Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Background Suicidal ideation serves as a sensitive predictive indicator for non-suicidal self-injury(NSSI)behavior,and NSSI behavior brings profound effects to both mental and physical health of senior high school students.Existing studies have made exploration on the relationship among insomnia,anxiety and NSSI behavior in the general population,but the internal mechanism of NSSI behavior in senior high school students with suicidal ideation requires further study.Objective To explore the pathway of anxiety between insomnia and NSSI behavior in senior high school students,so as to provide references for the intervention on NSSI behavior in such demographic.Methods From December 10 to 15,2021,cluster sampling was adopted to select 2 572 senior high school students across three senior high schools in Hubei Province as the research objects.Assessment was conducted by using Insomnia Severity Index(ISI),Generalized Anxiety Disorder Scale-7 item(GAD-7)and Adolescents Self-Harm Scale.Spearman correlation analysis was conducted to examine the correlation among scores of scales finished by senior high school students with suicidal ideation.Model 4 from the SPSS 20.0 Process 4.2 was employed to test the mediating path of anxiety between insomnia and NSSI behavior.Results A total of 2 421 valid questionnaires(94.13%)were recovered,which revealed 554 cases(22.88%)with suicidal ideation and 408 cases(16.85%)with NSSI behavior.The scores of ISI,GAD-7 and Adolescents Self-Harm Scale of senior high school students with suicidal ideation were higher than those of students without suicidal ideation(Z=17.124,20.611,21.314,P<0.01).As correlation analysis showed,the ISI score of senior high school students with suicidal ideation was positively correlated with scores of GAD-7 and Adolescents Self-Harm Scale(r=0.646,0.354,P<0.01),and GAD-7 score was positively correlated with the score of Adolescents Self-Harm Scale(r=0.375,P<0.01).Among senior high school students with suicide ideation,anxiety acted in a mediating role between insomnia and NSSI behavior,with effect value of 0.111(95%CI:0.053～0.185),accounting for 53.88%of the total effect.Conclusion Insomnia of senior high school students with suicidal ideation can not only directly affect NSSI behavior,but also indirectly affect NSSI behavior through anxiety.

Objective:To observe the therapeutic effect of autologous neurosensory retinal transplantation in repairing unhealed giant macular hole after pars plana vitrectomy (PPV).Methods:A prospective clinical study. From July 2022 to December 2023, 12 patients (12 eyes) with refractory large macular hole who received autologous neurosensory retinal transplantation treatment in Department of Ophthalmology of the First Affiliated Hospital of Zhengzhou University were selected for the study. The macular hole in affected eyes still did not close after PPV combined with inner limiting membrane removal or tamponade, and the diameter of macular hole were greater than 600 μm. All affected eyes received best corrected visual acuity (BCVA) and optical coherence tomography (OCT) examinations. The BCVA examination employed the international standard visual acuity chart, with results converted to logarithm of the minimum angle of resolution (logMAR) visual acuity for statistical analysis. During the surgery, a piece of healthy retinal neuroepithelial tissue, approximately 0.3 optic disc diameters larger than the macular hole, was removed from the upper retinal periphery and used as a graft. The graft was inserted into the macular hole with the aid of intraoperative OCT. Post-surgery, the vitreous cavity was filled with silicone oil or sterile air. The follow-up period after surgery was 6 months. The thickness of the retinal grafts was measured using the same equipment as before surgery at 3 days, 1, 3, and 6 months post-surgery. The primary focus was on observing the macular hole closure rate and changes in BCVA at 6 months post-operation. A paired t-test was used to compare BCVA before and after surgery. Results:In the sample of 12 cases (12 eyes), there were 5 males with 5 eyes and 7 females with 7 eyes. The mean age was (50.4±12.6) years. The mean macular hole diameter was (1 085.6±344.0) μm; The mean eye axis length was (27.64±4.19) mm. At 6 months after surgery, all affected eyes showed macular hole were completely closed (100.0%, 12/12). The thickness of the retinal graft was measured as (206.8±21.0), (170.8±23.3), (165.6±31.6), and (157.9±31.1) μm at 3 days, 1, 3, and 6 months post-surgery, respectively. At before and 6 months after surgery, the logMAR BCVA of the affected eyes was 1.28±0.39 and 0.95±0.22, respectively. The difference in logMAR BCVA before and after surgery was statistically significant ( t=3.40, P<0.05). Conclusion:Autologous neurosensory retinal transplantation could effectively improve the closure rate of refractory large macular hole and improve or stabilize vision in the short run.

Objective:To observe the histopathological changes in peripheral retinal lesions under intraoperative optical coherence tomography (iOCT).Methods:A retrospective case series study. Eighty-eight patients (194 eyes) who underwent vitreoretinal surgery in the Department of Ophthalmology at the East Ward of the First Affiliated Hospital of Zhengzhou University from October 2021 to May 2022 in 94 eyes were included in the study. Among them, 49 cases were male and 39 cases were female, with the mean age of (50.93±17.55) years. Ninety-four eyes included 32 eyes with retinal detachment, 6 eyes with proliferative diabetic retinopathy, 28 eyes with vitreous hemorrhage, 8 eyes with ocular trauma, 14 eyes with the macular lesion, 1 eye with uveitis, 1 eye with family exudative vitreoretinopathy (FEVR), 1 eye with acute retinal necrosis (ARN), and 3 eyes with lens dislocation. All affected eyes were examined with iOCT during vitreoretinal surgery. The iOCT scanning of the peripheral retina was performed with the help of episcleral pressure. The pre-equatorial and serrated edge anterior and posterior of retinas were scanned according to the characteristics of different fundus diseases. Various abnormal fundus manifestations were recorded.Results:In 94 eyes, 53 eyes (56.38%, 53/94) have different types of retinopathy in the peripheral retina. Of these, 7 eyes (7.45%) have retinal cystoid degeneration; 19 eyes (20.21%) have lattice degeneration; and 8 eyes (8.51%) have pigment degeneration; 9 eyes (9.57%) have pavement-like degeneration; 7 eyes (7.45%) have small occult holes; 1 eye (1.06%) has familial exudative vitreoretinopathy (FEVR) serrated edge "dyke-like" proliferative degeneration; 4 eyes (4.26%) have vitreous and retinopathy adhesions; and one eye (1.06%) has ARN.Conclusion:With clear refractive media, iOCT can provide clear scans of different peripheral retinal lesions.

Objective To preliminarly investigate the application value of Pipeline embolization device ( PED ) in the endovascular interventional treatment of complex intracranial aneurysms. Methods From July 2015 to October 2016, the clinical data of 10 consecutive patients with complex intracranial aneurysm treated with PED at the Department of Neurosurgery, Guangdong General Hospital were enrolled retrospectively. Their surgical modalities,complications,and imaging findings were analyzed. Results Of the 10 patients,7 were females and 3 were males,their age was 32-68 years ( mean age 54 ± 12 years) . There were 8 patients with internal carotid artery aneurysm,1 with middle cerebral artery aneurysm,and 1 with vertebrobasilar artery aneurysm;there were 2 patients with ruptured aneurysm and 8 with unruptured aneurysm;there were 5 patients with saccular aneurysm ( 2 with wide-necked aneu-rysm) ,3 with fusiform aneurysm,2 with dissecting aneurysm;there were 2 patients with medium aneurysm ( diameter>5-15 mm) ,2 with large aneurysm ( diameter>15-25 mm) ,6 with giant aneurysm ( diameter>25 mm) ,and there were 2 patients with recurrent aneurysm. They were all single aneurysms. Three patients were treated with PED in combination with coil embolization,and 7 patients were treated with PED implantation alone. Nine patients were treated with one PED and 1 was treated with 3 PEDs. The immediate postoperative angiography revealed that the contrast agents in the aneurysm cavities were obviously stranded. One patient died after procedure and 1 had quadriplegia after procedure,and the remaining 8 patients had no PED-related complications. The modified Rankin scale score was 0 in 8 cases,5 in 1 case,and 6 in 1 case on the first post-operative day. They were followed up for 14 to 28 months. Conclusions The different types of intracranial aneurysms treated with PED implantation is relatively safe and effective,but there are also some risks of dis-ability and death. Strictly selecting the indications and developing the individualized treatment strategies are needed.

Objective To study the brain functional activation under speech stimulation in presbycusis pa‐tients using blood oxygenation level dependent functional magnetic resonance imaging (BOLD - fMRI) .Methods Eighteen normal hearing young volunteers ,10 normal hearing elderly people and 10 presbycusis patients received fM ‐RI under auditory task .Experimental tasks included monosyllabic verbal stimulating at tone of 1 kHz and sound in‐tensity to 90 dB ± 3 dB(after ambient noise detector Smart Sensor AR844 measurement and calibration) randomly transmitted to left and right ear .Following block design ,each stimulus was repeated twice .The lateralization of brain activation analysis observed changes in hemispheric dominance cases (or ear advantage change) .We observed brain activation analysis and changes of hemispheric lateralization advantage (or ear advantages) .SPM5 software was used to deal with the original pictures in the off - line work station to get fictional maps ,volume and intensity of the acti‐vated brain regions of interest ,and calculate the laterality index (LI) .Results To young people ,regardless of left or right ear stimulation ,the contralateral (region of intrest ,ROI) activation volume and intensity significantly increased compared to ipsilateral ,appearing contralateral hemispheric dominance ,and laterality index were - 0 .58 (left ear stimulation) and 0 .37 (right ear stimulation) .Compared to young people ,elderly people with normal hearing and presbycusis contralateral hemisphere conduction advantage was significantly reduced under monaural stimulation ,and the laterality indexes were - 0 .24 ,0 .28 (the aged group) ,- 0 .18 ,0 .25 (presbycusis group) .Young people received the left and the right ear auditory task respectively ,and the ratio of the total volume of bilateral ROI activation was 1 :2 .06 ,appearing to the right ear advantage (left brain dominance) .While the aged and presbycusis group manifes‐ted as right ear advantage decreased (left ear advantage enhanced) ,whose the total volume ratio was 1 :1 .51 for the old normal subjects and 1 :1 .61 for the hearing impaired seniors .Conclusion Auditory verbal tasks activated brain regions in the superior temporal gyrus and middle temporal gyrus were most obvious .Aging may cause these brain regions to be activated weaker ,appearing to the trend of contralateral hemisphere .The aging and deafness lead to the cortical reorganization .This may be one of the reasons for the declined speech recognition .

Objective To compare DHS(dynamic hip screw )with PFNA(proximal femoral nail antirotation) treatment for intertrochanteric fractures and to analyze their postoperative complications .Methods A total of 107 patients with inter-trochanteric fractures were treated with DHS and PFNA fixation respectively .The type of fracture , postoperative complica-tions and overall efficacy were compared .Results After the follow-up of 28(24 to 36) months.DHS group had a higher overall incidence of postoperative complications than the PFNA group and the difference was statistically significant ( P<0.05).Conclusion In order to reduce the intertrochanteric fracture fixation complications , the type of fracture, osteoporo-sis and biomechanical fixation characteristics need to be considered when selecting surgical procedures .Postoperative func-tional rehabilitation is to be improved .The curative effect of PFNA is better than that of DHS .

Objective To investigate the effect of femoral head replacement for the treatment of intertrochanteric frac -tures among elderly patients .Method There were 38 cases that received intertrochanteric fracture hemiarthroplasty and 35 patients were treated with open reduction and dynamic hip screw ( DHS) plate internal fixation .After follow-up, their opera-tion duration,blood loss, postoperative drainage flow , postoperative ambulation time , hospitalization time were compared according to the Harris score to assess the effect of postoperative follow-up.Results After the mean follow-up time of 18 months (12 to 36 months),the hemiarthroplasty group was superior to the open reduction and DHS plate fixation group ,as shown by the earlier postoperative ambulation time , fewer complications , and better fracture reduction , with an excellent rate of 94 .7%.Conclusion For patients with intertrochanteric fractures , hemiarthroplasty surgery is effective and can re-duce the incidence of postoperative complications .

The Hippo pathway plays a crucial role in controlling organ size by inhibiting cell proliferation and promoting cell death. Recent findings implicate that this pathway is involved in the process of intestinal regeneration and tumorigenesis. Here we summarize current studies for the function of the Hippo signaling pathway in intestinal homeostasis, regeneration and tumorigenesis, and the crosstalk between the Hippo signaling pathway and other major signaling pathways, i.e. Wnt, Notch and Jak/Stat signaling pathways in intestinal compartment.
Animals ; Cell Transformation, Neoplastic ; Drosophila ; Drosophila Proteins ; metabolism ; Homeostasis ; Intestinal Mucosa ; metabolism ; Intracellular Signaling Peptides and Proteins ; metabolism ; Nuclear Proteins ; metabolism ; Protein-Serine-Threonine Kinases ; metabolism ; Regeneration ; Signal Transduction

[Objective]To analyze the clinical features of spinal fracture of the injured in Wenchuan Earthquake and to summarize the medical rescue.[Method]The clinical data of 94 injured cases with spinal fracture in the earthquake were collected and analyzed,including the general condition,injury mechanism,associated injuries and the rescue measures.[Result]The incident rate of the male was much higher than that of the female,the incidence of spinal fracture was high in 21~60-years old;the associated injuries were found in 54 cases,taking up 57.4%.The spinal fracture typing showed that 89 cases had flexion-compression fracture and burst fracture,taking up 94.7%.[Conclusion]Earthquakes cause a large amount of the injured with spinal fracture,who are evacuated within a concentrated time,the injuries are severe with many associated injuries.Scientific organization and reasonable division are critical in the immediate medical rescue of the injured in large quantity within the shortest time.