OBJECTIVE: To identify and validate novel biomarkers for the early diagnosis of sepsis-associated acute kidney injury (SA-AKI) and precise continuous renal replacement therapy (CRRT) using proteomics. METHODS: A prospective multicenter cohort study was conducted. Patients with sepsis admitted to five hospitals in Taizhou City of Zhejiang Province from April 2019 to December 2021 were continuously enrolled, based on the occurrence of acute kidney injury (AKI). Sepsis patients were divided into SA-AKI group and non-SA-AKI group, and healthy individuals who underwent physical examinations during the same period were used as control (NC group). Peripheral blood samples from participants were collected for protein mass spectrometry analysis. Differentially expressed proteins were identified, and functional enrichment analysis was conducted on these proteins. The levels of target proteins were detected by enzyme linked immunosorbent assay (ELISA), and the predictive value of target protein for SA-AKI were evaluated by receiver operator characteristic curve (ROC curve). Additionally, sepsis patients and healthy individuals were selected from one hospital to externally verify the expression level of the target protein and its predictive value for SA-AKI, as well as the accuracy of CRRT treatment. RESULTS: A total of 37 patients with sepsis (including 19 with AKI and 18 without AKI) and 31 healthy individuals were enrolled for proteomic analysis. Seven proteins were identified with significantly differential expression between the SA-AKI group and non-SA-AKI group: namely cystatin C (CST3), β ₂-microglobulin (β ₂M), insulin-like growth factor-binding protein 4 (IGFBP4), complement factor I (CFI), complement factor D (CFD), CD59, and glycoprotein prostaglandin D2 synthase (PTGDS). Functional enrichment analysis revealed that these proteins were involved in immune response, complement activation, coagulation cascade, and neutrophil degranulation. ELISA results demonstrated specific expression of each target protein in the SA-AKI group. Additionally, 65 patients with sepsis (38 with AKI and 27 without AKI) and 20 healthy individuals were selected for external validation of the 7 target proteins. ELISA results showed that there were statistically significant differences in the expression levels of CST3, β ₂M, IGFBP4, CFD, and CD59 between the SA-AKI group and non-SA-AKI group. ROC curve analysis indicated that the area under the curve (AUC) values of CST3, β ₂M, IGFBP4, CFD, and CD59 for predicting SA-AKI were 0.788, 0.723, 0.723, 0.795, and 0.836, respectively, all exceeding 0.7. Further analysis of patients who underwent CRRT or not revealed that IGFBP4 had a good predictive value, with an AUC of 0.84. CONCLUSIONS Based on proteomic analysis, CST3, β ₂M, IGFBP4, CFD, and CD59 may serve as potential biomarkers for the diagnosis of SA-AKI, among which IGFBP4 might be a potential biomarker for predicting the need for CRRT in SA-AKI patients. However, further clinical validation is required.
Humans ; Sepsis/complications* ; Acute Kidney Injury/blood* ; Proteomics ; Prospective Studies ; Biomarkers/blood* ; Male ; Female ; beta 2-Microglobulin/blood* ; Middle Aged ; Cystatin C/blood* ; Aged

Purpose: Numerous barriers hinder individuals with mental illness from seeking medical assistance in rural regions, yet a comprehensive understanding of these challenges remains elusive. This metasynthesis aims to understand the barriers and facilitators in medical help-seeking among rural individuals with mental illness. Methods: We systematically searched seven databases [PubMed, CINAHL, Medline (OVID), PsycINFO (OVID), Cochrane, Embase, and ProQuest] in May 2023 and included the studies if they reported the barriers or/and facilitators to seek healthcare in rural patients with mental illness. We conducted hand search and citation search on Google Scholar for literature supplements. Thematic analysis was employed. Results: The study included 27 articles reporting on the barriers and facilitators to seeking medical help in this population from 2007 to 2023. We ultimately identified themes at three levels: navigating the terrain of vulnerability and empowerment (the individual with mental illness), navigating the terrain of external environment (the external environment) and connectivity within the healthcare ecosystem for mental health (the health service system). Conclusions We must design more effective strategies to improve mental healthcare access for rural patients, considering cultural nuances and health service utilization patterns. This requires a multi-level approach, tailored to the unique needs of diverse populations.

Objective·To construct a cervical vertebra image segmentation model by using a diffusion model with the Transformer deep learning algorithm,and evaluate its segmentation performance,to address the clinical challenge of accurately assessing complex changes in skeletal morphology during the growth and developmental peaks of malocclusion.Methods·Accurate cervical vertebra segmentation was performed on cephalometric radiographs from 185 orthodontic patients(44 cases from the Stomatological Hospital of Chongqing Medical University and 141 cases from the Stomatological Hospital of Xi'an Jiaotong University)by using a method combining Transformer and diffusion models.First,the images were preprocessed to crop out the cervical vertebra region of interest,and all data were randomly divided into a training set(79.6%)and a test set(20.4%).The diffusion model and a conditional model based on U-Net were utilized for feature extraction,with a Transformer module introduced to learn the interaction between noise and semantic features.Multi-scale images were fused to enhance fine structure and boundary texture features in low-contrast images.The proposed method was compared with U-Net and SOLOv2 methods.The segmentation performance was quantitatively evaluated by two metrics,Dice Similarity Coefficient(DSC)and Intersection over Union(IoU),and also qualitatively assessed through physicians'manual annotations and model visualization results.Results·The cervical vertebra segmentation method based on Transformer and diffusion models achieved DSC and IoU scores of 93.3%and 87.5%,respectively,significantly outperforming the U-Net and SOLOv2 methods(with improvements of 3.0%and 4.1%in DSC,and 5.2%and 7.1%in loU,respectively).Despite the longer processing time for a single image,segmentation accuracy was significantly improved.Compared with U-Net and SOLOv2,the proposed method also showed higher stability and robustness in processing complex,low-contrast and blurred-boundary images,and was able to accurately segment the cervical vertebrae with clear boundaries and complete structures.Conclusion·The Transformer-based diffusion model for cervical vertebra segmentation can enhance the edge and texture features in cervical vertebra images and recognize the boundaries of different vertebrae more easily.Thus,automatic,accurate,and robust cervical vertebra segmentation results are achieved,which can assist in cervical vertebral maturation analysis.

Objective·To construct a cervical vertebra image segmentation model by using a diffusion model with the Transformer deep learning algorithm,and evaluate its segmentation performance,to address the clinical challenge of accurately assessing complex changes in skeletal morphology during the growth and developmental peaks of malocclusion.Methods·Accurate cervical vertebra segmentation was performed on cephalometric radiographs from 185 orthodontic patients(44 cases from the Stomatological Hospital of Chongqing Medical University and 141 cases from the Stomatological Hospital of Xi'an Jiaotong University)by using a method combining Transformer and diffusion models.First,the images were preprocessed to crop out the cervical vertebra region of interest,and all data were randomly divided into a training set(79.6%)and a test set(20.4%).The diffusion model and a conditional model based on U-Net were utilized for feature extraction,with a Transformer module introduced to learn the interaction between noise and semantic features.Multi-scale images were fused to enhance fine structure and boundary texture features in low-contrast images.The proposed method was compared with U-Net and SOLOv2 methods.The segmentation performance was quantitatively evaluated by two metrics,Dice Similarity Coefficient(DSC)and Intersection over Union(IoU),and also qualitatively assessed through physicians'manual annotations and model visualization results.Results·The cervical vertebra segmentation method based on Transformer and diffusion models achieved DSC and IoU scores of 93.3%and 87.5%,respectively,significantly outperforming the U-Net and SOLOv2 methods(with improvements of 3.0%and 4.1%in DSC,and 5.2%and 7.1%in loU,respectively).Despite the longer processing time for a single image,segmentation accuracy was significantly improved.Compared with U-Net and SOLOv2,the proposed method also showed higher stability and robustness in processing complex,low-contrast and blurred-boundary images,and was able to accurately segment the cervical vertebrae with clear boundaries and complete structures.Conclusion·The Transformer-based diffusion model for cervical vertebra segmentation can enhance the edge and texture features in cervical vertebra images and recognize the boundaries of different vertebrae more easily.Thus,automatic,accurate,and robust cervical vertebra segmentation results are achieved,which can assist in cervical vertebral maturation analysis.

ObjectiveTo investigate the efficacy of Bushen Shengxue prescription and Yiqi Yangxue prescription in the treatment of chronic aplastic anemia and the effect on T cell subsets and the expression of T-box expressed in T cells （T-bet） and GATA binding protein 3 （GATA3）. MethodA total of 585 patients with chronic aplastic anemia who were treated in 19 hospitals in China from May 2018 to June 2021 were enrolled. With the prospective， double-blind and randomized control methods， the patients were randomized into three groups： kidney deficiency group， Qi and blood deficiency group， and control group. The three groups were respectively treated with Bushen Shengxue prescription granule， Yiqi Yangxue prescription granule， and Placebo （half the dose of Bushen Shengxue formula granules）. In addition， all of them were given oral cyclosporin and androgen. The treatment lasted 6 months， with 3 months as a course. The blood routine indexes， T cell subsets， and fusion genes T-bet and GATA3 before and after treatment were analyzed， and the safety indexes were monitored. ResultDuring the observation， a total of 75 cases dropped out and 18 were rejected. Finally， 161 cases in the kidney deficiency group， 164 in the Qi and blood deficiency group， and 167 in the control group were included. After 6 months of treatment， the total effective rate was 98.8% （159/161） in the kidney deficiency group， which was higher than the 79.9% （131/164） in the Qi and blood deficiency group （χ²=30.135， P<0.01） and the 61.7% （103/167） in the control group （χ²=70.126， P<0.01）. The total effective rate was higher in the Qi and blood deficiency group than in the control group （χ²=13.232， P<0.01）. After treatment， the hemoglobin （HGB） content increased significantly in three groups （P<0.05） as compared with that before treatment， particularly the kidney deficiency group （P<0.01）. After treatment， the white blood cell （WBC） count and platelet （PLT） count in the kidney deficiency group and the control group increased compared with those in the Qi and blood deficiency group （P<0.01）. There was no specific difference in neutrophils （ANC） after treatment among the three groups. At the same time point， the level of T helper type 1 （Th1） cells， Th1/Th2 ratio （P<0.05）， level of CD4⁺， and CD4⁺/CD8⁺ ratio （P<0.05） were significantly low in the kidney deficiency group among three groups. There was no significant difference in CD19^-， HLA/DR⁺， and CD25⁺ between the kidney deficiency group and the other two groups， but the T-bet of the kidney deficiency group and the control group was lower than that of the Qi and blood deficiency group （P<0.05）. ConclusionBushen Shengxue prescription exerts therapeutic effect on the aplastic anemia by improving the immunoregulatory mechanism， inhibiting the activity of immune system， modulating T cell subsets， suppressing Th1 and CD4⁺， and promoting bone marrow hematopoiesis. Moreover， it is safe with little side effects， which is worthy of further promotion.

Objective:To introduce the surgical method of Ortho-Bridge system (OBS) in the treatment of distal femoral fractures in elderly patients and investigate its clinical effect.Methods:From January 2018 to July 2021, 24 elderly patients who suffered distal femoral fractures were treated with bilateral OBS. There were 8 males and 16 females aging from 62 to 87 years, with an average age of 72.6 years. It included 15 cases of simple distal femoral fractures. According to AO classification, there were one case of A1, two of A2, five of A3, two of C1, three of C2 and two of C3. Nine cases of femoral periprosthetic fractures after total knee arthroplasty (TKA) were classified as type II according to rorabeck's classification. After operation, all patients were guided to perform knee joint functional exercise and to measure the range of motion of the knee joint. Then imaging examinations were used to evaluate the fracture healing and measure the femoral-tibial and femoral angles. The American Hospital for Special Surgery (HSS) knee joint scoring system was used to evaluate the knee function.Results:All 24 patients successfully completed the operation. The operation time was 84-115 min, with an average of 96.6 min; the intraoperative blood loss was 150-335 ml, with an average of 240 ml. All patients were followed up for 8-17 months, with an average of 13.6 months. Except for 1 case of nonunion due to few primary bone grafts, which required secondary bone grafting, the other 23 cases achieved bone union. The healing time was 3.5-6 months, with an average of 4.6 months. At 1, 3, and 6 months after operation and at the last follow-up, the flexion angles of knee were 92.2°±10.2°, 98.6°±13.3°, 106.4°±13.7°, 115.7°±15.3°, and the extension angles were -4.7°±4.1°, -1.2°±4.2°, 0.7°±4.5°, 1.8°±4.6°, respectively; and all differences were statistically significant ( F=17.03 and 12.68, P<0.001). The knee flexion and extension angles at the last follow-up were greater than 1, 3, and 6 months after operation, and the differences were statistically significant ( P<0.001). The femoral-tibial angle was 171.2°±2.4° and 170.7°±3.2°, and the femoral angle was 80.3°±1.7° and 79.6°±2.1°, respectively, at the immediate postoperative and last follow-up, with no significant difference. The HSS scores at 1, 3, 6 months after operation and at the last follow-up were 71.5±7.5, 74.6± 9.3, 78.9±10.4 and 84.7±9.4 respectively, with significant difference ( F=9.17, P<0.001). At the last follow-up, the HSS score was higher than that at 1, 3, and 6 months after the operation, and the differences were statistically significant ( P<0.001), and the knee function was evaluated according to the HSS scoring system: excellent in 12 cases, good in 9, fair in 3, with an excellent and good rate of 88% (21/24). There was no OBS crack or fixation failure in all patients, and no prosthetic loosening and instability occurred in patients with periprosthetic femoral fractures after TKA. Statistical analysis of the data at the last follow-up between the distal femoral fracture group and the periprosthetic femoral fracture group after TKA showed that the knee flexion function and HSS score of the periprosthetic femoral fracture group after TKA (126.8°±3.7°, 92.2±4.1) were both better than the simple distal femur fracture group (108.9°±15.7°, 80.2±8.8). The difference was statistically significant ( t=4.22, 4.52, P<0.05). One patient had incision fat liquefaction and healed after debridement; bone nonunion occurred in 1 case, which healed after iliac bone grafting. Conclusion:Double OBS has a good clinical effect in the treatment of distal femoral fractures in the elderly, especially in patients with periprosthetic femoral fractures after TKA.

Objective:To compare the biomechanical parameters of Ortho-Bridge system (OBS) and locking compression plate+locking attachment plate (LCP+LAP) in the fixation of femoral periprosthetic type B1 fracture.Methods:The same periprosthetic type B1 fracture of human femur were made, including simple fracture model and comminuted fracture model, 12 in each. And the simple fracture models were randomly divided into 6 pieces of OBS system fixation group and 6 pieces of LCP+LAP system fixation group, and the complex fracture models were also randomly divided into 6 pieces of OBS system fixation group and 6 pieces of LCP + LAP system fixation group. Then the four groups of models were tested by axial compression and torsion tests, and the stiffness of the models under axial compression and torsion angle of the models under torsion test were collected. The axial compression failure test was carried out to collect the vertical load of the ultimate failure test. The axial stiffness, torsion angle and axial failure load of OBS and LCP+LAP fixed simple and comminuted fractures were statistically analyzed by t test. Results:For the test of fixed simple fracture, there was no significant difference ( t=0.535, P=0.522) in the axial stiffness between the OBS group (868.87±157.14 N) and the LCP+LAP group (904.53±44.76 N), whereas the results of torsion test showed that the LCP+LAP group had a higher torsion angle 7.17°±0.52° than the OBS group 5.45°±0.44° ( t=5.616, P<0.001); When fixing comminuted fractures, the OBS group had a higher axial stiffness (145.33±10.34 N) than the LCP+LAP group (84.15±8.94 N) ( t=10.961, P<0.001), but the LCP+LAP group had a higher torsion angle 7.75°±1.17° than the OBS group 5.23°±0.31° ( t=4.652, P=0.001). Ultimate failure test data showed that the failure pressure of OBS fixed group (4 967.49±132.88 N) was higher than LCP+LAP group (3 967.41±145.16 N) ( t=12.447, P<0.001). In the LCP+LAP group, there was destruction of the contact cortex at the fracture site, while in the OBS group, there was destruction of the contact cortex at the fracture site as well as fractures around the proximal fixation screw. Conclusion:OBS group has similar axial compression resistance to LCP+LAP group, but better torsion resistance than LCP+LAP group when it is used to fix B1 simple fracture around femoral prosthesis. When comminuted fracture is fixed, the axial compression resistance and torsion resistance of OBS group are better than LCP+LAP group. The stress is dispersed during OBS fixation, which can better avoid the failure of internal fixation during early functional exercise.

Objective To investigate the expression of N-myc downstream regulated gene-2 (NDRG2) on renal fibrosis in unilateral ureteral obstruction(UUO) rat model and the mechanism of renal fibrosis.Methods Forty-eight male Wistar rats (120-150g)were randomly divided into two groups:the sham-operation group (n =24)underwent the left ureteral dissection,the UUO group (n =24)underwent the left ureteral ligation.At the 3,7,14,21day after the operation,6 rats from each of the group were sacrificed and the obstructive kidneys were collected.The histopathological changes were observed through HE and Masson staining.E-cadherin and α-SMA were detected by Western blot and immunohistochemistry.NDRG2 were detected by Western blot,immunohistochemistry and real-time PCR.Results There is not diffenrence in the sham group at anytime.Compared with the sham-group,the fibrosis was obvious in UUO group.The protein of E-cadherin decreased(P ＜ 0.05) and α-SMA increased(P ＜0.05).The expression of NDRG2 in UUO group was lower than that in the sham group.The OD of immunohistochemistry was detected by ImagePro Plus 6.0.OD of NDRG2 was the lowest[(14.33 ± 2.45) x 10-3] in 21d group.The western blot showed that the ratio of NDRG2 to β-actin was the lowest(0.03 ± 0.01) in 21d group.The mRNA of NDRG2 decreased obverously in UUO group (P ＜ 0.05).Conclusion NDRG2 decreases in UUO group and NDRG2 might be involved in the pathologic process of renal fibrosis.

Objective: To investigate the clinicopathologic features, diagnostic and differential diagnostic aspects of pigmented microcystic chromophobe renal cell carcinoma (ChRCC). Methods: Five cases of pigmented microcystic ChRCC were collected at Zhejiang Provincial People′s Hospital from January 2013 to January 2018. The clinical features, gross and histological appearances, immunohistochemistry and prognosis were analyzed and the relevant literature was reviewed. Results: There were 3 men and 2 women with age range of 45 years to 72 years (mean 57 years). All tumors were incidentally identified by imaging examinations. Grossly, the tumors were well-demarcated and showed diameters ranging from 1.8 cm to 4.0 cm(mean 2.9 cm). On cross section, the tumors were brown to gray tan with solid cut-surface mixed with multiple cysts of variable sizes. Hemorrhage was common, central scar was not seen. Microscopically, the tumors were composed predominantly of irregular and variable-sized microcystic or tubulocystic patterns, with extensive cribriform structures formation and focal adenomatous rearrangements seen in one case each, and focal pseudo-papillary structures (lacking true fibro-vascular cores) seen in two cases. Microscopic calcifications and psammoma bodies were present in all tumors. Four tumors composed mostly of eosinophilic cells whereas 1 predominated in plant-like cells. Brown pigmentations, either intracytoplasmic or extracytoplasmic, were noted in all five cases. The tumor cells had irregular, low-grade nuclei (Paner grade: 1) frequently with binucleation and perinuclar halos. Tumor necrosis or sarcomatous transformation was not seen. By immunohistochemistry, the tumor cells expressed CK, EMA, and E-cadherin diffusely and strongly in five cases; and CK7 and CD117 diffusely in four cases. They were negative for vimentin, CD10, CA9, AMACR/P504s, TFE3, HMB45, Melan A, S-100 protein, synaptophysin and chromogranin. Partial nephrectomies were performed for all five patients; there was no tumor recurrences or metastases at a follow-up of 2 to 55 months (mean, 17 months). Conclusions Pigmented microcystic ChRCC is a rare histological variant of ChRCC with relatively indolent behavior, and shows morphologic heterogeneity which can elicit a wide range of differential diagnoses. Careful attentions to search for typical features of classic ChRCC with the use of immunohistochemistry can help to distinguish this tumor from its many mimickers.

Objective: To investigate the clinicopathologic characteristics, immunophenotypes, and differential diagnostic features of extra-pleural solitary fibrous tumor (SFT) with uncommon histology. Methods: Seven cases of extra-pleural SFT with uncommon histology were collected during January 2015 and December 2016 in Zhejiang Provincal People′s Hospital; the clinical and radiologic features, histomorphology, immunophenotype and prognosis were analyzed. EnVision method was used for immunohistochemical staining of STAT6, CD34 and other differential diagnosis associated markers. Results: There were five male and two female patients, age from 23 to 54 years (mean=39 years). Three tumors were located in the soft tissue of head and neck, two in trunk subcutaneous soft tissue, one in sella region, and one in the kidney. Grossly the tumors ranged from 0.4 to 8.0 cm (mean=3.1 cm). Microscopically, all three head and neck cases resembled giant cell angiofibroma/giant cell subtype SFT, and one case showed sheet-like pattern of the multinucleated syncytial cells, creating a biphasic arrangement similar to myofibroma. Both truncal tumor resembled lipomatous type SFT, with one similar to dermatofibrosarcoma protuberans and the other to atypical spindle cell lipomatous tumor. The sella tumor showed morphology of a conventional SFT with high grade sarcomatous transformation. The renal tumor demonstrated a malignant SFT with entrapped benign renal tubules, mimicking a biphase synovial sarcoma or a malignant mixed epithelial and stromal tumor. By immunohistochemistry, all seven SFTs showed diffuse and strong nuclear reactivity to antibody against STAT6. Conclusions Extra-pleural SFTs show a significant heterogeneity of morphology and biological behavior which could cause differential confusion.Careful attention to its characteristic histomorphology with the use of STAT6 immunohistochemistry can help distinguish this tumor from its many mimickers.