ObjectiveTo investigate the effect and underlying mechanism of the Wulao Qisun prescription on pathological new bone formation in ankylosing spondylitis （AS）. MethodsSynovial fibroblasts were isolated from the hip joints of AS patients and observed under a microscope to assess cell morphology. The cells were identified using immunofluorescence staining. The isolated AS fibroblasts were divided into blank group， low drug-containing serum group， medium drug-containing serum group， high drug-containing serum group， and positive drug group. After drug intervention， cell proliferation was measured using the cell counting kit-8 （CCK-8） assay to observe fibroblast growth and determine the optimal intervention time. Alkaline phosphatase （ALP） activity was measured using the alkaline phosphatase assay. Protein expression of osteocalcin （OCN）， osteopontin （OPN）， and runt-related transcription factor 2 （Runx2） was detected by Western blot. The mRNA expression levels of Wnt5a， β-catenin， and Dickkopf-1 （DKK-1） were measured by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， each drug-containing serum group of Wulao Qisun prescription and the positive drug group inhibited the proliferation of AS fibroblasts and reduced ALP expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription downregulated β-catenin mRNA expression （P<0.05）. The medium and high drug-containing serum groups and the positive drug group significantly downregulated Wnt5a and β-catenin mRNA expression （P<0.05， P<0.01）， with the positive drug group showing the most pronounced effect （P<0.01）. The high drug-containing serum group and the positive drug group significantly upregulated DKK-1 mRNA expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription inhibited the expression of OPN and Runx2 proteins （P<0.05， P<0.01）， while the medium and high drug-containing serum groups and the positive drug group inhibited the expression of OCN， OPN， and Runx2 proteins （P<0.05， P<0.01）. ConclusionThe Wulao Qisun prescription can inhibit the proliferation and osteogenic differentiation of AS fibroblasts， thereby delaying the formation of pathological new bone in AS. The possible mechanism involves the regulation of Wnt/β-catenin-related gene expression， further inhibiting the transcription of downstream target genes.

OBJECTIVE: To investigate the midterm clinical efficacy of medial patellofemoral complex (MPFC) reconstruction for recurrent patellar dislocation with high-grade trochlear dysplasia. METHODS: A retrospective analysis was carried out among adult patients who underwent arthroscopically assisted MPFC reconstruction between January 2014 and December 2020. Dejour classification was evaluated to grade trochlear dysplasia; tibial tubercle-trochlear groove (TT-TG) distance and Insall-Salvati index were measured. Preoperative and postoperative patient-reported outcome measures (PROMs) were compared, including International Knee Documentation Committee (IKDC) score, Kujala score, Lysholm score and Tegner score. Information regarding returning-to-sport rate, re-instability events and complications was collected. Patellar tilt (PT), lateral patellar displacement (LPD) and bisect offset (BSO) ratio were measured based on axial computed tomography before and after surgery to assess the patellofemoral congruence. RESULTS: A total of 46 MPFC reconstructions in 43 patients were enrolled, including 16 male and 27 female. Mean age at surgery was (22.2±7.6) years (range: 14-44 years). Mean follow-up was (49.9±22.6) months (range: 18-102 months). The percentages of Dejour B, C and D dysplasia were 37.0% (17/46), 43.5% (20/46), and 19.6% (9/46), respectively. Mean Insall-Salvati index was 1.2±0.2 (range: 0.85-1.44), and mean TT-TG distance was (19.6±3.5) mm (range: 10.6-28.7 mm). At latest follow-up, there were significant improvements in all PROMs (P < 0.001): IKDC score, from 56.3±15.1 to 86.2±8.1; Kujala score, from 58.9±15.6 to 92.6±5.4; Lysholm score, from 63.7±15.0 to 94.0±5.7; Tegner score, from 3.1±1.4 to 4.7±1.4, and there were no significant differences in the improvements of the scores between the patients with Dejour B, C and D dysplasia. Overall, ninety percent of the patients returned to their preoperative sports level. One patient reported a postoperative subluxation, while no cases of infection, limited range of motion or patella fracture were observed. PT, LPD and BSO ratio were all significant altered (P < 0.001) after MPFC reconstruction. CONCLUSION Arthroscopically assisted MPFC reconstruction yielded satisfactory midterm clinical results for recurrent patellar dislocation with high-grade trochlear dysplasia. No significant differences of improvements in knee function were observed among the three types of high-grade trochlear dysplasia.
Humans ; Patellar Dislocation/surgery* ; Male ; Female ; Adult ; Arthroscopy/methods* ; Retrospective Studies ; Adolescent ; Young Adult ; Patellofemoral Joint/surgery* ; Recurrence ; Plastic Surgery Procedures/methods* ; Patella/surgery* ; Treatment Outcome

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

BACKGROUND:In recent years,the incidence of hyperuricemia caused by purine metabolism disorders has been increasing,which can induce inflammatory responses and lead to renal injury. OBJECTIVE:To explore the role and mechanism of solute carrier family 2 member 12(SLC2A12)in hyperuricemia-related renal injury. METHODS:Renal tubular cells(HK2 cells)were divided into five groups:HK2 group,HK2+uric acid group,HK2+uric acid+NC group,HK2+uric acid+siSLC2A12 group,and HK2+uric acid+siSLC2A12+MK-2206 group.HK2 cells were treated with uric acid and transfected with siRNA SLC2A12,followed by MK-2206 treatment to inhibit AKT expression.Cell proliferation was detected by CCK-8 assay.Apoptosis was detected by TUNEL assay.qRT-PCR and western blot assay were used to detect fibrogenic factors as well as activation of the AKT/FOXO3a pathway.The concentrations of inflammatory cytokines were measured by enzyme-linked immunosorbent assay. RESULTS AND CONCLUSION:(1)Uric acid treatment inhibited cell proliferation and promoted cell apoptosis in the HK2+uric acid group compared with the HK2 group.The proliferative ability of cells in the HK2+uric acid+siSLC2A12 group was further decreased and apoptotic cells were further increased compared with the HK2 group.Compared with the HK2+uric acid+siSLC2A12 group,the HK2+uric acid+siSLC2A12+MK-2206 group showed an increase in cell proliferation and a decrease in apoptotic cells.(2)Compared with the HK2 group,the connective tissue growth factor(CTGF),α-smooth muscle actin(α-SMA)and transforming growth factor beta(TGF-β)expressions increased in the HK2+uric acid group;CTGF,α-SMA and TGF-β expression further increased in the HK2+uric acid+siSLC2A12 group.Compared with the HK2+uric acid+siSLC2A12 group,the CTGF,α-SMA and TGF-β expressions decreased.(3)Compared with the HK2 group,the expression of p-AKT,FOXO3a,and p-FOXO3a elevated in the HK2+uric acid group;the expression of p-AKT further increased,while the expression of FOXO3a and p-FOXO3a decreased in the HK2+uric acid+siSLC2A12 group.Compared with the HK2+uric acid+siSLC2A12 group,p-AKT expression decreased;FOXO3a and p-FOXO3a expression increased in the HK2+uric acid+siSLC2A12+MK-2206 group.(4)Compared with the HK2 group,interleukin-6,interleukin-1 β,and tumor necrosis factor α levels increased in the HK2+uric acid group;interleukin-6,interleukin-1 β,and tumor necrosis factor α levels further increased in the HK2+uric acid+siSLC2A12 group.Compared with the HK2+uric acid+siSLC2A12 group,interleukin-6,interleukin-1 β,and tumor necrosis factor α levels diminished in the HK2+uric acid+siSLC2A12+MK-2206 group.(5)These findings indicate that SLC2A12 may protect against hyperuricemia-induced renal injury by counteracting uric acid-induced tubular fibrosis and inflammation through activation of the FOXO3a pathway.

Objective:To investigate the diagnosis, treatment and prognosis of ovarian yolk sac tumor (OYST).Methods:The clinicopathological data and follow-up data of 12 patients with OYST admitted to the Affiliated Hospital of Qingdao University from January 2013 to December 2020 were retrospectively analyzed, and the diagnosis, treatment and prognosis of OYST patients were summarized.Results:(1) The age of 12 patients with OYST ranged from 11 to 37 years, with a median age of 20 years. At the first visit, all 12 patients had pelvic masses. Reasons for seeing a doctor: 6 cases of abdominal distension and abdominal pain, 4 cases of mass in the lower abdomen, 1 case of vaginal bleeding, and 1 case of appendicitis. International Federation of Obstetrics and Gynecology (FIGO) 2014 staging: 4 cases in stage Ⅰa, 2 cases in stage Ⅰc, 1 case in stage Ⅱc, 4 cases in stage Ⅲc, and 1 case in stage Ⅳb. (2) All 12 patients were examined by color Doppler ultrasound before operation, among which 10 cases showed unilateral adnexal masses and 2 cases bilateral adnexal masses. The median maximum diameter of tumor was 16.5 cm (range: 6.0-28.0 cm). The preoperative levels of alpha fetoprotein (AFP) in 12 patients (all >1 210 μg/L) were significantly higher than normal (<25 μg/L). Among the 11 patients with cancer antigen 125 (CA 125) detection results, 9 patients showed elevated serum CA 125 levels. (3) Among the 12 patients, 8 young infertile patients who needed to preserve their reproductive function underwent appendectomy, 3 infertile patients underwent staged surgery for ovarian malignant germ cell tumor, and only one bilateral lesion and infertile patient underwent unsatisfactory staged surgery for ovarian malignant germ cell tumor. Of the 12 patients, 11 patients were given combined chemotherapy regimen of bleomycin, cisplatin, and etoposide (BEP) after operation. One patient without chemotherapy developed metastasis 3 months after operation, and was given BEP chemotherapy, and her condition was controlled. (4) The deadline for follow-up was December 31st, 2022, and the median follow-up time was 60 months (range: 25-115 months). All the 12 patients survived without tumor during the follow-up period, and the median disease-free survival time was 84.5 months (range: 25-115 months). Conclusions:OYST mostly occurs in children and young women. Color Doppler ultrasound examination and serum AFP and CA 125 detection have diagnostic value for OYST. Surgical treatment after diagnosis of OYST includes surgery to preserve reproductive function and timely and standardized chemotherapy after operation. The prognosis of patients is good regardless of stage.

Propensity score can improve the efficiency and accuracy of clinical trials， and has been widely used in many fields such as comparison of efficacy evaluation， exploration of disease occurrence factors， and monitoring of adverse drug reactions. At present， the propensity scoe has application prospects in traditional Chinese medicine （TCM） monotherapy intervention， complex intervention and integrated Chinese and Western medicine intervention research， and it is a good auxiliary tool for real-world study. By analysing the cha-racteristics of clinical research in TCM， the authors believed that， firstly， the application of propensity score can acce-lerate the progress of clinical efficacy evaluation research in TCM， contribute to the collection of high-level clinical evidence， and promote the development and promotion of TCM therapies； Secondly， under the background of big data resources， propensity score has good application prospects in assisting TCM prescription analysis， drug safety and adverse reaction monitoring， and large-scale cohort studies in TCM； thirdly， in the process of clinical practice， propensity scoring method may face problems such as inappropriate method selection， incorrect judgement or measurement of confounding factors， and unreasonable interpretation or extrapolation of results.

Objective To screen small molecule inhibitors of Fusobacterium nucleatum （Fn） based on commercially available compound libraries, and investigate their anti-colorectal cancer activities under Fn intervention in order to obtain novel anti-colorectal cancer lead compounds. Methods The promotion of colorectal cancer proliferation on organoid was validated by Fn. Secondly, the effects of anti-Fn compounds on their in vitro anticancer activity under Fn’s co-incubation with colorectal cancer HCT116 cell were comparative investigated. Finally, in vivo anticancer efficacy of highly active compounds on nude mouse colon cancer HCT116 transplanted tumor under the intervention of Fn was evaluated by gavage. Results Fn could significantly promote the proliferation of rectal cancer organoids. 9 anti-Fn active compounds could significantly enhance their in vitro anticancer activity under Fn’s co-incubation with HCT116 cells. Methotrexate had the strongest anti-cancer activity with IC₅₀ as 0.03 μmol/L. The combined use of methotrexate (0.5 mg/kg) and PD-1 (5.0 mg/kg) had a stronger anti-tumor effect than their standalone use. Conclusion As new small molecule inhibitor of Fn, methotrexate exhibited good in vitro and in vivo anti-colorectal cancer activity against HCT116 cells and nude mouse xenografts under Fn intervention, which showed the foundation for subsequent structural optimization, and could be expected to expand the new indications of methotrexate.

BACKGROUND:The anterior cruciate ligament has unique nonlinear mechanical properties under a complex physiological loading environment.Elastin is an important contributor to the mechanical properties of the anterior cruciate ligament,but its mechanical response to the anterior cruciate ligament under axial tension is not clear. OBJECTIVE:To quantitatively analyze the effect of elastin on the tensile mechanical response of the anterior cruciate ligament. METHODS:Elastase solution and control buffer were prepared.The porcine anterior cruciate ligament samples were prepared into small-size samples and randomly soaked in 0,0.1,1.0,2.0,5.0,and 10.0 U/mL elastase solution for 6 hours,and other small samples of the same size were soaked in 2 U/mL elastase solution for 0,1,3,6,9,and 12 hours.To determine suitable soaking conditions for elastin-targeted enzymes and verify the digestive effect,histological staining was used to compare the effects of enzyme treatment on tissue structure and composition.The ligament samples were randomly divided into elastase-treated group and PBS group,and immersed in 2 U/mL elastase solution and PBS buffer for 6 hours,respectively.A mechanical tensile test was performed before and after immersion. RESULTS AND CONCLUSION:(1)The biochemical results showed that being treated in 2 U/mL elastase solution for 6 hours could reduce the elastin content by 31.1%,and had no significant effect on other mechanical-related components in the tissue.(2)The histological results showed that elastase was able to penetrate the tissue,and the loose degree of tissue increased after treatment.(3)In the mechanical results before and after treatment,the mechanical properties of the PBS group decreased significantly,only the low-tension elastic modulus increased significantly and the initial length increased significantly in the elastase-treated group.(4)The intergroup comparison results showed that there was no significant difference between the two groups in pre-treatment,but the low-tension elastic modulus,initial slopes,saturated slopes,and initial length of the elastase-treated group after treatment were significantly higher than those in the PBS group.(5)These results suggest that elastin degradation significantly affects the biomechanical properties of the anterior cruciate ligament and further complements our understanding of the structure-function relationship of the anterior cruciate ligament.

Objective:To systematically investigate the short-term efficacy of total knee arthroplasty in the treatment of osteoarthritis coupled with fixed patellar dislocation.Methods:A retrospective analysis was conducted on a cohort of 11 patients diagnosed with knee osteoarthritis and fixed patellar dislocation who underwent total knee arthroplasty at Panzhihua Central Hospital from January 2018 to October 2021. The cohort comprised 4 males and 7 females, aged 63.45±4.76 years (range, 56-70 years), all of whom underwent unilateral surgery. There were 5 left and 6 right knees, with a body mass index of 23.20±2.02 kg/m 2 (range, 20.8-27.6 kg/m 2) and a disease course of 12.63±4.81 years. According to the American Society of Anesthesiologists classification, 9 cases were categorized as grade II, and 2 cases as grade III. Recovery of patellar trajectory during total knee arthroplasty, using medial synovial flap transposition to repair lateral joint capsule. Preoperative and postoperative assessments included knee joint range of motion, Knee Society score (KSS), University of California Los Angeles (UCLA) score, and visual analogue scale (VAS). Results:All 11 patients were followed up for a period of 28.64±4.01 months (range, 24-36 months). Two patients exhibited subcutaneous fat liquefaction locally after surgery, which resolved following dressing changes. All wounds achieved primary healing. Two of them developed intramuscular vein thrombosis after surgery and were cured after anticoagulant treatment. The range of motion of the knee joint increased from 63.18°±17.07° before surgery to 104.55°±16.80° at the last follow-up, with a statistically significant difference ( t=14.041, P<0.001). The KSS score increased from 38.00±6.78 points to 80.91±5.65 points, with a statistically significant difference ( t=16.472, P<0.001). The UCLA score increased from 3.18±1.17 to 6.73±1.35, with a statistically significant difference ( t=9.694, P<0.001). The VAS decreased from 6.09±0.94 points to 2.32±0.64 points, with a statistically significant difference ( t=16.600, P<0.001). At the last follow-up, imaging examinations showed no cases of patellar subluxation or dislocation, no tearing or breakage of the knee extension device, and no infection or loosening around the prosthesis. Conclusion:Utilizing medial synovial flap transposition for repairing the lateral joint capsule proves to be an effective technique for key capsule repair. Total knee arthroplasty for osteoarthritis combined with fixed patellar dislocation demonstrates satisfactory early clinical outcomes.

Objective:To investigate the efficacy of a trauma-integrated treatment program for severe traumatic brain injury and its effect on patients' coagulation and neurological functions.Methods:A total of 114 patients with severe traumatic brain injury who received treatment at the Department of Trauma Surgery at the Jinhua Municipal Central Hospital from April 2020 to October 2022 were retrospectively included in this study. The patients were divided into two groups based on different treatment protocols: Group A ( n = 57 patients) received the conventional emergency treatment protocol, while Group B ( n = 57 patients) received the trauma-integrated treatment protocol. The emergency treatment efficiency (including emergency room stay time, waiting time for auxiliary examinations, waiting time for multidisciplinary consultations, and time from emergency to surgery), coagulation function (prothrombin time, thrombin time, activated partial thromboplastin time), neurological function (National Institutes of Health Stroke Scale), incidence of complications (stress ulcers, pulmonary infections, hypernatremia, and cerebral salt-wasting syndrome), and prognosis were compared between the two groups. Results:The emergency room stay time, waiting time for auxiliary examinations, waiting time for multidisciplinary consultations, and time from emergency to surgery in Group B [(21.94 ± 6.21) minutes, (5.78 ± 1.12) minutes, (10.58 ± 2.47) minutes, and (8.57 ± 2.01) minutes] were significantly shorter than those in Group A [(32.59 ± 6.83) minutes, (9.46 ± 2.57) minutes, (17.36 ± 3.71) minutes, (15.36 ± 4.49) minutes, t = 8.71, 9.91, 11.48, 10.42, all P < 0.001]. After treatment, the prothrombin time, thrombin time, and activated partial thromboplastin time in Group B [(19.78 ± 2.32) seconds, (21.16 ± 2.60) seconds, (39.35 ± 4.60) seconds] were significantly shorter than those in Group A [(21.83 ± 2.63) seconds, (23.28 ± 2.95) seconds, (42.16 ± 5.52) seconds, t = 4.41, P < 0.001, t = 4.07, P < 0.001, t = 2.95, P = 0.002]. The National Institutes of Health Stroke Scale score after treatment in Group B [(13.55 ± 3.17) points] was significantly lower than that in Group A [(18.36 ± 3.83) points, t = 7.30, P < 0.001]. The incidence of complications in Group B [7.02% (4/57)] was significantly lower than that in Group A [22.81% (13/57), χ2 = 5.60, P = 0.018]. The rate of good prognosis in Group B [66.67% (38/57)] was significantly higher than that in Group A [47.37% (27/57), χ2 = 4.33, P = 0.037]. Conclusion:The trauma-integrated treatment protocol is effective for severe traumatic brain injury, as it improves emergency treatment efficiency, enhances coagulation and neurological functions, reduces the incidence of complications, and is beneficial for prognosis.