Hippo signaling is a highly conserved pathway central to diverse cellular processes. Dysregulation of this pathway not only leads to developmental abnormalities but is also closely related to the occurrence and progression of various cancers. Recent studies have uncovered that, in addition to the classical signaling cascade regulation, biomolecular condensates formed via phase separation play a key role in the spatiotemporal regulation of Hippo signaling. In this review, we provide a summary of the latest research progress on the regulation of the Hippo signaling pathway by phase separation, with a particular focus on transcriptional activation mediated by Yes-associated protein (YAP)/transcriptional coactivator with post-synaptic density-95, disks-large, and zonula occludens-1 (PDZ)-binding domain (TAZ) condensates. Furthermore, we discuss the utility of chemical crosslinking combined with mass spectrometry to analyze the TAZ condensate interactome and examine the role of the protein fused in sarcoma (FUS) in modulating the biophysical properties of TAZ condensates, which in turn influence their transcriptional activity and pro-tumorigenic functions. These insights not only advance our understanding of Hippo signaling but also offer new perspectives for therapeutic interventions targeting diseases linked to dysregulated YAP/TAZ activity.
Humans ; Signal Transduction ; Hippo Signaling Pathway ; Protein Serine-Threonine Kinases/physiology* ; Animals ; Biomolecular Condensates/metabolism* ; Transcription Factors/metabolism* ; YAP-Signaling Proteins ; Adaptor Proteins, Signal Transducing/metabolism* ; Neoplasms ; Transcriptional Activation ; Intracellular Signaling Peptides and Proteins/metabolism*

Objective:To explored the correlation between anxiety and depression and cerebral small vessel disease(CSVD)in the elderly patients with type 2 diabetes mellitus(T2DM), and analyzed the influencing factors of anxiety and depression.Methods:Clinical data of 101 elderly T2DM inpatients admitted to the Department of Endocrinology, the Second Affiliated Hospital of Fujian Medical University from July 2020 to December 2021 were retrospectively analyzed, and clinical features, laboratory tests and examination data were collected.The Hamilton Depression Scale and the Hamilton Anxiety Scale were used for assessment, with a cut-off value of 14 points for anxiety and 8 points for depression.Brain scans were performed using 3.0T magnetic resonance scanner, including T1WI sequence, T2WI sequence, 3D-FLAIR sequence, SWI sequence.According to the total MRI load scoring standard of CSVD proposed by Staals, MRI imaging changes of CSVD, namely lacunar foci(LIs), cerebral microhemorrhage(CMBs), perivascular space(PVSs), and white matter high signal(WMHs), were analyzed and scored respectively.Load score ≥1 was defined as CSVD group.According to the above criteria, the enrolled patients were divided into depression group and anxiety group, and the clinical characteristics, biochemical test data and MRI imaging characteristics of CSVD between the two groups were analyzed by single factor analysis, and then Spearman correlation analysis was used to analyze the related factors of the elderly T2DM with anxiety and depression.Binary logistic analysis was used to analyze the risk factors of depression and anxiety in the elderly patients with T2DM.Results:Compared with the non-depressed group, the elderly T2DM patients with depression were older, more female, and the incidence of WMHs and DWMHs was higher( P<0.05).Compared with the non-anxious group, the incidence of WMHs and DWMHs in the elderly T2DM patients with anxiety group was higher( P<0.05).Spearman correlation analysis showed that age( r=0.224, P=0.024), WMHs( r=0.231, P=0.020), PWMHs( r=0.201, P=0.044), DWMHs( r=0.274, P=0.006)was positively correlated with depression in the elderly T2DM, while gender( r=-0.225, P=0.024)、ALT( r=-0.208, P=0.037)、AST( r=-0.204, P=0.041)was negatively correlated with depression in the elderly T2DM.WMHs( r=0.213, P=0.033)and DWMHs( r=0.270, P=0.006)were positively correlated with anxiety in the elderly T2DM.Binary logistic regression analysis showed that gender( OR=0.359, 95% CI: 0.130-0.990, P=0.048), DWMHs(OR=4.373, 95% CI: 1.290-14.828, P=0.018)were the influencing factors for the elderly T2DM patients with depression, and DWMHs( OR=5.000, 95% CI: 1.444-17.317, P=0.011)was the influencing factors for the elderly T2DM patients with anxiety. Conclusions:DWMHs is closely related to the onset of depression and anxiety in the elderly T2DM patients, suggesting that CSVD may be involved in the development of depression and anxiety in the elderly T2DM patients.

BACKGROUND:It is generaly believed that the spine wil be extended, and vertebral muscle atrophy, bone loss of vertebral body, increased height and area of intervertebral disc, changes of composition of intervertebral disc wil occur in the condition of weightlessness. These are likely to be the cause of high incidence of low back pain. OBJECTIVE:To observe changes in lumbar spine bone microstructure analysis of simulated weightlessness on rhesus lumbar spine biomechanics. METHODS:Fourteen young rhesus monkeys were randomly divided into two groups: control group (n=7;free activities in the cage during the experiment), and experimental group (n=7; the use of head-down-10° on a special bed by bundle lying to simulate weightlessness). RESULTS AND CONCLUSION:(1) The results of Micro-CT examination: in the experimental group, structure model index in trabecular bone of increased. Trabecular bone changed from plate-like to the rod-like change. The intersection number of bone tissue in unit length to non-bone tissue declined. The average width of the canal between the trabecular bone increased, suggesting that there have been signs of osteoporosis in the experimental group. (2) Under an optical microscope, in the experimental group, bone hyperplasia line was disordered and irregular. Thick endplate trabecularbone became smal, shalow, and arranged substantialy perpendicular to the direction of trabecular bone and cartilage endplate. The closer the endplate surface, the smaler trabecular bone was. Compared with the control group, these smal trabecular bones were thin and curved. Bone marrow cavity was oval. The degree of the connection between the trabecular bones is poor, reflecting the structural characteristics of significant osteoporosis. (3) It is indicated that weightlessness affected the biomechanical properties of rhesus lumbar motion unit.

OBJECTIVETo explore use of interleukin-10 receptor (IL-10R) gene mutation in diagnosis and pathogenesis of neonatal inflammatory bowel disease (IBD) in 2 suspected cases.

METHODTwo cases of sibling brothers who had suspected IBD from Guangzhou Women and Children's Medical Center Affiliated to Guangzhou Medical University during the year 2010-2014 were enrolled in the study. The proband, male, 26 days old, weight 3.73 kg, presented with recurrent fever, increased stool frequency since 9 days of age, and was hospitalized at the age of 6 months in 2014. The proband's brother, male, 6 months old, weight 8 kg, had repeated bloody and mucous diarrhea for more than five months, recurrent fever five days, and was hospitalized in 2010. The blood samples were collected from the children and their families for IL-10 receptor genes including IL-10 receptor α subunit (IL-10RA) and β subunit (IL-10RB) PCR amplification. Reverse transcription polymerase chain reaction (RT-PCR) was used to amplify the proband IL-10RA transcripts. Sequencing was performed on the PCR products forward and reversely. Western blot analysis was used for protein expression of the proband and normal control's IL-10RA and P-STAT3 (Tyr705) expression after IL-10 stimulation, TNF-α level was detected using Human TNF-α ELISA Kit after PBMC was cultured and stimulated.

RESULTThe proband and his brother were IBD patients. Genome sequencing showed mutation in c.537G>A, namely the exon 4 and intron 4 connections changed CA/GT for CG/GT. Sequencing of the RT-PCR products and T-A clone showed that the mutation was (c.519-537del GGTGCCGGGAAACTTCAC, p.LYS173ASNfs*7), as the splice mutation. Two gene mutations were novel mutation. The parents were the mutations carrier. Both of the children were compound heterozygous mutations in IL-10RA. The Western blot analysis showed that the patient and normal children can express IL-10RA protein, however, the function of IL-10RA had obvious defects in the patient, IL-10RA downstream signaling pathways P-STAT3 had no expression. The average level of TNF-α secreted by PBMC after LPS + IL-10 co-stimulation in patient was significantly increased as compared with control group ((2 100±356) vs. (200±50) ng/L, t=9.154, P=0.001), suggesting that interleukin-10-dependent negative feedback regulation is disrupted in the patient.

CONCLUSIONIL-10 receptor mutations can cause neonatal-IBD, for which common treatment effect is poor. Early diagnosis and allogeneic stem-cell transplantation performed may save the children's life.

BACKGROUND:During ordinary plate fixation, the soft tissues around the fracture of the proximal humerus are nearly stripped to impact blood supply, and moreover, an ordinary steel plate cannot meet with the fixed requirements for severe osteoporosis, large bone defects and comminuted fractures. OBJECTIVE: To observe the functional recovery and complications in middle-aged patients with proximal humeral fractures undergoing stainless steel locking plate implantation. METHODS:From March 2011 to March 2014, 48 patients with proximal humeral fractures were treated in the 306th RESULTS AND CONCLUSION: The 48 patients were folowed up for 6-17 years, and the mean healing time was (15.3±1.2) weeks. At the last folow-up, the Neer scores were excelent in 12 cases, good in 22 cases, fair in 11 cases and poor in 3 cases, with an excelent-good rate of 71%. After internal fixation, there was one case of Hospital of PLA, including 20 males and 28 females, with an average age of 58 years. Of the 48 cases, there were 9 cases of Neer 2 fractures, 26 cases of Neer 3 fractures, and 13 cases of Neer 4 cases, al of which belonged to closed injuries. Al the patients were subject to locking plate implantation for repair of fractures of the proximal humerus, and evaluated based on Neer scores. soft tissue infection, two cases of traumatic arthritis, and no bone ununion and osteomyelitis. These findings suggest that the stainless steel locking plate implantation for repair of fractures of the proximal humerus can achieve a good anatomic reduction under minimaly invasive conditions and produce a stable rehabilitation environment for the soft tissue around the shoulder joint by internal fixation. Hence, the factures can recover faster with less complications. The stainless steel locking plate implantation can obtain good achievements in the repair of proximal humeral fractures of Neer 2, 3 as wel as Neer 4 in young patients with good bone quality.

BACKGROUND:Deep vein thrombosis after total knee arthroplasty has attracted increasing attention in recent years,but how to detect deep vein thrombosis in the early time in clinical practice remains unclear.Whether it is necessary to perform type-B ultrasonic or other invasive examination in lower limbs has become a hot issue.OBJECTIVE:To explore the significance of D-Dimer and fibrin degradation products in the prediction of deep vein thrombosis after total knee arthroplasty.METHODS:56 patients received total knee arthroplasty were colected from Department of Orthopedics,The 306th Hospital of Chinese PLA,between December 2012 and February 2014.The D-Dimer and fibrin degradation products were dynamicaly monitored before operation and at 1,3,5,7,10 days post-operation.Al the patients received type-B ultrasonic examination in double lower limbs at 10 days post-operation,and divided into thrombus group and non-thrombus group.The D-Dimer and fibrin degradation products in the two groups were compared.RESULTS AND CONCLUSION:Deep vein thrombosis was found in 13 cases by ultrasonic-B postoperation,D-Dimer and fibrin degradation products showed no significant difference between the two groups at 1 week after operation (P＞0.05),but the difference was significant at 10 days (P＜0.01).D-Dimer and fibrin degradation products index should be monitored dynamicaly for at least 10 days after operation,which is helpful for the earlydiagnosis of thrombosis.

Objective To compare the diagnostic significance of pleural SLPI,IFN-γ and ADA for differenti-ating TPE from pleural effusions with the other etiologies. Methods Pleural effusion samples were obtained from 93 patients who were divided into the following groups: tuberculous pleural effusion,malignant pleural effusion, bacterial pleural effusion and transudative pleural effusion. The pleural effusion and/or serum levels of SLPI , IFN-γand ADA were determined. Results 1.The concentrations of SLPI, IFN-γand ADA in tuberculous pleural effusion was higher than that in malignant group, bacterial group and transudative group. 2. The diagnostic value of SLPI, IFN-γor ADA for the diagnosis of tuberculous PE is high respectively. The combinations of SLPI, IFN-γand/or ADA gained the more valuable diagnostic performance. Conclusion Pleural SLPI, IFN-γand ADA may be helpful for the differential diagnosis of tuberculous pleural effusion and the other pleural effusion. The combinations of SLPI or/and IFN-γor/and ADA further increased diagnostic value.

BACKGROUND:The treatment difficulties of thoracolumbar angular kyphosis surgery are:low correction rate, hard to rebuild sagittal plane, easily induce neurological complications, postoperative loss of balance, high incidence of pseudarthrosis and postoperative loss of correction degree.
OBJECTIVE:To explore the safety and efficacy of modified posterior vertebral column resection osteotomy and bilateral pedicle screw combined with echelon tight closure spinal cord technique and implant fixation for severe spinal angular kyphosis.
METHODS:A total of 87 severe spinal angular kyphosis patients, 36 males and 51 females, who were treated in the Department of Orthopedics, the 306 Hospital of Chinese PLA from January 2006 to December 2013, were enrol ed in this study. They underwent posterior vertebral column resection, bilateral pedicle screw combined with echelon tight closure spinal cord, and implant fixation. Kyphosis, spinal sagittal imbalance, offset rate towards trunk side, operation time and intraoperative blood loss were observed before and after treatment.
RESULTS AND CONCLUSION:The preoperative average kyphosis was 90.1° (31°-138°). The postoperative average kyphosis was 27.9° (15°-57°). The improvement rate was 76%. The improvement rate of trunk sagittal offset was 76%. Intraoperative blood loss was 800-3 000 mL, and average blood loss was 2 300 mL. The operation time was 5-7 hours, averagely 5.9 hours. Before treatment, two patients affected neurologic symptoms in double lower extremity, and their Frankel classification was grade C and became grade E after treatment. Al patients were fol owed up for 9-57 months. Bony fusion was achieved in al patients. No complications of spinal cord injury appeared, and no orthopedic angle missing occurred. These results indicate that during posterior vertebral column resection for treating severe angular stiffness of the thoracic kyphosis, blood vessels could be maintained greatly. Blood vessel injury-induced ischemic changes in spinal cord and ischemic reperfusion injury could be avoided. To reduce hemorrhage and to keep effective blood volume in patients with low body mass are effective for early recovery after treatment. Bilateral pedicle screw combined with echelon tight closure spinal cord technique greatly protected spinal cord cells against injury. We should pay attention to the protection and loose of nerve root to avoid postoperative nerve root irritation. Sufficient bone fusion ensures kyphosis correction, avoids spine lateral offset, and plays a key role in spinal function and postoperative orthopedic effect.

BACKGROUND:Severe spinal angular kyphosis aggravated spinal cord injury and early degeneration, even caused incomplete paralysis or complete paralysis. Surgical treatment is the only solving approaches and method, but it is difficult, exhibits high risk, and easily affects postoperative complications. OBJECTIVE:To analyze the science and effectiveness of posterior vertebral column resection osteotomy combined with step correction in treatment of stiff angular kyphosis based on biomechanical principle. METHODS:A total of 90 cases underwent posterior vertebral column resection osteotomy combined with bilateral pedicle screw spinal cord gradual y shortening echelon tight closure and orthopedic fixation were selected, including 37 males and 52 females, at the average age of 47 years. Kyphotic angle, spinal sagittal imbalance, trunk side offset rate, operation time, intraoperative blood loss were compared and analyzed before and after treatment. RESULTS AND CONCLUSION:The kyphotic angles were 31°-138° (averagely 90.1°) preoperatively and 10°-90° (averagely 41.6°) postoperatively, with an improvement rate of 65%. The distance from C 7 plumb line to the S 1 upper edge was averagely 5.2 mm, with a correction rate of 73%. Intraoperative blood loss was 1 200-6 000 mL, averagely 2 089 mL. Operation time was 212-470 minutes, averagely 326 minutes. The patients were fol owed up for 20 to 35 months after the surgery. Osteotomy segments had achieved bone fusion in al patients, and no complications of spinal cord injury or orthopedic angle loss appeared. These data verified that in the accordance with cellbiomechanics and spinal biomechanical principles, bilateral pedicle screw spinal cord gradual y shortening echelon tight closure and orthopedic fixation protected utmost spinal cord cells against injury in the correction of thoracolumbar angular kyphosis. There is sufficient basis for cellphysiology and it accorded biomechanical and physiological characteristics. During the surgery, we should pay attention to protection and release of nerve root and avoid postoperative corresponding nerve root irritation. Ful fusion ensures kyphosis correction and avoids spine lateral offset, is an effective safeguard for the recovery of spinal function and postoperative orthopedic effect.

BACKGROUND:Knee society score of Peking Union Medical Col ege has been promoted and used in the 306th Hospital of PLA for 2 years and we have accumulated some clinical data.
OBJECTIVE:To analyze the stability and feasibility for suitable clinical medical practice of knee society score of Peking Union Medical Col ege.
METHODS:Fifty-five patients with osteoarthritis of the knee were included, and the patients were divided into
three groups:the preoperative group;3 months postoperative fol ow-up group;6 months postoperative fol ow-up group. The measurement results obtained by the application of the scale were compared to those of the Western Ontario and McMaster Universityies Ostroarthritis Index, visual analog scale, and hospital for special surgery
score, and then knee society score goodness-of-fit analysis was performed based on the structural equation model.
RESULTS AND CONCLUSION:Knee society score performance assessment of the signs and symptoms of
osteoarthritis of the knee patients was positively correlated with the pain severity of visual analog scale score;the overal knee society score of the patients after 6-month fol ow-up was significantly improved compared with that before treatment. The knee society score after 3-and 6-month fol ow-up was significantly higher than that before treatment, and the score was quite with the hospital for special surgery score. The overal assessment of the knee society score after treated for 3 and 6 months was improved for more than grade Ⅰ, the visual analog scale
score was decreased for more than 30%. The pain assessment items and physiological functional assessment items of Western Ontario and McMaster Universityies Ostroarthritis Index after 6-month fol ow-up were
significantly better than those before treatment (P<0.05);the visual analog scale score was poor after 3-month fol ow-up, and there was significant difference in visual analog scale score before and after treatment which was related with the pain level;the score accompanied by function and joint stiffness was significantly improved. The knee society score of Peking Union Medical Col ege obtained four dimensions of 22 assessment projects, and the
goodness-of-fit analysis showed that the scale had good goodness which had scientific nature and application value.