry and colony formation assay were performed to evaluate the effects of BCCIP on apoptosis and colony-forming ability of GC cells treated with cisplatin.Western blot was utilized to detect the changes of BCCIP protein expression levels in the cytoplasm and nucleus of GC cells after cisplatin(2.5 and 1.0 μmol/L)treatment,as well as the effects of BCCIP on the expression of DNA damage marker γ-H2AX and apoptosis-related proteins cleaved caspase-9 and cleaved caspase-3,and the activation of checkpoint kinase 1(CHK1)after cisplatin(2.5 and 1.0 μmol/L)treatment.Immunofluorescence was conducted to observe the effect of BCCIP on γ-H2AX expression in GC cells treated with cisplatin(2.5 and 1.0 μmol/L).RESULTS:The BCCIP expression was significantly up-regulated in GC tissues compared with normal tissues(P<0.01).Cisplatin induced up-regulation of BCCIP expression in a dose-and time-depen-dent manner.Knockdown of BCCIP significantly enhanced cisplatin-induced apoptosis(P<0.01)and reduced colony-forming ability(P<0.05)of GC cells.Knockdown of BCCIP promoted the expression of γ-H2AX,but inhibited the activa-tion of CHK1 after cisplatin treatment,with increased protein levels of cleaved caspase-9 and cleaved caspase-3(P<0.01).CONCLUSION:Cisplatin promotes the expression of BCCIP in GC cells.BCCIP confers cisplatin resistance in GC cells by suppressing apoptosis through modulation of DNA damage response pathways.

AIM:To investigate the role of BRCA2 and CDKN1A interacting protein(BCCIP)in gastric can-cer(GC)and elucidate its mechanism in mediating cisplatin resistance.METHODS:The BCCIP mRNA expression was assessed in GC tissues(n=415)and normal tissues(n=34)using The Cancer Genome Atlas(TCGA)database.In an in-ternal cohort(n=36 for RT-qPCR;n=5 for Western blot;n=30 for immunohistochemistry),BCCIP expression at both mRNA and protein levels was examined in GC tissues and paired adjacent normal tissues.Human GC cell lines AGS and HGC27 were cultured in vitro and treated with cisplatin in a dose(0,2,4,6,8 and 10 μmol/L)-and time(0,6,24 and 48 h)-dependent manner,followed by Western blot analysis of BCCIP expression.Stable BCCIP knockdown cell lines(shRNA#1 and shRNA#2 groups)were generated via lentiviral transfection,with empty vector-transfected cells serving as controls(vector group).Flow cytometry and colony formation assay were performed to evaluate the effects of BCCIP on apoptosis and colony-forming ability of GC cells treated with cisplatin.Western blot was utilized to detect the changes of BCCIP protein expression levels in the cytoplasm and nucleus of GC cells after cisplatin(2.5 and 1.0 μmol/L)treatment,as well as the effects of BCCIP on the expression of DNA damage marker γ-H2AX and apoptosis-related proteins cleaved caspase-9 and cleaved caspase-3,and the activation of checkpoint kinase 1(CHK1)after cisplatin(2.5 and 1.0 μmol/L)treatment.Immunofluorescence was conducted to observe the effect of BCCIP on γ-H2AX expression in GC cells treated with cisplatin(2.5 and 1.0 μmol/L).RESULTS:The BCCIP expression was significantly up-regulated in GC tissues compared with normal tissues(P<0.01).Cisplatin induced up-regulation of BCCIP expression in a dose-and time-depen-dent manner.Knockdown of BCCIP significantly enhanced cisplatin-induced apoptosis(P<0.01)and reduced colony-forming ability(P<0.05)of GC cells.Knockdown of BCCIP promoted the expression of γ-H2AX,but inhibited the activa-tion of CHK1 after cisplatin treatment,with increased protein levels of cleaved caspase-9 and cleaved caspase-3(P<0.01).CONCLUSION:Cisplatin promotes the expression of BCCIP in GC cells.BCCIP confers cisplatin resistance in GC cells by suppressing apoptosis through modulation of DNA damage response pathways.

Pyroptosis is a newly discovered kind of cell death modality that, due to its association with innate immunity, plays a crucial role in cytolysis and inflammatory cytokine release during host defense against infection. In recent years, studies have shown that pyroptosis plays an important role in the occurrence and development of liver diseases. This article introduces and elaborates on the most recent research progress on pyroptosis in liver diseases based on the morphological features, molecular and pathophysiological mechanisms.

ObjectiveTo construct a quantitative prediction model of three indicators（moisture absorption rate， film thickness and coating weight gain） during the coating process of Vitamin C Yinqiao tablets（VCYT） by near-infrared spectroscopy（NIRS）， and to realize the endpoint judgment. MethodReal-time NIRS data of 4 batches of VCYT during the coating process were collected by diffuse reflection method. The coating method employed was the rolling coating method， and the samples were obtained at the spray stage from the coater's sampling port every 10 minutes， and 57 batches of samples（about 1 800 tablets） were collected at various coating times， the tablets were embedded in molten paraffin， cut longitudinally， and observed by stereomicroscope. The film thickness， with a target value of 38 μm， was then measured using Motic Images Advanced 3.2 software. Furthermore， the mositure absorption rate of samples， aiming for a target value of 3%， was determined in accordance with guiding principles for drug hygroscopicity testing in the 2020 edition of Chinese Pharmacopoeia， and 3 samples were randomly selected from each batch（10 tablets per batch）， and the coating weight gain was calculated（target value of 4%）. Partial least squares regression（PLSR） was used to construct a quantitative model of the 3 coating indicators， and the predicted values of the coating indicators were smoothed using the moving average method and used to determine the coating endpoints. ResultThe prediction determination coefficients（R_p²） for moisture absorption rate， film thickness and coating weight gain were 0.933 4， 0.932 6 and 0.965 9， the root mean square errors of prediction（RMSEP） were 0.163 5%， 1.870 9 μm and 0.240 3%， the relative percent deviations（RPD） were 3.711 0， 2.760 7 and 5.415 8， respectively. The results of the external validation set demonstrated that the real-time predicted values obtained by the models exhibited the same trend as the measured values， and the coating endpoint could be accurately predicted（with a prediction error of less than 7.32 min and a relative error of less than 5.63%）. ConclusionThe established NIRS model exhibits excellent predictive performance and can be used for quality control of VCYT during the coating process.

Objective To explore the changes in serum energy metabolites in patients with peripheral T-cell lymphoma,and investigate serum biomarkers for monitoring peripheral T-cell lymphoma from the perspective of energy metabolism.Methods Multiple/selected reaction monitoring(MRM/SRM)was used to detect the energy-related metabolites in the sera of 16 patients with newly diagnosed peripheral T-cell lymphoma admitted in the Hematology Medical Center of the Second Affiliated Hospital of Army Medical University from November 2020 to December 2021,as well as 10 recruited healthy volunteers.The corresponding clinical data including medical history,laboratory results and image data were collected and retrospectively analyzed.Results Significant differences were seen in the contents and expression profiles of serum energy metabolism-related products between the patients and the healthy volunteers.The patients had significantly reduced serum contents of cyclic AMP,succinate,citrate and cis-aconitate(P＜0.05),and elevated D-glucose 6-phosphate content(P＜0.05).The serum contents of citrate and succinate were negatively correlated with the risk stratification(low-,moderate-and high-risk)and clinical stage of the disease(P＜0.05).Meanwhile,there was a negative correlation between the contents of L-malic acid and citrate and the mid-term efficacy evaluation results,such as complete/partial response(CR/PR)or stable disease(SD)(P＜0.05).For patients with extranodal NK/T cell lymphoma(n=10),there were also significant reductions in the contents of cyclic AMP,succinate,citrate,isocitrate and cis-aconitate in the sera of patients compared with healthy volunteers(P＜0.05),and the contents of citrate and succinate were negatively correlated with the clinical stage(P＜0.05)and were rather correlated with mid-term efficacy evaluation results(CR/PR or SD)(P＜0.05).For patients with angioimmunoblastic T-cell lymphoma(n=6),the serum contents of cyclic AMP,citrate and succinate were significantly lower,while the content of D-glucose 6-phosphate was higher when compared with the healthy volunteers(P＜0.05),and the content of succinate was negatively correlated with both clinical stage and risk grade of the patients(P＜0.05).Conclusion There are 5 serum differential metabolites identified between patients with peripheral T-cell lymphoma and healthy controls,and succinate and citrate are expected to be serum biomarkers of peripheral T-cell lymphoma.

BACKGROUND:Recently,regenerative endodontic therapy is a promising alternative to the maturation of tissue engineering.Inflammatory microenvironment plays a key role in regulating pulp regeneration. OBJECTIVE:To focus on the change in the inflammatory pulp microenvironment,the balance between inflammation and regeneration,and the research advances in tissue-engineered regenerative endodontic therapy within the context of the inflammatory microenvironment to provide a reference for future investigations into regenerative endodontic therapy. METHODS:We conducted a literature search on PubMed and CNKI using search terms"pulp regeneration,inflammation,regenerative endodontic therapy,tissue engineering"in Chinese and English for articles published between 2013 and 2023.The review finally included 61 relevant articles. RESULTS AND CONCLUSION:(1)The changes in the microenvironment of pulpitis involve a complex interplay of cellular and molecular reactions,which,as inflammation progresses,ultimately the microenvironment hinders tissue repair more than facilitates it.(2)Inflammation can promote dental pulp regeneration through stem cell recruitment and activate the complement system,but it can also hinder the regenerative process through immunosuppression and fibrosis.(3)Tissue engineering's three components(stem cells,growth factors,scaffold materials)collaborate to balance inflammation and regeneration,for example,by using interleukin-6 to regulate dental pulp stem cells and foster a regenerative environment.(4)Current research has been largely silent on infection and inflammation issues.The mechanisms underlying changes in the microenvironment of pulpitis are still not fully understood.One promising avenue for improving the clinical applicability of regenerative dental pulp therapy is to achieve precise regulation of the inflammatory-regeneration balance and create a regenerative microenvironment by synergistically leveraging the three elements of tissue engineering.However,this field of investigation still exhibits significant gaps in understanding,necessitating further exploration into innovative strategies for facilitating dental pulp regeneration under inflammation.As such,additional animal experimentation and randomized clinical trials are required to establish a robust foundation for the clinical practice of tissue engineering-based regenerative dental pulp therapy.

BACKGROUND:Prosthesis loosening and wear are still the main problems in the failure of total ankle replacement,which are closely related to the micro-motion of the implant-bone interface,the contact stress of the articular surface and joint motion.The design of artificial joint components,including insert and tibial/talar stem prosthesis,is a key factor affecting the force,motion,and micromotion of the contact interface of the ankle joint.The development of new inserts is of great significance to improve the survival rate of artificial ankle joints. OBJECTIVE:The finite element model of the total ankle replacement model was constructed to detect the biomechanical properties of the porous structure-optimized inserts,and the effect of the porous structure-optimized inserts on reducing prosthesis micromotion and improving the contact behavior of the articular surface was analyzed. METHODS:Based on the CT scan data of the right ankle joint of a healthy adult and the INBONE Ⅱ system product manual,a three-dimensional model including bone and artificial joint system was established,and the total ankle replacement model(model A)was obtained after osteotomy and prosthesis installation,and then through four new types of inserts,G50,G60,D50,and D60,were obtained by transforming the porous structure of the original insert,and the original one was replaced with different inserts to establish an optimized total ankle replacement model(models B-E)corresponding to the inserts.The gait loads were applied on the five models to simulate the gait conditions.The differences in micromotion and articular surface contact behaviors at the implant-bone interface of all five models were compared. RESULTS AND CONCLUSION:(1)In the gait cycle,the micromotion of the prosthesis of the four optimized total ankle replacement models was lower than that of the original model.Compared with model A,the micromotion of the prosthesis in models B-E decreased by 5.4%,10.1%,8.1%,and 20.9%,respectively.The high micromotion area of t ??he tibial groove dome in the optimized model was significantly smaller than that of the original model.(2)The four optimized models obtained a larger articular surface contact area.Compared with model A,the average contact area of t ??he inserts in models B-E increased by 11.8%,14.7%,8.1%,and 32.6%,respectively.(3)Similar to the effect of increasing the contact area,compared with the original model,the contact stress of the optimized model decreased in varying degrees,and the value of model E decreased the most significantly(P<0.05),it is due to good mechanical properties and large porosity of the Diamond lattice that constitutes the D60-type insert.(4)The research results show that the use of porous structure to improve the inserts can improve the elasticity of the inserts and increase its ability to absorb joint impact,for favorable conditions are created for reducing micromotion at the implant-bone interface and improving joint contact behavior.

Yellowish sweating disease is one of the fluid-retention diseases recorded in Jin Gui Yao Lve(Synopsis of the Golden Cabinet).The symptoms of yellowish sweating disease are complex,involving multiple visceral lesions,which are caused by interior heat and exterior deficiency,together with the concurrent invasion of pathogens of wind and water.Huangqi Shaoyao Guizhi Kujiu Decoction(mainly composed of Astragali Radix,Paeoniae Radix Alba,Cinnamomi Ramulus and vinegar)and Guizhi Plus Huangqi Decoction(mainly composed of Cinnamomi Ramulus and Astragali Radix)are the classical formula for the treatment of yellowish sweating disease.Both of the formulas have the actions of warming defensive qi and dredging yang,removing fluid retention and resolving dampness.Usually suffering heat in the spleen and stomach,together with carelessness in daily living and wind-water pathogens attacking the exterior,contributes to the key pathogenesis of diabetes mellitus.The clinical manifestations,etiology,occurrence and progression,and prognosis of yellowish sweating disease are similar to those of diabetic complications.Therefore,the treatment of diabetes complications such as diabetic kidney disease,diabetic cardiomyopathy,diabetic peripheral neuropathy,diabetes mellitus complicated with liver dysfunction,diabetic foot,and diabetic retinopathy can follow the therapeutic principles of yellowish sweating disease,and can be achieved by the therapies of clearing heat and purging fire,dispelling cold and removing dampness,and nourishing nutritive yin and harmonizing defensive qi with the appropriate formulas.The exploration of the treatment of diabetes mellitus and its complications from the pathogenesis and symptom characteristics of yellowish sweating disease will expand the thoughts for treating diabetic complications with traditional Chinese medicine.

OBJECTIVE: To discuss the influence of artificial ankle elastic improved inserts (hereinafter referred to as "improved inserts") in reducing prosthesis micromotion and improving joint surface contact mechanics by finite element analysis. METHODS: Based on the original insert of INBONE Ⅱ implant system (model A), four kinds of improved inserts were constructed by adding arc or platform type flexible layer with thickness of 1.3 or 2.6 mm, respectively. They were Flying goose type_1.3 elastic improved insert (model B), Flying goose type_2.6 elastic improved insert (model C), Platform type_1.3 elastic improved insert (model D), Platform type_2.6 elastic improved insert (model E). Then, the CT data of right ankle at neutral position of a healthy adult male volunteer was collected, and finite element models of total ankle replacement (TAR) was constructed based on model A-E prostheses by software of Mimics 19.0, Geomagic wrap 2017, Creo 6.0, Hypermesh 14.0, and Abaqus 6.14. Finally, the differences of bone-metal prosthesis interface micromotion and articular surface contact behavior between different models were investigated under ISO gait load. RESULTS: The tibia/talus-metal prosthesis interfaces micromotion of the five TAR models gradually increased during the support phase, then gradually fell back after entering the swing phase. The improved models (models B-E) showed lower bone-metal prosthesis interface micromotion when compared with the original model (model A), but there was no significant difference among models A-E ( P>0.05). The maximum micromotion of tibia appeared at the dome of the tibial bone groove, and the ​​micromotion area was the largest in model A and the smallest in model E. The maximum micromotion of talus appeared at the posterior surface of the central bone groove, and there was no difference in the micromotion area among models A-E. The contact area of the articular surface of the insert/talus prosthesis in each group increased in the support phase and decreased in the swing phase during the gait cycle. Compared with model A, the articular surface contact area of models B-E increased, but there was no significant difference among models A-E ( P>0.05). The change trend of the maximum stress on the articular surface of the inserts/talus prosthesis was similar to that of the contact area. Only the maximum contact stress of the insert joint surface of models D and E was lower than that of model A, while the maximum contact stress of the talar prosthesis joint surface of models B-E was lower than that of model A, but there was no significant difference among models A-E ( P>0.05). The high stress area of the lateral articular surface of the improved inserts significantly reduced, and the articular surface stress distribution of the talus prosthesis was more uniform. CONCLUSION Adding a flexible layer in the insert can improve the elasticity of the overall component, which is beneficial to absorb the impact force of the artificial ankle joint, thereby reducing interface micromotion and improving contact behavior. The mechanical properties of the inserts designed with the platform type and thicker flexible layer are better.
Adult ; Male ; Humans ; Ankle ; Ankle Joint/surgery* ; Finite Element Analysis ; Tibia/surgery* ; Talus ; Stress, Mechanical ; Biomechanical Phenomena

Aim To observe whether the mechanosensitive ion channel Piezo1 was involved in the senescence of atrial fibroblasts by activating β-catenin based on our previous study which found marked increase of Piezo1 mRNA in senescent atrial fibroblasts. Methods Primary mouse atrial fibroblasts (MAFs) were isolated from male C57BL/6 mice (3-4 weeks) by enzyme digestion, and tert-butyl hydroperoxide (TBHP) was used to induce the senescence of cells. The ratio of senescent cells was detected by senescence-associated β-galactosidase (SA-β-Gal) staining. The protein levels of Piezo1, β-catenin/p-β-catenin, senescence-associated proteins p53 and p21 in the cells treated with TBHP (100 μmol · L