Objective:Glioblastoma(GBM)and brain metastases(BMs)are the two most common malignant brain tumors in adults.Magnetic resonance imaging(MRI)is a commonly used method for screening and evaluating the prognosis of brain tumors,but the specificity and sensitivity of conventional MRI sequences in differential diagnosis of GBM and BMs are limited.In recent years,deep neural network has shown great potential in the realization of diagnostic classification and the establishment of clinical decision support system.This study aims to apply the radiomics features extracted by deep learning techniques to explore the feasibility of accurate preoperative classification for newly diagnosed GBM and solitary brain metastases(SBMs),and to further explore the impact of multimodality data fusion on classification tasks. Methods:Standard protocol cranial MRI sequence data from 135 newly diagnosed GBM patients and 73 patients with SBMs confirmed by histopathologic or clinical diagnosis were retrospectively analyzed.First,structural T1-weight,T1C-weight,and T2-weight were selected as 3 inputs to the entire model,regions of interest(ROIs)were manually delineated on the registered three modal MR images,and multimodality radiomics features were obtained,dimensions were reduced using a random forest(RF)-based feature selection method,and the importance of each feature was further analyzed.Secondly,we used the method of contrast disentangled to find the shared features and complementary features between different modal features.Finally,the response of each sample to GBM and SBMs was predicted by fusing 2 features from different modalities. Results:The radiomics features using machine learning and the multi-modal fusion method had a good discriminatory ability for GBM and SBMs.Furthermore,compared with single-modal data,the multimodal fusion models using machine learning algorithms such as support vector machine(SVM),Logistic regression,RF,adaptive boosting(AdaBoost),and gradient boosting decision tree(GBDT)achieved significant improvements,with area under the curve(AUC)values of 0.974,0.978,0.943,0.938,and 0.947,respectively;our comparative disentangled multi-modal MR fusion method performs well,and the results of AUC,accuracy(ACC),sensitivity(SEN)and specificity(SPE)in the test set were 0.985,0.984,0.900,and 0.990,respectively.Compared with other multi-modal fusion methods,AUC,ACC,and SEN in this study all achieved the best performance.In the ablation experiment to verify the effects of each module component in this study,AUC,ACC,and SEN increased by 1.6%,10.9%and 15.0%,respectively after 3 loss functions were used simultaneously. Conclusion:A deep learning-based contrast disentangled multi-modal MR radiomics feature fusion technique helps to improve GBM and SBMs classification accuracy.

ObjectiveThis study aimed to evaluate the clinical efficacy of Ruyi Zhenbaowan（RYZBW）in the treatment of initial and early knee osteoarthritis （KOA） through a prospective multicenter，randomized，double-blind，and placebo-parallel controlled trial. MethodFrom October 13^th， 2021 to December 25^th， 2021， 240 KOA subjects meeting the acceptance criteria were enrolled in 15 sub-centers including Wangjing Hospital， Chinese Academy of Chinese Medical Sciences， and they were randomly divided into observation group and control group， with 120 cases in each group. The intervention measures for the observation group were RYZBW + health education， and the intervention measures for the control group were RYZBW placebo + health education. The intervention period in both groups was four weeks， and they were followed up for four weeks after the intervention. The primary outcome measure was the total score of Western Ontario and McMaster University Osteoarthritis Index score （WOMAC score）， and the secondary outcome measures were the response rate of visual scale （VAS） pain score， WOMAC sub item scores （joint pain， joint stiffness， and joint function）， quality of life （SF-12） score， and traditional Chinese medicine （TCM） syndrome score. Result（1） Efficacy evaluation. The marginal model results showed that the observation group was better than the control group in improving the WOMAC total score and WOMAC pain score in the treatment of KOA with RYZBW， and the difference was statistically significant （P<0.05）. There was no significant difference between the two groups in improving VAS score response rate， WOMAC function score， WOMAC stiffness score， SF12-PCS （quality of life-physical health） score， SF12-MCS （quality of life-mental health） score， and TCM syndrome score. （2） Subgroup analysis. ① In terms of VAS score response rate， the response rate of the observation group was higher than that of the control group for subjects with baseline VAS score of （4， 5］， and the difference was statistically significant （P<0.05）. ② In terms of TCM syndrome score， for subjects aged ［56， 60］ and ［61， 65］， the decrease in total TCM syndrome score in the observation group was better than that in the control group， and the difference was statistically significant （P<0.05）. ConclusionTibetan medicine RYZBW has good clinical efficacy in improving WOMAC total score， VAS score response rate， WOMAC pain score， WOMAC function score， and TCM syndrome score for patients with initial and early KOA， which can fill the lack of Tibetan medicine RYZBW in the treatment of KOA and make a demonstration study for the inheritance and development of ethnic medicine.

Invasive fungal infections (IFIs) have been associated with high mortality, highlighting the urgent need for developing novel antifungal strategies. Herein the first light-responsive antifungal agents were designed by optical control of fungal ergosterol biosynthesis pathway with photocaged triazole lanosterol 14α-demethylase (CYP51) inhibitors. The photocaged triazoles completely shielded the CYP51 inhibition. The content of ergosterol in fungi before photoactivation and after photoactivation was 4.4% and 83.7%, respectively. Importantly, the shielded antifungal activity (MIC₈₀ ≥ 64 μg/mL) could be efficiently recovered (MIC₈₀ = 0.5-8 μg/mL) by light irradiation. The new chemical tools enable optical control of fungal growth arrest, morphological conversion and biofilm formation. The ability for high-precision antifungal treatment was validated by in vivo models. The light-activated compound A1 was comparable to fluconazole in prolonging survival in Galleria mellonella larvae with a median survival of 14 days and reducing fungal burden in the mouse skin infection model. Overall, this study paves the way for precise regulation of antifungal therapy with improved efficacy and safety.

KRAS‒PDEδ interaction is revealed as a promising target for suppressing the function of mutant KRAS. The bottleneck in clinical development of PDEδ inhibitors is the poor antitumor activity of known chemotypes. Here, we identified novel spiro-cyclic PDEδ inhibitors with potent antitumor activity both in vitro and in vivo. In particular, compound 36l (K _D = 127 ± 16 nmol/L) effectively bound to PDEδ and interfered with KRAS-PDEδ interaction. It influenced the distribution of KRAS in Mia PaCa-2 cells, downregulated the phosphorylation of t-ERK and t-AKT and promoted apoptosis of the cells. The novel inhibitor 36l exhibited significant in vivo antitumor potency in pancreatic cancer patient-derived xenograft (PDX) models. It represents a promising lead compound for investigating the druggability of KRAS‒PDEδ interaction.

Objective:To investigate the clinical efficacy of the vascularised semi-split fibular flap with lateral approach in ankle fusion.Methods:A total of 54 patients who underwent ankle fusion through the lateral menstrual approach by the Department of Trauma and Micro Orthopaedics, Zhongnan Hospital of Wuhan University from June 2015 to December 2020 was retrospectively analysed. Of the 54 patients, 27 patients who underwent ankle fusion with a semi-split fibular flap carrying blood supply were assigned to the fibular flap group, while other 27 patients who had ankle fusion with lateral plate were assigned to the plate group. The ankle fusions for both groups were performed by the same surgical team. The clinical efficacy of the 2 groups was evaluated by the success rate of bone fusion, the American Orthopedic Foot and Ankle Surgery(AOFAS) Ankle-Hindfoot Score System, and the Visual analog score(VAS). All the patients entered the postoperative follow-up at outpatient clinic.Results:The follow-up lasted for 12-24 months, with an average of 15 months. At 6 months after surgery, 24 patients in the fibular flap group achieved osseous union with 88.9% in the success rate of bone fusion. While 17 patients in the plate group achieved osseous union, with the success rate of bone fusion at 63.0%. There was a statistically significant difference between the groups( P<0.05). At 1 year after surgery, all 27 patients in the fibular flap group achieved bony union, with a 100% of the success rate of bone fusion, while 23 patients in the plate group achieved bony union at a 85.2% success rate of bone fusion, with 4 patients failed to heal. The difference was statistically significant( P<0.05). The AOFAS scores of the fibular flap group were 41.3±12.0, 65.6±5.6, and 79.1±7.0 before operation, at 6 months after operation and 1 year after operation, respectively, while the scores for the plate group at the same time were 40.8±11.3, 64.5±4.1 and 69.3±7.2. There was no significant difference in the scores between the groups before surgery and at 6 months after the operation ( P>0.05). The scores at 1 year after surgery in the fibular flap group was significantly higher than the plate group, and there was a statistically significant difference( P<0.05). The preoperative VAS score in the fibular flap group was 7.6±1.3, while it was 7.5±1.1 in the plate group. There was no significant difference between the groups in VAS score( P>0.05). However, the VAS score at 1 year after surgery was found at 1.8±0.9 in the plate group, and 1.9±0.8 in the fibular flap group and the difference between groups was statistically significant( P<0.05). Conclusion:The surgical procedure of semi-split fibular flap through the lateral approach has lower complications and higher success rate in ankle fusion in comparison with those of the fusion with lateral plate. Thus, further clinical investigations can be considered.

Metabolic-associated fatty liver disease (MAFLD), which is previously known as non-alcoholic fatty liver disease (NAFLD), represents a major health concern worldwide with limited therapy. Here, we provide evidence that ferroptosis, a novel form of regulated cell death characterized by iron-driven lipid peroxidation, was comprehensively activated in liver tissues from MAFLD patients. The canonical-GPX4 (cGPX4), which is the most important negative controller of ferroptosis, is downregulated at protein but not mRNA level. Interestingly, a non-canonical GPX4 transcript-variant is induced (inducible-GPX4, iGPX4) in MAFLD condition. The high fat-fructose/sucrose diet (HFFD) and methionine/choline-deficient diet (MCD)-induced MAFLD pathologies, including hepatocellular ballooning, steatohepatitis and fibrosis, were attenuated and aggravated, respectively, in cGPX4-and iGPX4-knockin mice. cGPX4 and iGPX4 isoforms also displayed opposing effects on oxidative stress and ferroptosis in hepatocytes. Knockdown of iGPX4 by siRNA alleviated lipid stress, ferroptosis and cell injury. Mechanistically, the triggered iGPX4 interacts with cGPX4 to facilitate the transformation of cGPX4 from enzymatic-active monomer to enzymatic-inactive oligomers upon lipid stress, and thus promotes ferroptosis. Co-immunoprecipitation and nano LC-MS/MS analyses confirmed the interaction between iGPX4 and cGPX4. Our results reveal a detrimental role of non-canonical GPX4 isoform in ferroptosis, and indicate selectively targeting iGPX4 may be a promising therapeutic strategy for MAFLD.

Objective:To investigate the clinical characteristics and treatment of orbital cellulitis in neonates.Methods:Clinical data of 6 neonates with orbital cellulitis were retrospectively analyzed.Newborn orbital cellulitis cases were searched in PubMed, Web of Science, CNKI, Wanfang and VIP databases from the establishment of the database to July 1, 2019, and then relevant literature was reviewed.Results:(1)There were 4 males and 2 females.Five patients had fever.White blood cell(WBC), C-reactive protein(CRP) and procalcitonin(PCT) were significantly increased in 5 cases.Three cases were caused by the spread of infection of surrounding tissues, 2 cases were caused by bacteremia, and 1 case was suspected of vertical transmission from mother to child.Two cases of blood culture and 2 cases of purulent culture were positive.Microbial culture results were all staphylococcus aureus(SA). Four patients were treated with Ceftriaxone + Ampicillin and 2 cases with Ceftriaxone + Linezolid.Abscess incision and drainage were performed in 1 patient.All 6 cases were cured.(2)A total of 13 articles were retrieved, which reported 15 cases of neonatal orbital cellulitis were reported.Together with this 6 cases, 21 cases were analyzed.Periorbital swelling and fever were the main manifestations, and some children presented with simple fever or refuse milk and moan as the first symptom.WBC was significantly increased in most cases.The positive bacterial cultures of 19 cases all contained SA.Nineteen cases were treated with two or more antibiotics.According to the drug sensitivity test results, Vancomycin was used in 8 of the 12 foreign cases, and the third-generation cephalosporin combined with Ampicillin or Linezolid was mainly used in the domestic cases.Abscess incision and drainage were performed in 12 cases.Nineteen cases were cured, 1 case was left with spastic paralysis of limbs, and 1 case died.Conclusions:Orbital cellulitis is rare in the neonatal period, mainly due to the spread of periorbital tissue infection, bacteremia and vertical maternal and infant infection.It is sensitive to oral wiping.Invasive operations increase the risk of infection.The onset of the disease is insidious and ra-pid, and the diagnosis may be delayed in the neonatal period due to the lack of typical symptoms.SA is the chief pathogen.Antibiotics including staphylococci and streptococci should be used for treatment, and drug combination is often required.Incision and drainage should be performed timely for abscess formation.Early diagnosis, rational use of antibio-tics and prompt surgical treatment are necessary conditions for cure.Most of the patients have good prognosis, while the patients with cavernous sinus thrombosis have poor prognosis.

Objective: To detect potential mutation in a Chinese pedigree affected with congenital limb malformations. Methods: Clinical data was collected. Genomic DNA was extracted from peripheral blood samples of family members. The zone of polarizing activity regulatory sequence (ZRS) were amplified by PCR and subjected to direct sequencing. Results: Among the 13 individuals in this pedigree, there were 4 PPD patients, who were characterized by varying degrees of deformity. The female patients suffered triphalangeal thumb and preaxial polydactyly, while the male patients only had preaxial polydactyly. Only one patient had foot involvement. TA heterogeneous mutations was discovered in the ZRS (105C>G) in all patients, the same mutation was not detected in 2 healthy family members. Conclusion The inheritance pattern of PPD was autosomal dominant inheritance. There was a significant variability of symptoms among family patients. The heterozygous mutation of the ZRS (105C>G) probably underlie the disease.

OBJECTIVE: To detect potential mutation in a Chinese pedigree affected with congenital limb malformations. METHODS: Clinical data was collected. Genomic DNA was extracted from peripheral blood samples of family members. The zone of polarizing activity regulatory sequence (ZRS) were amplified by PCR and subjected to direct sequencing. RESULTS: Among the 13 individuals in this pedigree, there were 4 PPD patients, who were characterized by varying degrees of deformity. The female patients suffered triphalangeal thumb and preaxial polydactyly, while the male patients only had preaxial polydactyly. Only one patient had foot involvement. TA heterogeneous mutations was discovered in the ZRS (105C>G) in all patients, the same mutation was not detected in 2 healthy family members. CONCLUSION The inheritance pattern of PPD was autosomal dominant inheritance. There was a significant variability of symptoms among family patients. The heterozygous mutation of the ZRS (105C>G) probably underlie the disease.
Female ; Genetic Testing ; Hand Deformities, Congenital ; genetics ; Humans ; Limb Deformities, Congenital ; genetics ; Male ; Membrane Proteins ; genetics ; Pedigree ; Polydactyly ; genetics ; Thumb ; pathology

Objective To investigate the change of bone mineral density(BMD) in the early postpartum period and non-pregnant healthy women with the same age.Methods The American GE company's dual energy X-ray BMD instrument(DXA) was used to conduct the BMD detection at lumbar spine and femoral neck of 1 055 cases of postpartum women and 889 non-pregnant women.The subjects were grouped according to different ages and body mass index(BMI).Then the BMD value in each group was calculated and the results were statistically analyzed.Results The lumbar spine and femoral neck BMD values in difference age groups of the postpartum women appeared decrease as compared with the non-pregnant women group,the difference was statistically significant in the lumbar spine(P＜0.05).Conclusion BMD of early postpartum women in Chongqing area is significantly decreased.