BACKGROUND: Neoadjuvant chemoradiotherapy followed by radical surgery has been a common practice for patients with locally advanced rectal cancer, but the response rate varies among patients. This study aimed to develop a ResNet-Vision Transformer based magnetic resonance imaging (MRI)-endoscopy fusion model to precisely predict treatment response and provide personalized treatment. METHODS: In this multicenter study, 366 eligible patients who had undergone neoadjuvant chemoradiotherapy followed by radical surgery at eight Chinese tertiary hospitals between January 2017 and June 2024 were recruited, with 2928 pretreatment colonic endoscopic images and 366 pelvic MRI images. An MRI-endoscopy fusion model was constructed based on the ResNet backbone and Transformer network using pretreatment MRI and endoscopic images. Treatment response was defined as good response or non-good response based on the tumor regression grade. The Delong test and the Hanley-McNeil test were utilized to compare prediction performance among different models and different subgroups, respectively. The predictive performance of the MRI-endoscopy fusion model was comprehensively validated in the test sets and was further compared to that of the single-modal MRI model and single-modal endoscopy model. RESULTS: The MRI-endoscopy fusion model demonstrated favorable prediction performance. In the internal validation set, the area under the curve (AUC) and accuracy were 0.852 (95% confidence interval [CI]: 0.744-0.940) and 0.737 (95% CI: 0.712-0.844), respectively. Moreover, the AUC and accuracy reached 0.769 (95% CI: 0.678-0.861) and 0.729 (95% CI: 0.628-0.821), respectively, in the external test set. In addition, the MRI-endoscopy fusion model outperformed the single-modal MRI model (AUC: 0.692 [95% CI: 0.609-0.783], accuracy: 0.659 [95% CI: 0.565-0.775]) and the single-modal endoscopy model (AUC: 0.720 [95% CI: 0.617-0.823], accuracy: 0.713 [95% CI: 0.612-0.809]) in the external test set. CONCLUSION The MRI-endoscopy fusion model based on ResNet-Vision Transformer achieved favorable performance in predicting treatment response to neoadjuvant chemoradiotherapy and holds tremendous potential for enabling personalized treatment regimens for locally advanced rectal cancer patients.
Humans ; Rectal Neoplasms/diagnostic imaging* ; Magnetic Resonance Imaging/methods* ; Male ; Female ; Middle Aged ; Neoadjuvant Therapy/methods* ; Aged ; Adult ; Chemoradiotherapy/methods* ; Endoscopy/methods* ; Treatment Outcome

OBJECTIVE: To investigate the accuracy and safety of pedicle screw placement using 3D-printed auxiliary guides in scoliosis correction surgery for adolescents. METHODS: A retrospective analysis was conducted on the clinical data of 51 patients who underwent posterior scoliosis correction surgery from January 2020 to March 2023. Among them, there were 35 cases of adolescent idiopathic scoliosis and 16 cases of congenital scoliosis. The patients were divided into two groups based on the auxiliary tool used:the 3D-printed auxiliary guide screw placement group (3D printing group) and the free-hand screw placement group (free-hand group, without auxiliary tools). The 3D printing group included 32 patients (12 males and 20 females) with an average age of (12.59±2.60) years;the free-hand group included 19 patients (7 males and 12 females) with an average age of (14.58±3.53) years. The two groups were compared in terms of screw placement accuracy and safety, spinal correction rate, intraoperative blood loss, number of intraoperative fluoroscopies, operation time, hospital stay, and preoperative and last follow-up scores of the Scoliosis Research Society-22 (SRS-22) questionnaire. RESULTS: A total of 707 pedicle screws were placed in the two groups, with 441 screws in the 3D printing group and 266 screws in the free-hand group. All patients in both groups successfully completed the surgery. There was a statistically significant difference in operation time between the two groups (P<0.05). The screw placement accuracy rate of the 3D printing group was 95.46% (421/441), among which the Grade A placement rate was 89.34% (394/441);the screw placement accuracy rate of the free-hand group was 86.47% (230/266), with a Grade A placement rate of 73.31% (195/266). There were statistically significant differences in the accuracy of Grade A, B, and C screw placements between the two groups (P<0.05), while no statistically significant differences were observed in intraoperative blood loss, number of fluoroscopies, correction rate, or hospital stay (P>0.05). In the SRS-22 questionnaire scores, the scores of functional status and activity ability, self-image, mental status, and pain of patients in each group at the last follow-up were significantly improved compared with those before surgery (P<0.05), but there were no statistically significant differences in all scores between the two groups (P>0.05). CONCLUSION In scoliosis correction surgery, compared with traditional free-hand screw placement, the use of 3D-printed auxiliary guides for screw placement significantly improves the accuracy and safety of screw placement and shortens the operation time.
Humans ; Male ; Scoliosis/surgery* ; Female ; Adolescent ; Printing, Three-Dimensional ; Retrospective Studies ; Pedicle Screws ; Child

OBJECTIVES: To investigate the clinical characteristics and prognosis of chronic disseminated candidiasis (CDC) in children with acute leukemia (AL) following chemotherapy. METHODS: A retrospective analysis was conducted on children diagnosed with CDC (including confirmed, clinically diagnosed, and suspected cases) after AL chemotherapy from January 2015 to December 2023 at Fujian Medical University Union Hospital, Zhangzhou Municipal Hospital, and Quanzhou First Hospital Affiliated to Fujian Medical University. Clinical characteristics and prognosis were analyzed. RESULTS: The incidence of CDC in children with AL following chemotherapy was 1.92% (32/1 668). Among the children with acute lymphoblastic leukemia, the incidence of CDC in the high-risk group was significantly higher than in the low-risk group (P=0.002). All patients presented with fever unresponsive to antibiotics during the neutropenic period, with 81% (26/32) involving the liver. C-reactive protein (CRP) levels were significantly elevated (≥50 mg/L) in 97% (31/32) of the patients. The efficacy of combined therapy with liposomal amphotericin B and caspofungin or posaconazole for CDC was 66% (19/29), higher than with caspofungin (9%, 2/22) or liposomal amphotericin B (18%, 2/11) monotherapy. The overall cure rate was 72% (23/32). The proportion of patients with CRP ≥50 mg/L and/or a positive β-D-glucan test for more than 2 weeks and breakthrough infections during caspofungin treatment was significantly higher in the treatment failure group compared to the successful treatment group (P<0.05). CONCLUSIONS CDC in children with AL after chemotherapy may be associated with prolonged neutropenia due to intensive chemotherapy. Combination antifungal regimens based on liposomal amphotericin B have a higher cure rate, while persistently high CRP levels and positive β-D-glucan tests may indicate poor prognosis.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Antifungal Agents/therapeutic use* ; Candidiasis/diagnosis* ; Chronic Disease ; Leukemia/complications* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications* ; Prognosis ; Retrospective Studies

OBJECTIVE: To investigate the efficacy and safety of the conditioning regimen BeEAM (bendamustine+et-oposide+cytarabine+melphalan) in autologous stem cell transplantation (ASCT) for patients with malignant lymphoma. METHODS: The clinical data of 20 patients with malignant lymphoma who underwent ASCT after conditioning with BeEAM regimen from January 2021 to December 2022 in the First Affiliated Hospital of Bengbu Medical University were collected, and the clinical characteristics before transplantation, conditioning-related toxicity, hematopoietic reconstitution after transplantation, and therapeutic effects were analyzed. 67 patients with malignant lymphoma who did not undergo ASCT during the same period were selected as the control group, and the 1-year progression-free survival (PFS) rate and overall-survival (OS) rate between the ASCT group and the non-ASCT group were compared. RESULTS: 15 cases achieved complete remission (CR) and 5 cases achieved partial remission (PR) before transplantation in ASCT group. During the conditioning process of patients in the ASCT group, 14 cases experienced gastrointestinal adverse reactions, 13 cases experienced neutropenic fever, 10 cases experienced oral mucositis, 2 cases experienced abnormal liver function, and only 1 case experienced acute renal injury. All the adverse reactions resolved after symptomatic treatment. After transplantation, 19 cases achieved hematopoietic reconstitution, and only one case had poor platelet engraftment. The median time of peripheral white blood cell (WBC) engraftment was 9 (9-16) days, and the median time of platelet engraftment was 12 (10-23) days. By the end of follow-up, there were no transplant-related deaths. The 1-year PFS rates in the ASCT group and the non-ASCT group were 94.4% and 68.5%, respectively; The 1-year OS rates were 94.4% and 83.5%, respectively. The median PFS and OS time for both groups were not reached. The PFS in the ASCT group was significantly better than that in the non-ASCT group (P < 0.05), and there was no significant difference in OS between the two groups ( P >0.05). CONCLUSION BeEAM regimen is safe and effective as a conditioning treatment for ASCT in patients with malignant lymphoma, with tolerable adverse reactions, controllable non-hematological toxicity, smooth hematopoietic reconstitution, and considerable short-term efficacy. However, further follow-up is required to evaluate its long-term efficacy.
Humans ; Transplantation Conditioning/methods* ; Transplantation, Autologous ; Hematopoietic Stem Cell Transplantation ; Lymphoma/therapy* ; Cytarabine/therapeutic use* ; Female ; Male ; Melphalan/therapeutic use* ; Adult ; Middle Aged ; Bendamustine Hydrochloride/therapeutic use*

Objective To investigate the effect of cinobufacini on immune escape of acute myeloid leukemia(AML)by regulating myosin heavy chain 9(MYH9)/ubiquitin-specific protease 7(USP7)/cellular-myelocytomatosis viral oncogene(c-MYC)pathway.Methods(1)In vivo experiment:a nude mouse xenograft tumor model was established to evaluate the effect of cinobufotalin on the growth and immune escape of AML cells in vivo.(2)In vitro experiments:human AML cell line HL-60 was treated with different concentrations of cinobufacini,cell viability was detected by cell counting kit 8(CCK-8),and HL-60 cell invasion was detected by Transwell assay.HL-60 cells were co-cultured with activated CD8+ T cells,the expression of CD25,the surface marker of CD8+ T cells,was detected by flow cytometry,the levels of cytokines[interleukin-2(IL-2)and interferon(IFN-γ)]in the co-culture supernatant were detected by enzyme-linked immunosorbent assay(ELISA).CytoTox96 non-radioactive cytotoxicity assay was used to evaluate the cytotoxicity of CD8+ T cells to HL-60 cells.The protein expressions of MYH9,USP7 and c-MYC in HL-60 cells were detected by Western Blot.The interaction between MYH9,USP7 and ubiquitination was detected by co-immunoprecipitation(Co-IP)assay.The MYH9 overexpression plasmid was tranfected to verify the mechanism of cinobufacini in AML.Results Cinobufacini treatment inhibited xerograft tumor growth in nude mice and enhanced the anti-tumor ability of CD8+ T cells.Cinobufacini treatment inhibited HL-60 cell viability and invasion in a concentration-dependent manner.Cinobufacini treatment up-regulated the expression of CD25,a surface marker of CD8+ T cells,and also up-regulated the levels of IL-2 and IFN-γ.Cinobufotalin enhanced the toxicity of CD8+ T cells to HL-60 cells.Cinobufacini inhibits the protein expressions of MYH9,USP7 and c-MYC in HL-60 cells.MYH9 promotes c-MYC deubiquitination by recruiting USP7,but cinobufacini inhibits MYH9-mediated c-MYC deubiquitination.Conclusion Cinobufacini can reduce the recruitment of c-MYC by deubiquitinating enzyme USP7 by inhibiting the expression of MYH9,and promote the ubiquitination and degradation of c-MYC,thereby inhibiting the immune escape of AML cells.

Objective To investigate the clinical features and prognosis of children with fungal bloodstream infection(BSI)following chemotherapy for acute leukemia(AL).Methods A retrospective analysis was performed on 23 children with fungal BSI following chemotherapy for AL in three hospitals in Fujian Province,China,from January 2015 to December 2023.Their clinical features and prognosis were analyzed.Results Among all children following chemotherapy for AL,the incidence rate of fungal BSI was 1.38%(23/1 668).At the time of fungal BSI,87%(20/23)of the children had neutrophil deficiency for more than one week,and all the children presented with fever,while 22%(5/23)of them experienced septic shock.All 23 children exhibited significant increases in C-reactive protein and procalcitonin levels.A total of 23 fungal isolates were detected in peripheral blood cultures,with Candida tropicalis being the most common isolate(52%,12/23).Caspofungin or micafungin combined with liposomal amphotericin B had a relatively high response rate(75%,12/16),and the median duration of antifungal therapy was 3.0 months.The overall mortality rate in the patients with fungal BSI was 35%(8/23),and the attributable death rate was 22%(5/23).Conclusions Fungal BSI following chemotherapy in children with AL often occurs in children with persistent neutrophil deficiency and lacks specific clinical manifestations.The children with fungal BSI following chemotherapy for AL experience a prolonged course of antifungal therapy and have a high mortality rate,with Candida tropicalis being the most common pathogen.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To investigate the correlations between the bone mineral densities and biomechanical properties on different layers of the cancellous bone in the proximal tibia.Methods:Quantitative CT was conducted of the 15 specimens of adult male tibia. Based on the artificial destruction levels at the trabecular bone on the tibial plateau, the 15 specimens were randomly divided into 3 groups ( n=5): group A (cancellous bone on the 1.5 cm layer below the articular cartilage), group B (cancellous bone on the 3.0 cm layer under the articular cartilage) and group C (cancellous bone on the 0 to 3 cm range of the subchondral bone). After standing positions were simulated in the 3 sets of specimens, they were connected to a biomechanical testing machine. Twenty-four sites were selected and subjected to a vertical load of 600 N. Strain values and overall displacement values of the specimens were recorded before and after trabecular bone destruction. The correlations were analyzed between bone density and displacement values in groups A and B. The strain values before and after trabecular bone destruction, as well as the overall deformation values of the specimens were compared between the 3 groups. Results:The bone densities of specimens in groups A and B were negatively correlated with the displacement values before and after destruction ( P<0.05). Comparisons of strain values at the 24 sites before and after trabecular bone destruction within 3 groups: There were statistically significant differences in the strain values at 8 sites between before and after trabecular bone destruction in group A ( P<0.05). Of the 8 sites, 6 showed increased strains which were mainly concentrated around the insertion point of the anterior cruciate ligament and the medial tibial plateau. There were statistically significant differences in the strain values between before and after trabecular bone destruction at 3 sites in group B ( P<0.05). The strains at all the 3 sites increased, mainly concentrated behind the surface below the level of destruction. There were statistically significant differences in the strain values at 10 sites in group C between before and after trabecular bone destruction ( P<0.05). Of the 10 sites, 5 showed a decrease in the strain which was concentrated above the destruction plane, and 5 showed an increase in the strain which was concentrated below the destruction plane. The overall deformation values of the specimens in groups A, B, and C were (0.033±0.003) mm, (0.015±0.003) mm, and (0.066±0.007) mm, respectively, showing statistically significant differences between the 3 groups ( P<0.05) as well as between any 2 groups ( P<0.05). Conclusions:Bone mineral density in the cancellous bone of the proximal tibia has some value in assessment of the bone strength. Destruction of the proximal tibial cancellous bone can significantly change the strain distribution on the proximal tibia. The proximal cancellous bone of the tibia plays a key role in stress support and load conduction.

The population aging and the coming of the information era are accompanied with the growing incidence of spinal degenerative diseases, which result in heavy social and economic burdens. Under the guidance of the tendon-bone theory, rich experience has been accumulated in the prevention and diagnosis of spinal degenerative diseases with traditional Chinese medicine(TCM), which demonstrates unique advantages. China's government has placed people's health in the strategic position of development, providing a favorable environment for the realization of healthy aging. The Healthy China 2030 advocates special actions for healthy bones. As China is facing an important period of demographic transition, the Traditional Chinese Medicine for Bone Health Program has emerged, combining the needs of the national health strategy and the advantages of TCM. This paper discusses the background and significance of the program. According to the theory of five body constituents and the characteristics of musculoskeletal system diseases, this paper constructs a theoretical system of "tendon-meridian-muscle-bone-marrow" to explain the structure and function of the musculoskeletal system. From the holistic view of TCM, this system shows not only the structure and function of the musculoskeletal system but also the patterns of disease development and the mechanism of TCM treatment. The system facilitates the research on not only the comorbidities related to bone health but also the occurrence, development, and outcome of diseases. In the management of chronic degenerative diseases, attention should be paid to the establishment and improvement of the disease prevention and control system in addition to the disease treatment alone. Finally, this paper introduces the characteristic advantages of TCM in the whole process of prevention, diagnosis, treatment, rehabilitation, and health maintenance of spinal degenerative diseases, aiming to enrich the connotation of the tendon-bone theory, provide ideas and implementation strategies for TCM clinical practice, and ultimately achieve the effective management of the diagnosis and treatment of spinal degenerative diseases.
Humans ; Medicine, Chinese Traditional ; Spinal Diseases/prevention & control* ; Drugs, Chinese Herbal/therapeutic use* ; China ; Bone and Bones/drug effects*

This study aimed to investigate the effect of aucubin(AU) on injury of nucleus pulposus cells and extracellular matrix(ECM) degradation and its mechanism. The nucleus pulposus cell injury model was established by interleukin-1β(IL-1β) and treated with AU or phosphatidylinositol 3-kinase(PI3K) inhibitor LY294002. CCK-8 experiment was conducted to test cell proliferation. EdU staining method was employed to detect cell injury. Flow cytometry was used to detect cell apoptosis. Western blot was used to detect protein levels of cleaved-caspase-3, B-cell lymphoma(Bcl-2), Bcl-2 associated X protein(Bax), type Ⅱ collagen(collagen Ⅱ), aggregation proteoglycans(aggrecan), PI3K, and mammalian target of rapamycin(mTOR). qPCR was used to detect the rRNA level of 5S, 18S, and 28S. Ethynyluridine was used to label nascent RNA. The results showed that IL-1β could significantly cause injury of nucleus pulposus cells and increase the apoptosis rate of nucleus pulposus cells and the expression of apoptosis protein cleaved-caspase-3 and Bax. At the same time, IL-1β down-regulated the expression of anti-apoptotic protein Bcl-2 and collagen Ⅱ and aggrecan, the main components of ECM. On this basis, AU intervention could improve the injury of nucleus pulposus cells, reduce the apoptosis of nucleus pulposus cells and the expression of cleaved-caspase-3 and Bax, and increase the expression of Bcl-2, collagen Ⅱ, and aggrecan. Compared with IL-1β, AU could up-regulate the phosphorylation level of PI3K and mTOR, and LY294002 could reverse the injury of nucleus pulposus cells and improve ECM degradation induced by AU. In addition, AU also could save lowered rRNA levels of 5S, 18S, and 28S induced by IL-1β and improve RNA synthesis. PI3K inhibitor LY294002 intervention could reduce the promoting effect of AU on ribosome biogenesis. The above results suggest that AU can improve the injury of nucleus pulposus cells and ECM degradation, and its mechanism of action is related to its activation of the PI3K/mTOR pathway to promote ribosome biogenesis.
Nucleus Pulposus/cytology* ; Extracellular Matrix/drug effects* ; Animals ; Iridoid Glucosides/pharmacology* ; Apoptosis/drug effects* ; Interleukin-1beta/metabolism* ; Phosphatidylinositol 3-Kinases/genetics* ; Rats ; Cell Proliferation/drug effects* ; TOR Serine-Threonine Kinases/genetics* ; Rats, Sprague-Dawley ; Humans ; Signal Transduction/drug effects* ; Caspase 3/genetics* ; Proto-Oncogene Proteins c-bcl-2/genetics*