BACKGROUND:The extracellular-regulated protein kinase 5(ERK5)signaling protein is essential for the survival of organisms,and resveratrol can promote osteoblast proliferation through various pathways.However,whether resveratrol can regulate osteoblast function through the ERK5 signaling protein needs further verification. OBJECTIVE:To explore the regulatory effect of ERK5 on the proliferation of MC3T3-E1 cells and related secreted proteins,and to further verify whether resveratrol can complete the above process by activating ERK5. METHODS:Mouse MC3T3-E1 preosteoblasts were treated with complete culture medium,XMD8-92(an ERK5 inhibitor),epidermal growth factor(an ERK5 activator),resveratrol alone,XMD8-92+EGF,and resveratrol+XMD8-92,respectively.Western blot assay was used to detect the expression of ERK5 and p-ERK5 proteins,proliferation-related proteins Cyclin D1,CDK4 and PCNA,and osteoblast-secreted proteins osteoprotegerin and receptor activator of nuclear factor-κB ligand in MC3T3-E1 cells of each group.The fluorescence intensity of ERK5,osteoprotegerin and receptor activator of nuclear factor-κB ligand in each group was detected by cell immunofluorescence staining,and cell proliferation was detected by EdU staining,respectively.The appropriate concentration and time of resveratrol intervention in MC3T3-E1 cells were determined by cell morphology observation and cell counting kit-8 assay. RESULTS AND CONCLUSION:The activation of ERK5 signaling protein could effectively promote the proliferation of MC3T3-E1 cells,up-regulate the osteoprotegerin/receptor activator of nuclear factor-κB ligand ratio.The appropriate concentration and time for resveratrol intervention in MC3T3-E1 cells was 5 μmol/L and 24 hours,respectively.Resveratrol could activate ERK5 signaling protein,thereby promoting osteoblast proliferation and up-regulating the osteoprotegerin/RANKL ratio.All these results indicate that resveratrol can promote the proliferation of MC3T3-E1 cells and up-regulate the osteoprotegerin/RANKL ratio by activating the ERK5 signaling protein.

BACKGROUND:Fluid shear stress plays an important role in osteoblast proliferation and apoptosis.However,whether Caveolin-1 is involved in the process of fluid shear stress-induced proliferation and apoptosis in osteoblasts is unknown. OBJECTIVE:To explore the role of Caveolin-1 in fluid shear stress-regulated osteoblast proliferation and apoptosis. METHODS:The MC3T3-E1 osteoblasts in good growth status were selected and loaded with fluid shear stress at an intensity of 1.2 Pa for different times(0,30,60,90 minutes).The expression of Caveolin-1 protein was observed and conditions with a time of 60 minutes were screened for the experiment.MC3T3-E1 cells were divided into control group,fluid shear stress group,fluid shear stress+pcDNA 3.1 group(control),fluid shear stress+pcDNA Cav-1 group(plasmid overexpression),and intervened with fluid shear stress and overexpression of Cav-1,respectively.The expression of molecules related to proliferation and apoptosis in MC3T3-E1 cells was detected by qRT-PCR and western blot.In addition,the proliferative activity of MC3T3-E1 cells was detected by cell counting kit-8 and EdU assay;and cell apoptosis was detected by Hoechst 33258 and flow cytometry. RESULTS AND CONCLUSION:The expression of Caveolin-1 in MC3T3-E1 cells was significantly down-regulated after loading fluid shear stress,and the expression level was lowest after 60 minutes.Overexpression of Caveolin-1 attenuated the proliferation-promoting and apoptosis-suppressing effects of fluid shear stress in MC3T3-E1 cells.In conclusion,Caveolin-1 has a vital role in fluid shear stress-regulated osteoblast proliferation and apoptosis,which may offer a potential therapeutic strategy for osteoporosis.

The increasing number of pulmonary nodules being detected by computed tomography scans significantly increase the workload of the radiologists for scan interpretation. Limitations of traditional methods for differential diagnosis of pulmonary nodules have been increasingly prominent. Artificial intelligence (AI) has the potential to increase the efficiency of discrimination and invasiveness classification for pulmonary nodules and lead to effective nodule management. Chinese Experts Consensus on Artificial Intelligence Assisted Management for Pulmonary Nodule (2022 Version) has been officially released recently. This article closely follows the context, significance, core implications, and the impact of future AI-assisted management on the diagnosis and treatment of pulmonary nodules. It is hoped that through our joint efforts, we can promote the standardization of management for pulmonary nodules and strive to improve the long-term survival and postoperative life quality of patients with lung cancer.

Cell Nucleus ; Cellular Senescence/genetics* ; CRISPR-Cas Systems/genetics*

Aging poses a major risk factor for cardiovascular diseases, the leading cause of death in the aged population. However, the cell type-specific changes underlying cardiac aging are far from being clear. Here, we performed single-nucleus RNA-sequencing analysis of left ventricles from young and aged cynomolgus monkeys to define cell composition changes and transcriptomic alterations across different cell types associated with age. We found that aged cardiomyocytes underwent a dramatic loss in cell numbers and profound fluctuations in transcriptional profiles. Via transcription regulatory network analysis, we identified FOXP1, a core transcription factor in organ development, as a key downregulated factor in aged cardiomyocytes, concomitant with the dysregulation of FOXP1 target genes associated with heart function and cardiac diseases. Consistently, the deficiency of FOXP1 led to hypertrophic and senescent phenotypes in human embryonic stem cell-derived cardiomyocytes. Altogether, our findings depict the cellular and molecular landscape of ventricular aging at the single-cell resolution, and identify drivers for primate cardiac aging and potential targets for intervention against cardiac aging and associated diseases.
Aged ; Animals ; Humans ; Aging/genetics* ; Forkhead Transcription Factors/metabolism* ; Myocytes, Cardiac/metabolism* ; Primates/metabolism* ; Repressor Proteins/metabolism* ; Transcriptome ; Macaca fascicularis/metabolism*

Objectives:To observe the possibility of enlarging the greater sciatic notch by illium osteotomy through the posterior gluteal approach for reaching the intrapelvic upper sacral plexus as well as the covergence level of sacral plexus,and performing the nerve graft for surgical repairing the sacral plexus ruptured injuries or sacral plexus nerve tumor resection.Methods:The clinical data of 10 patients with sacral plexus injury or sacral plexus nerve tumor underwent the surgical operation via the expanded greater sciatic notch at Department of Hand Surgery,Beijing Jishuitan Hospital from July 2016 to November 2020 were retrospectively analyzed.There were 4 male and 6 female patients,with an age of (38.0±9.3)years (range:26 to 56 years).There were 8 cases with sacral plexus injury at the intrapelvic or covergence level (deep to the piriformis). Out of this 8 cases,4 cases with intrapelvic pan-sacral plexus injury,1 case with upper sacral plexus injury and 3 cases with convergence level pan sacral plexus injury.Another 2 cases were sacral plexus neoplasm.The average time from injury or onset to operation was 10.4 months (range:1.5 to 60.0 months). All cases were performed surgery for reaching the intrapelvic upper sacral plexus as well as the covergence level of sacral plexus with enlarging the greater sciatic notch by illium osteotomy through the posterior gluteal approach.Intraoperation the sacral plexus ruptured injurie was repaired and the sacral plexus nerve tumor was resected.Intraoperative findings,postoperative complications and healing of incision and osteotomy of patients were recorded.Results:All the 10 patients underwent the sacral plexus surgical exploration and cutaneous nerve graft for sacral plexus nerve repairing or neurolysis or neoplasm resection through the posterior gluteal approach successfully.The length and width of illium osteotomy mass were (2.9±0.4)cm (range:2.5 to 3.8 cm) and (2.5±0.5)cm (range:1.5 to 3.4 cm) respectively.The median intraoperative bleeding volume was ( M( Q R))800(800)ml (range:400 to 2 000 ml).There were no complication with major vascular injury and hematoma formation,and all incisions healed.The postoperative follow-up was 29.8 months (range:1.5 to 54.0 months).Nine cases of iliac osteotomy were healed,and 1 case was not healed because the follow-up was only 1.5 months. Conclusions:The intrapelvic upper sacral plexus and the convergence level of sacral plexus deep to the piriformis can be exposed clearly through this posterior gluteal approach via illium osteotomy for enlarging the greater sciatic notch,and there was enough operative space that surgical exploration and nerve graft or nerve transfer or neoplasm resection can be performed.

Objectives:To observe the possibility of enlarging the greater sciatic notch by illium osteotomy through the posterior gluteal approach for reaching the intrapelvic upper sacral plexus as well as the covergence level of sacral plexus,and performing the nerve graft for surgical repairing the sacral plexus ruptured injuries or sacral plexus nerve tumor resection.Methods:The clinical data of 10 patients with sacral plexus injury or sacral plexus nerve tumor underwent the surgical operation via the expanded greater sciatic notch at Department of Hand Surgery,Beijing Jishuitan Hospital from July 2016 to November 2020 were retrospectively analyzed.There were 4 male and 6 female patients,with an age of (38.0±9.3)years (range:26 to 56 years).There were 8 cases with sacral plexus injury at the intrapelvic or covergence level (deep to the piriformis). Out of this 8 cases,4 cases with intrapelvic pan-sacral plexus injury,1 case with upper sacral plexus injury and 3 cases with convergence level pan sacral plexus injury.Another 2 cases were sacral plexus neoplasm.The average time from injury or onset to operation was 10.4 months (range:1.5 to 60.0 months). All cases were performed surgery for reaching the intrapelvic upper sacral plexus as well as the covergence level of sacral plexus with enlarging the greater sciatic notch by illium osteotomy through the posterior gluteal approach.Intraoperation the sacral plexus ruptured injurie was repaired and the sacral plexus nerve tumor was resected.Intraoperative findings,postoperative complications and healing of incision and osteotomy of patients were recorded.Results:All the 10 patients underwent the sacral plexus surgical exploration and cutaneous nerve graft for sacral plexus nerve repairing or neurolysis or neoplasm resection through the posterior gluteal approach successfully.The length and width of illium osteotomy mass were (2.9±0.4)cm (range:2.5 to 3.8 cm) and (2.5±0.5)cm (range:1.5 to 3.4 cm) respectively.The median intraoperative bleeding volume was ( M( Q R))800(800)ml (range:400 to 2 000 ml).There were no complication with major vascular injury and hematoma formation,and all incisions healed.The postoperative follow-up was 29.8 months (range:1.5 to 54.0 months).Nine cases of iliac osteotomy were healed,and 1 case was not healed because the follow-up was only 1.5 months. Conclusions:The intrapelvic upper sacral plexus and the convergence level of sacral plexus deep to the piriformis can be exposed clearly through this posterior gluteal approach via illium osteotomy for enlarging the greater sciatic notch,and there was enough operative space that surgical exploration and nerve graft or nerve transfer or neoplasm resection can be performed.

Objective To investigate the clinical efficacy of percutaneous vertebroplasty (PVP) with bone filling container (BFC) and percutaneous kyphoplasty (PKP) by unilateral puncture approach in the treatment of osteoporotic vertebral compression fractures.Methods A retrospective case control study was conducted on 65 patients (65 vertebral bodies) with osteoporotic vertebral compression fractures (OVCF) who received PVP from March 2015 to March 2017 in Henan Provincial People's Hospital.There were 21 males and 44 females,aged 60-91 years,with an average of 76.2 years.The patients were divided into PVP with BFC group (BFC group) and PKP group treated by unilateral puncture approach.There were 10 males and 23 females in BFC group,with an average age of 75.8 years (range,60-91 years).The injured segments were distributed at T10 in seven patients,T11 in nine,T12 in eight,L1 in five,and L2 in four patients.There were 11 males and 21 females in PKP group,with an average age of 76.7 years (range,60-88 years).The injured segments were distributed at T10 in five patients,T11 in seven,T12 in ten,L1 in eight,and L2 in two patients.The operation time,cement leakage,as well as pain visual analogue score (VAS),modified Oswestry dysfunction index (ODI) and the Cobb angle of the fractured vertebral body at 3 days after operation and 12 months after operation were recorded and compared.Results All operations were completed successfully,without serious complications.The patients were followed up for 16-29 months [(21.2 ± 4.5) months] in BFC group and 15-32 months [(23.8 ± 6.2) months] in PKP group.The operation time was (27.8 ± 3.6) minutes in BFC group and (31.0 ± 5.2) minutes in PKP group (P ＜ 0.05).Postoperative X-ray and CT showed that bone cements leakage occurred in three patients of BFC group (9％) and in ten patients of PKP group (31％) (P ＜0.05).The VAS at 3 days after operation in BFC group and PKP group was (2.3 ± 1.0) points and (2.1 ±0.8)points respectively.The VAS at 12 months after operation in BFC group and PKP group was (0.7 ± 0.7) points and (O.8 ± 0.7) points respectively.The postoperative VAS was significantly decreased compared with the preoperative VAS (P ＜0.05),but there was no significant difference between the two groups (P ＞ 0.05).The modified ODI at 3 days after operation in BFC group and PKP group were (31.5 ± 4.7) ％ and (30.4 ± 5.7) ％,respectively.The modified ODI at 12 months after operation in BFC group and PKP group was (16.7 ±4.9)％ and (15.1 ±5.6)％,respectively.The postoperative ODI were significantly decreased compared with the preoperative ODI(P ＜0.05),but there was no significant difference between the two groups (P ＞ 0.05).The Cobb angle of the fractured vertebral body at 3 days after operation in BFC group and PKP group was (9.2 ± 3.0) ° and (10.0 ±2.9)°,respectively.The Cobb angle of the fractured vertebral body at 12 months after operation was (9.6 ± 2.8)° and (10.3 ± 3.0)°respectively.The postoperative Cobb angle was significantly decreased compared with the preoperative Cobb angle (P ＜ 0.05),but there was no significant difference between the two groups (P ＞ 0.05).Conclusions For OVCF,PVP with BFC by unilateral puncture approach can shorten the operation time and reduce the leakage rate of bone cement.It has similar effects with PKP in pain relief,function improvement of daily life and the correction of fracture vertebral kyphosis.

Objective To evaluate the efficacy of modified posterior unilateral subtotal corpectomy osteotomy correction for old thoracolumbar vertebral fractures combined with kyphosis. Methods A retrospective case series study was conducted to analyze 18 patients with old thoracolumbar vertebral fractures combined with kyphosis admitted to the Henan Provincial People's Hospital from January 2012 to October 2016. There were 10 males and eight females, aged 25-70 years, with an average age of 38. 2 years. The injured segments and osteotomy segments included T11 in one patient, T12 in four, L1 in six, and L2 in seven. Five patients had neurological impairment symptoms classified as grade D according to Frankel's classification. All patients underwent the modified posterior unilateral subtotal corpectomy osteotomy correction. The operation time and intraoperative blood loss were recorded. The visual analogue score (VAS), Oswestry dysfunction index (ODI) and kyphosis Cobb angle were compared before operation, half a year after operation and at the last follow-up. The osteotomy fusion was evaluated by Suk criterion and Frankel grading was used to evaluate the recovery of nerve function. The complications were also recorded. Results All patients were followed up for 12-24 months, with an average of 17. 6 months. The operation time was 160-285 minutes [(190. 0 ± 42. 6) minutes, and the intraoperative blood loss was 500-800 ml [(610. 0 ± 134. 3) ml]. The difference of kyphosis Cobb angle between preoperative [(40.5±9.8)°] and [(5.5 ±1.6)°] at 6 months postoperatively had statistical significance (P <0. 05). Compared with the kyphosis Cobb angle of 6 months postoperatively [(5. 5 ± 1. 6)°], the Cobb angle at the final follow-up [(6. 2 ± 1. 5)°] did not change significantly (P>0. 05). The VAS score and ODI at 6 months after operation and at the final follow-up [(3. 1 ± 1. 3)points,(2. 7 ± 0. 7)points and 7. 5 ± 5. 1, 6. 4 ± 2. 5] were significantly different compared with those before operation [(7. 6 ± 2. 4)points, 68. 7 ± 10. 4] (P<0. 05). Bone cutting surface was healed osseously in all patients. The five patients with preoperative neurological impairment of grade D were assigned with grade E at the last follow up. There were two patients with dural rupture and one with pleural effusion during the operation. No complications such as nerve damage, infection or thrombosis occurred. No loosening, fracture or heterotopic ossification occurred during follow-up. Conclusion For old thoracolumbar vertebral fracture combined with kyphosis, the modified posterior unilateral vertebral column resection through unilateral approach can not only achieve the bone fusion between the injured vertebra and the adjacent vertebral body, but also avoid the shortening of the spine, correcting kyphosis and relieving pain, with low incidence of complications.

Objective To evaluate the pathological stage,the presence of detrusor muscle and the clinical significance for standardized examination of specimens for en bloc transurethral resection technique with Hybrid Knife to treat NMIBC (ERBT) compared with conventional TURBT.Methods This was prospective randomized controlled study.This study was approved by the Ethics Committee of Tongji Hospital,Tongji Medical College of Huazhong University of Science and Technology (TJ-IRB20180604),and patients all signed informed consent.The clinical study registration number of this study:NCT03221062.The margin of the tumor was recognized and marked by with Hybrid Knife (0.5 cm away from the normal mucosa).Then water was injected into the submucosa and form a water pad,with a circular cutting layer by layer (0.5 cm away from the marked position),reaching the detrusor muscle in depth.After complete resection,the tumor was removed by specimen bag.Specimens for ERBT cohort were given standard handling.Resected specimen of ERBT stretched with pins on foam and its margin was stained.The basement of specimen was also stained.Total specimen sectioned into appropriate pieces for histological assessment in the department of pathology.TURBT cohort performed traditional surgical methods and pathological examination.All patients received postoperative intravesical instillation according to their pathology.Imaging and cystoscopy were performed every 3 months.The primary study end-point was the quality of resection,including the pathological stage and the presence of DM.Secondary outcomes were:short-term tumour recurrence rate (18 month),feasibility,and safety.Results From January 2017 to October 2017,109 patients were enrolled.51 patients underwent ERBT,and 58 patients underwent TURBT.The clinical characteristics of the patients in each cohort,such as average age,gender,average BMI,smoking history,the mean number of lesions and tumour size had no significant differences (P ＞ 0.05).The operation of 109 cases was completed successfully.There was no statistical difference between the operative time and the postoperative bladder irrigation time.Major intraoperative or postoperative complications (Clavien ≥ Ⅱ) did not occur in all of the patients.The percentage of T1 staging was higher in the ERBT cohort vs.TURBT cohort [21/51 (41.2％) vs.13/58 (22.4％),P =0.035],of which ERBT cohort accurately detected 9 cases (42.8％) of T1b patients,significantly higher than TURBT cohort (2 cases,15.4％) (P =0.096).All the ERBT samples showed the presence of DM (100.0％),while there was only 77.4％ in TURBT cohort (P ＜ 0.05).Mean follow-up (20.3 ± 3.1) months (ranged from 18 to 24 months).Recurrence rate were 8.9％ (4/45) in ERBT cohort vs.22.2％ (12/54) in TURBT cohort (P=0.059).Conclusions ERBT with Hybrid Knife for treatment NMIBC is a safe,effective,and provides high-quality specimens compared to TURBT.More high-risk NMIBC patients,especially T1 b patients,can be detected obviously by pathologist with the standardized treatment of specimens.