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.

BACKGROUND: T cell dysfunction, which includes exhaustion, anergy, and senescence, is a distinct T cell differentiation state that occurs after antigen exposure. Although T cell dysfunction has been a cornerstone of cancer immunotherapy, its potential in transplant research, while not yet as extensively explored, is attracting growing interest. Interferon regulatory factor 4 (IRF4) has been shown to play a pivotal role in inducing T cell dysfunction. METHODS: A novel ultra-low-dose combination of Trametinib and Rapamycin, targeting IRF4 inhibition, was employed to investigate T cell proliferation, apoptosis, cytokine secretion, expression of T-cell dysfunction-associated molecules, effects of mitogen-activated protein kinase (MAPK) and mammalian target of rapamycin (mTOR) signaling pathways, and allograft survival in both in vitro and BALB/c to C57BL/6 mouse cardiac transplantation models. RESULTS: In vitro , blockade of IRF4 in T cells effectively inhibited T cell proliferation, increased apoptosis, and significantly upregulated the expression of programmed cell death protein 1 (PD-1), Helios, CD160, and cytotoxic T lymphocyte-associated antigen (CTLA-4), markers of T cell dysfunction. Furthermore, it suppressed the secretion of pro-inflammatory cytokines interferon (IFN)-γ and interleukin (IL)-17. Combining ultra-low-dose Trametinib (0.1 mg·kg -1 ·day -1 ) and Rapamycin (0.1 mg·kg -1 ·day -1 ) demonstrably extended graft survival, with 4 out of 5 mice exceeding 100 days post-transplantation. Moreover, analysis of grafts at day 7 confirmed sustained IFN regulatory factor 4 (IRF4) inhibition, enhanced PD-1 expression, and suppressed IFN-γ secretion, reinforcing the in vivo efficacy of this IRF4-targeting approach. The combination of Trametinib and Rapamycin synergistically inhibited the MAPK and mTOR signaling network, leading to a more pronounced suppression of IRF4 expression. CONCLUSIONS Targeting IRF4, a key regulator of T cell dysfunction, presents a promising avenue for inducing transplant immune tolerance. In this study, we demonstrate that a novel ultra-low-dose combination of Trametinib and Rapamycin synergistically suppresses the MAPK and mTOR signaling network, leading to profound IRF4 inhibition, promoting allograft acceptance, and offering a potential new therapeutic strategy for improved transplant outcomes. However, further research is necessary to elucidate the underlying pharmacological mechanisms and facilitate translation to clinical practice.
Animals ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Interferon Regulatory Factors/metabolism* ; Heart Transplantation/methods* ; T-Lymphocytes/immunology* ; Sirolimus/therapeutic use* ; Pyridones/therapeutic use* ; Graft Survival/drug effects* ; Pyrimidinones/therapeutic use* ; Cell Proliferation/drug effects* ; Apoptosis/drug effects* ; Male ; Signal Transduction/drug effects*

PURPOSE: Intertrochanteric fractures undergoing proximal femoral nail antirotation (PFNA) surgery are associated with significant hidden blood loss. This study aimed to explore whether intramedullary administration of tranexamic acid (TXA) can reduce bleeding in PFNA surgery for intertrochanteric fractures in elderly individuals. METHODS: A randomized controlled trial was conducted from January 2019 to December 2022. Patients aged over 60 years with intertrochanteric fractures who underwent intramedullary fixation surgery with PFNA were eligible for inclusion and grouped according to random numbers. A total of 249 patients were initially enrolled, of which 83 were randomly allocated to the TXA group and 82 were allocated to the saline group. The TXA group received intramedullary perfusion of TXA after the bone marrow was reamed. The primary outcomes were total peri-operative blood loss and post-operative transfusion rate. The occurrence of adverse events was also recorded. Continuous data was analyzed by unpaired t-test or Mann-Whitney U test, and categorical data was analyzed by Pearson Chi-square test. RESULTS: The total peri-operative blood loss (mL) in the TXA group was significantly lower than that in the saline group (577.23 ± 358.02 vs. 716.89 ± 420.30, p = 0.031). The post-operative transfusion rate was 30.67% in the TXA group and 47.95% in the saline group (p = 0.031). The extent of post-operative deep venous thrombosis and the 3-month mortality rate were similar between the 2 groups. CONCLUSION We observed that intramedullary administration of TXA in PFNA surgery for intertrochanteric fractures in elderly individuals resulted in less peri-operative blood loss and decreased transfusion rate, without any adverse effects, and is, thus, recommended.
Humans ; Tranexamic Acid/administration & dosage* ; Hip Fractures/surgery* ; Male ; Aged ; Female ; Fracture Fixation, Intramedullary/adverse effects* ; Blood Loss, Surgical/prevention & control* ; Antifibrinolytic Agents/administration & dosage* ; Aged, 80 and over ; Bone Nails ; Middle Aged ; Blood Transfusion/statistics & numerical data*

Objective To assess the clinical feasibility of a self-developed augmented reality(AR)system in surgeries for cerebral arteriovenous malformation(AVM),dural arteriovenous fistula(DAVF),moyamoya,and internal carotid artery stenosis.This system integrates preoperative vascular imaging(CTA,MRA,DSA)with intraoperative real-time visualization through high-precision patient-image registration and virtual-real integration technology.Methods A retrospective analysis was conducted on 6 patients(1 cerebral AVM,1 DAVF,3 moyamoya and 1 internal carotid artery stenosis)collected between March 2023 and April 2024.AR with three-dimensional reconstruction was used for preoperative precise localization and intraoperative navigation guidance.Clinical feasibility was evaluated and analyzed using an intraoperative self-controlled method.Results All 6 patients with diverse etiologies successfully underwent preoperative precise localization and intraoperative navigation guidance under AR three-dimensional reconstruction modeling.This technology achieved visualization of intracranial arteriovenous structures and precise lesion locations,providing surgeons with a visual reference for accurate planning of the surgical approach and operative field.Conclusion The application of AR with three-dimensional reconstruction is safe and feasible in neurosurgical procedures for cerebrovascular diseases.It demonstrates satisfactory effectiveness in preoperative localization and intraoperative navigation guidance.

BACKGROUND:Magnetic resonance imaging is the gold standard for the diagnosis of osteonecrosis of femoral head,and previous methods of predicting osteonecrosis of femoral head collapse based on magnetic resonance images mostly require the combined assessment of coronal and sagittal images.However,osteonecrosis of femoral head tends to occur bilaterally,most hospitals perform bilateral hip magnetic resonance imaging scans during clinical examinations,but the bilateral hip scans can only view coronal and cross-sectional images,and it is difficult to obtain sagittal images,which affects the assessment of the risk of collapse.Therefore,it is of clinical value to establish a method to assess the risk of early osteonecrosis of femoral head collapse by applying the images that can be obtained after bilateral hip magnetic resonance scanning. OBJECTIVE:To establish a method of applying coronal and cross-sectional images of bilateral hip magnetic resonance imaging to assess the risk of osteonecrosis of femoral head collapse. METHODS:The medical records of 111 patients(181 hips)with early-stage osteonecrosis of femoral head diagnosed at the outpatient clinic of Honghui Hospital Affiliated to Xi'an Jiaotong University from October 2017 to October 2019 were retrospectively analyzed.They were categorized into collapsed and non-collapsed groups according to the femoral head collapse at the final follow-up,with 69 hips in the collapsed group and 112 hips in the non-collapsed group.The angle of necrotic range on the images of median coronal plane,transverse plane or one level above and below it was measured on the magnetic resonance imaging system.The sum of the two angles of necrotic angle on the coronal and transverse planes was used as the combined necrotic angle.The average of the three combined necrotic angles of each hip was taken to get the average combined necrotic angle of each hip.Finally,the correlation between the three combined necrotic angles and the average combined necrotic angle with the collapse of osteonecrosis of femoral head was analyzed,and the specificity and sensitivity of the four combined necrotic angles in predicting collapse were evaluated by using receiver operating characteristic curves. RESULTS AND CONCLUSION:(1)Totally 69 hips(38.1%)had femoral head collapse at the last follow-up and were included in the collapsed group;112 hips(61.9%)did not have progression of collapse and were included in the non-collapsed group.(2)The difference between the collapsed group and the non-collapsed group in terms of Association Research Circulation Osseous(ARCO)stage was significant(P<0.001).The difference in age,body mass index,follow-up time,gender distribution,side of onset,and causative factors was not significant(P>0.05).(3)The results of independent samples t-test suggested that all four combined necrotic angles were significantly correlated with collapse(P<0.000 1);and the differences in combined necrotic angles between the collapsed group and the non-collapsed group of ARCO stage I and the two groups of ARCO stage II were all significant(P<0.000 1).(4)In the analysis of the receiver operating characteristic,the area under the curve of the average combined necrotic angle was greater than that of the combined necrotic angle on the lower level of the median,the middle level,and the upper level of the median.(5)The average combined necrotic angle had a higher accuracy in the prediction of collapse than the lower level of the median,the middle level,and the upper level of the combined necrotic angle.(6)It is concluded that the accuracy of the average combined necrotic angle in predicting the risk of osteonecrosis of femoral head collapse is higher,and the clinical practicability is stronger,so we can consider using this method to predict the risk of osteonecrosis of femoral head collapse.

AIM:To compare the changes in diopters and axial length after 1 a of wearing defocus incorporated multiple segments(DIMS)lenses or single vision(SV)spectacle lenses in children with monocular myopia.METHODS:In this retrospective case group study, monocular myopia children aged from 6 to 14 years old in Hankou Aier Eye Hospital from October 2020 to October 2022, who were fitted with DIMS lens(n=52)or single-vision(SV)spectacle lenses(n=49)were collected. The spherical degree of myopia eyes ranged from -4.00 D to -0.50 D and the nonmyopic eyes ranged from 0 to +1.00 D, astigmatism in all eyes ranged from 0 to -2.00 D. The DIMS lens group was classified into DIMS-myopia group(the myopic eyes)and DIMS-nonmyopia group(the nonmyopic eyes). The SV lens group was also divided into SV-myopia group and SV-nonmyopia group. The changes in spherical equivalent refraction(SER)and axial length(AL)of each group were compare before and after wearing lenses for 1 a, and variations in SER and AL of both eye among groups were analzed.RESULTS: After wearing lenses for 1 a, the changes of SER in the DIMS-myopic group and the DIMS-nonmyopic group were -0.41±0.44 and -0.26±0.54 D, respectively, and the changes of AL were 0.18±0.20 and 0.15±0.15 mm, respectively. SER changes were -0.74±0.63 and -0.70±0.68 D in SV-myopic group and SV-nonmyopic group, and AL changes were 0.30±0.28 and 0.31±0.28 mm. The changes of SER and AL in the DMS-myopic and non-myopic groups were slower than those in SV group(all P<0.05). Compared with SV lenses, wearing DIMS lenses delayed and 44.6% in myopia eyes, and 62.9% in non-myopia eyes, AL delayed by 40.0% in myopia eyes and 51.6% in non-myopia eyes. The percentage of 1-year AL change ≤0.2 mm in the DIMS-myopic group and non-myopic group was 53.9% and 65.4%, respectively, which was higher than that in the SV myopic group(34.7% and 42.9%, all P<0.05). The percentage of AL change >0.4 mm in the DIMS-myopic group and nonmyopic group was 17.3% and 7.7%, respectively, which was lower than that in the SV myopic group(32.7% and 28.6%, all P<0.05). There was no significant correlation between the change of AL and age and baseline AL in the DIMS-myopic and non-myopic groups after wearing lens for 1 a(all P>0.05); the change of AL in SV-myopic group and non-myopic group was negatively correlated with age(r=-0.446, P=0.001; r=-0.312, P=0.029), and there was no significant correlation with baseline AL(all P>0.05).CONCLUSION: DIMS lens has a good effect on myopia control and prevention in both myopia and non-myopia children with monocular myopia. Children with early pre-myopia can wear DIMS to prevent myopia.

[Objective]To evaluate the efficacy of ureteral dilation versus ureteral reimplantation in treating pediatric primary obstructive megaureter(POM).[Methods]A retrospective analysis was conducted on clinical data of 53 pediatric patients with POM treated in the Department of Urology,Anhui Provincial Children's Hospital from April 2019 to September 2023.The cohort included 37 boys and 16 girls with 5 bilateral and 48 unilateral cases.The age ranged from 1 to 157 months,with a median age of 17.00(5.50-48.00)months.Patients were assigned to 3 groups based on the management of the ureteral stricture segment:dilation group(18 cases,19 sides),Cohen group(20 cases,24 sides),and Lich-Gregoir group(15 cases,15 sides).The duration of the operations,postoperative hospital stays,postoperative indwelling catheters,postoperative D-J stents;changes in renal pelvis anteroposterior diameter and ureteral diameter;and postoperative complications were compared to evaluate the therapeutic effects.[Results]All 53 patients successfully underwent surgery.The dilation group showed significantly shorter operative time,postoperative hospital stay,and postoperative catheterization duration compared to the Cohen and Lich-Gregoir groups(P＜0.05).However,the postoperative D-J stent time was longer in the dilation group than in the other 2 groups(P＜0.05).Upon follow-ups for 6-12 months after stent removal,all groups demonstrated statistically significant reductions in renal pelvis anteroposterior diameter and ureteral diameter compared to preoperative values(P＜0.05).No significant differences were observed among the 3 groups in hydronephrosis resolution rates(P＞0.05).Additionally,the incidence of postoperative complications(urinary tract infection,vesicoureteral reflux,and reoperation for restenosis)did not differ significantly among the groups(P＞0.05).[Conclusions]Ureteral dilation demonstrated non-inferior short-term clinical efficacy compared to ureteral reimplantation in managing POM in pediatric patients.With reduced operative time,minimal invasiveness,and technical simplicity,ureteral dilation may be considered a preferential treatment option for children with POM.

OBJECTIVE T o explore the effectiveness and safety of azvudine in prevention of SARS-CoV-2 infection among the population of close contact with families with symptomatic SARS-CoV-2 infection.METHODS A total of 64 people who were closely contact with the families with symptomatic SARS-CoV-2 infection and were trea-ted in Ma'anshan People's Hospital from Jan.2023 to Oct.2023 were enrolled in the study and randomly divid-ed into the group A with 22 cases,the group B with 17 cases and the group C with 25 cases.The group A was giv-en 5mg of azvudine,the group B was given 3mg of azvudine plus 2mg of placebo,and the group C was given 5 mg of azvudine;all the three groups were treated for 7 days in total.The incidence of SARS-CoV-2 infection and the levels of interleukin-6(IL-6),C-reactive protein(CRP),immunoglobulin G(IgG)and immunoglobulin M(IgM)were observed among the three groups of research subjects after the drug therapies;the adverse reactions were re-corded during the research period.RESULTS The incidence rate of SARS-CoV-2 infection was 4.55％in the group A,11.76％in the group B,12.00％in the group C,and there was no significant difference(x2=0.921,P=0.631).There were no significant differences in the levels of IL-6,CRP,IgG and IgM among the three groups be-fore and after the drug therapies.The incidence of adverse reactions such as fatigue,cough,hypertriglyceridemia and gastrointestinal tract reactions was 9.09％in the group A after the drug therapies,11.76％in the group B,12.00％in the group C,and there was no significant difference.CONCLUSION There is no significant difference in the effectiveness of azvudine in prevention of SARS-CoV-2 infection among the population of close contact with families with symptomatic SARS-CoV-2 infection,with the safety and tolerance favorable.

Objective:To investigate the effects of surgical timing on incidence of perioperative complications and postoperative 30-day mortality in elderly patients with hip fracture.Methods:The data were retrospectively analyzed of the 450 elderly patients with hip fracture who had been admitted to Department of Joint Surgery, Beijing Shijitan Hospital, Capital Medical University from January 2016 to December 2021. The patients were divided into 2 groups according to the time from admission to surgery. In the early surgery group of 143 cases [41 males and 102 females with an age of 82(75, 86) years], the time from admission to surgery was ≤ 48 hours. In the delayed surgery group of 307 cases [88 males and 219 females with an age of 83(77, 87) years], the time from admission to surgery was over 48 hours. The 2 groups were compared in terms of comorbidities, perioperative complications, death events within postoperative 30 days, ICU transfer rate and total length of hospital stay.Results:There was no significant difference in the preoperative general data like age and gender between the 2 groups, indicating comparability ( P>0.05). The proportions of patients with coronary atherosclerotic heart disease [30.0%(92/307)], a stroke history [19.9%(61/307)], abnormal heart function [55.4%(170/307)] and abnormal kidney function [24.4%(75/307)] in the delayed surgery group were significantly higher than those in the early surgery group [18.2%(26/143), 10.5% (15/143), 39.2%(56/143), and 12.6%(18/143)] ( P<0.05). The proportions of perioperative pulmonary infection [22.5% (69/307)] and urinary infection [21.2%(65/307)] in the delayed operation group were significantly higher than those in the early operation group [11.9%(17/143) and 11.2%(16/143)] ( P<0.05). The total hospital stay in the delayed operation group [18(14, 22) d] was significantly longer than that in the early operation group [14(10, 17) d] ( P<0.05). There was no significant difference in ICU transfer rate or postoperative 30-day mortality between the 2 groups ( P>0.05). Conclusion:For elderly patients with hip fracture, delayed surgery may increase the incidence of pulmonary infection and urinary infection, and extend their total hospital stay, but have no effect on the postoperative 30-day mortality.

Lung transplantation is a key therapeutic approach for patients with end-stage lung diseases. Although its clinical outcomes have significantly improved, multidimensional injuries sustained by donor lungs during procurement, preservation, and transplantation remain major challenges affecting graft survival and long-term prognosis. This article proposes the "Guangzhou Classification" for full-course management of donor lung injury, characterized by spatiotemporal dynamics. Based on the progression of disease stages, donor lung injuries are systematically divided into three types: primary injuries (including donor ICU-related lung injury, pathogen colonization, and cold ischemia injury), secondary injuries (such as ventilator-induced lung injury after transplantation, ischemia-reperfusion inflammatory storm, and early rejection), and accompanying injuries (organ toxicity caused by accumulation of postoperative sedatives, analgesics, and vasoactive drugs). Drawing on previous studies and the clinical experience of our center, this paper elaborates the temporal evolution, key risk factors, and prevention and treatment strategies of each injury category, and discusses future research directions. By targeting critical injury factors at each stage, this classification aims to optimize both short-term and long-term outcomes of lung transplantation.