Mitochondrial dysfunction in chondrocytes is a key pathogenic factor in osteoarthritis (OA), but directly modulating mitochondria in vivo remains a significant challenge. This study is the first to verify a correlation between mitochondrial dysfunction and the downregulation of the FOXO3 gene in the cartilage of OA patients, highlighting the potential for regulating mitophagy via FOXO3 gene modulation to alleviate OA. Consequently, we developed a chondrocyte-targeting CRISPR/Cas9-based FOXO3 gene-editing tool (FoxO3) and integrated it within a nanoengineered 'truck' (NETT, FoxO3-NETT). This was further encapsulated in injectable hydrogel microspheres (FoxO3-NETT@SMs) to harness the antioxidant properties of sodium alginate and the enhanced lubrication of hybrid exosomes. Collectively, these FoxO3-NETT@SMs successfully activate mitophagy and rebalance mitochondrial function in OA chondrocytes through the Foxo3 gene-modulated PINK1/Parkin pathway. As a result, FoxO3-NETT@SMs stimulate chondrocytes proliferation, migration, and ECM production in vitro, and effectively alleviate OA progression in vivo, demonstrating significant potential for clinical applications.

The Flash radiotherapy(Flash-RT),which is the key breakthrough in the basic field of radiotherapy technique,which is expected to cause a new major transformation in the field of radiotherapy.In this paper,we reviewed the latest research advances of the application and the mechanism exploration of Flash-RT in tumor treatment.Current studies have found that both the Flash-RT with electron beams and photon and the Flash-RT with proton can reduce injury of normal tissue than radiotherapy with conventional dose-rate,but the relevant mechanisms are not yet clearly understood,which includes but not limited to oxygen depletion,DNA damage,cellular senescence,apoptosis and immune response.The difference of Flash-RT injury between tumor tissue and normal tissue further reduces the limitations of radiotherapy,and reduces the adverse reaction and complication compared with conventional radiotherapy,which has wide application prospects.

Recurrent ulcerative colitis is a difficult point in clinical treatment.Its TCM property is deficiency in nature and excess in superficiality.Deficiency of spleen yang for a long time will affect the kidney;if Taiyang and Shaoyin meridians are attacked for a long time,Jueyin will be involved.San yin diseases will occur,and yang qi will be severely injured;dampness and heat,turbid poison,cold coagulation,food stagnation and other pathogenic factors invade and attack from outside to inside,lie down in the intestinal collaterals,remove heat by stasis,fumigate the lipid membrane and form internal ulcers.Deficiency of healthy qi,weakness and sores are the origin of the disease,stagnation of intestinal collaterals is the superficiality of the disease,and"stasis"as the main pathological factor carries out the disease from beginning to end.According to the idea of supporting sores and removing blood stasis,the self-made Xiaoyong Yukui Decoction can support sores to generate new ones,remove blood stasis and eliminate stagnation,and help regulate cold and heat,so as to strengthen the health and reduce toxin,remove blood stasis and unblock collaterals,so that the pathogenic factors can be removed and health can be restored,and the internal ulcer can heal,achieving good clinical efficacy in treating recurrent ulcerative colitis.

Objective:To develop the Economic Toxicity Scale for Kidney Transplantation Patients, and to test the reliability and validity of the scale.Methods:Drawing upon Coleman′s social capital theory and the six subfields associated with economic toxicity put forward by European scholars, the initial version of the scale was developed via expert correspondence consultation and a preliminary survey. This was accomplished by building upon existing literature and conducting semi-structured interviews. A total of 261 cases of kidney transplantation patients from March to October 2022 admitted to the First Affiliated Hospital of Shandong First Medical University were investigated for reliability and validity test.Results:The Economic Toxicity Scale for Kidney Transplantation Patients included 6 dimensions, 31 entries. The total scale had a Cronbach alpha coefficient of 0.910 and the subscale had Cronbach alpha coefficient ranging from 0.798 to 0.943. The retest reliability coefficient for the total scale was 0.948, while the six dimensions ranged from 0.732 to 0.942.Conclusions:The scale demonstrates strong reliability and validity, making it a reliable tool for objectively evaluating the economic toxicity of kidney transplantation patients.

To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.

Objective:To simulate the neuroendoscopy assisted contralateral cervical 7 (C 7) nerve transfer via prespinal route and measure its relevant anatomical landmarks to explore the clinical feasibility and efficacy of this surgical approach for central upper limb spastic paralysis. Methods:(1) Six fresh cadaver specimens of the head and neck were obtained. Linear incisions of approximately 5 cm were made above the midpoint of the bilateral clavicles to simulate neuroendoscopy assisted contralateral C 7 nerve transfer via prespinal route. With the superior margin of midpoint of the clavicle as central point, distance to the distal bifurcation of the C 7 nerve, distances to the superior or inferior trunks of the proximal brachial plexus nerves, and distances to the exit of the intervertebral foramina of the C 6, C 7, and C 8 nerves were measured. (2) One patient with upper limb spastic paralysis after intracerebral hemorrhage accepted neuroendoscopy assisted contralateral C 7 nerve transfer via prespinal route; the clinical data and efficacy of the patient were retrospectively analyzed. Results:(1) The C 7 nerve, the upper trunk of brachial plexus formed by the C 5 and C 6 nerves and the lower trunk of brachial plexus formed by the C 8 and T 1 nerves could be exposed after neuroendoscopy assisted contralateral C 7 nerve transfer via prespinal route. The distance between the superior margin of midpoint of the clavicle and the distal bifurcation of the C 7 nerve is (2.20±0.11) cm, and its distance to the superior trunk of the proximal brachial plexus is (2.62±0.10) cm, and its distance to the inforior trunk of the proximal brachial plexus nerve is (2.72±0.11) cm. The distance between the superior margin of midpoint of the clavicle and the proximal C 7 nerve (at the exit of the intervertebral foramen) is (7.22±0.15) cm, its distance to the proximal C 6 nerve (at the exit of the intervertebral foramen) is (7.84±0.12) cm, and its distance to the proximal C 8 nerve (at the exit of the intervertebral foramen) is (6.96±0.12) cm. (2) The patient with central upper limb spastic paralysis accepted neuroendoscopy assisted contralateral C 7 nerve transfer via prespinal route successfully, with surgical time lasting for 2 h and bleeding amount of 20 mL. After surgery, the incision healed well, and the patient experienced pain and numbness in the healthy side of the upper limb with subsided symptoms one month after surgery. The spasticity symptoms of the affected upper limb obviously improved after surgery with decreased muscle tone. Follow-up after discharge was performed for 14 months, and the muscle strength of the affected upper limb recovered to level 1 +. Conclusion:Neuroendoscopy assisted contralateral C 7 nerve transfer via prespinal route can expose the proximal and distal C 7 nerves, with minimal invasion; this clinical study has preliminarily confirmed the safety and effectiveness of this transfer via prespinal route in central upper limb spastic paralysis.

Objective:To investigate the surgical outcome and prognostic factors of para-split laminotomy for removal of lumbar spinal canal tumors.Methods:Retrospectively review the clinical data of 35 patients suffering lumbar spinal canal tumors, who underwent the para-split laminotomy for tumor resection in Department of Neurosurgery, Clinical Medical College of Yangzhou University from October 2016 to August 2019, including 16 males and 19 females, and the age was(40.1±10.6)years. Intraoperative blood loss, operation time, tumor resection, tumor pathological results, perioperative complications were observed. Follow-up situations, including tumor recurrence, bony fusion of laminae and spinal stability. Follow-up using outpatient examination and telephone interview was performed by the end of August 2022. The JOA back pain scoring system was used to evaluate the neurological function of the spinal cord, and paired t-test were performed to compare the overall preoperative and postoperative spinal cord neurological function scores. Linear regression and multiple linear regression were used to analyze the prognostic factors. Measurement data of normal distribution were expressed as mean±standard deviation ( ± s), and the comparison before and after operation was performed by paired t-test. Mearsurement data of skewed distribution were expressed as M( Q1, Q3). Count data were expressed as cases. Results:The tumors of 35 patients were resected completely. The median blood loss was 100(75, 140)mL and the average operative duration was (181.1±42.7) min. The postoperative pathological results were as follows: 24 neurilemmomas, 6 meningiomas, 4 ependymomas and 1 neurofibroma. There were no surgery-related complications occurred. The postoperative follow-up ranged from 36 to 69 months, with no tumor recurrence or spinal instability, and bony fusion of laminae seen in some patients on CT imaging. The overall spinal cord neurological function scores of pre and post operation were(19.5±3.4)versus(25.4±2.2), Paired t-test analysis revealed a significant difference between the overall postoperative spinal cord neurological function scores and the preoperative scores, and the postoperative scores were better than the preoperative scores( P<0.05). Multiple linear regression analysis showed a positive correlation between preoperative JOA scores and postoperative JOA scores, and postoperative JOA scores has negative correlation with tumor volume and the age at the time of operation ( P<0.05). Conclusion:Para-split laminotomy with less damage to the posterior spinal structures can effectively improve the neurological function of the spinal cord and protect the stability of the lumbar spine in patients with lumbar spinal canal tumors, and the better the preoperative neurological function of the spinal cord, the better the prognosis of patients, and the smaller the tumor volume, the better the prognosis.

Objective:To detect the expression of has_circ_0001459 in peripheral blood mononuclear cells (PBMCs) of Epstein-Barr virus (EBV)-infected individuals and evaluate its diagnostic value for EBV infection.Methods:The expression profiles of circRNAs in PBMCs of patients with EBV infection were obtained by whole-transcriptome sequencing. Differentially expressed circRNAs with statistical significance were selected based on the criteria of ∣log 2Fold Change∣≥1 and P<0.05. Based on the composition, length and primer specificity, hsa_circ_0001459 with high expression was selected for further research. The relative expression of hsa_circ_0001459 in PBMCs of 60 patients with EBV infection and 45 healthy people was detected by real-time fluorescent quantitative PCR. Receiver operating characteristic (ROC) curve and Kappa analysis were used to analyze the diagnostic value of hsa_circ_0001459 expression for EBV infection. Results:The expression of hsa_circ_0001459 showed an up-regulation trend in patients with EBV infection as compared with that in the healthy people, and the results were consistent with the sequencing results. The area under the ROC curve for screening EBV-infected individuals was 0.83(95%CI: 0.75-0.91) with the sensitivity of 0.80(95%CI: 0.66-0.89) and the specificity of 0.77(95%CI: 0.65-0.86). Kappa analysis indicated that hsa_circ_0001459 was moderately consistent with EBV DNA in the diagnosis of EBV infection (κ=0.51).Conclusions:Hsa_circ_0001459 tended to be highly expressed in PBMCs of EBV-infected individuals, which might be uses as a diagnostic marker for EBV infection.

Objective:To investigate the application of in situ interposition bypass surgery in the treatment of complex intracranial aneurysms.Methods:A retrospective analysis was conducted on the clinical data of 18 patients with complex intracranial aneurysms treated by the in situ interposition bypass at the Department of Neurosurgery of Clinical College of Neurology, Neurosurgery and Neurorehabilitation, Tianjin Medical University from July 2015 to September 2022. Fourteen aneurysms were found being located in the middle cerebral artery(MCA), 2 in anterior cerebral artery(ACA), 1 in posterior inferior cerebellar artery(PICA) and 1 in posterior cerebral artery(PCA). Fourteen bypass surgery were with radial artery(RA) vessel grafts, 3 with superficial temporal artery(STA) vessel grafts and 1 with occipital artery(OA) vessel graft. All patients underwent a surgical procedure of in situ interposition bypass with end-to-end anastomosis after resection of the aneurysms. I-type grafts were applied in 13 bypasses, V-type grafts in 3 bypasses, and Y-type grafts in 2 bypasses. All patients had undergone postoperative Digital subtraction angiography(DSA) or CTA reviews. Glasgow Outcome Scale(GOS) was used to assess postoperative outcome. Scheduled postoperative follow-ups were conducted on all patients.Results:Two patients suffered hemiplegia after surgery. One patient had transient aphasia and it recovered in 3 months. No new neurological dysfunction was observed in the rest of patients. Postoperative DSAs showed good patency of the anastomoses and grafted vessels, except one anastomosis that had a severe stenosis, and no aneurysm was shown. The follow-ups lasted for 3 to 89 months and no recurrence of aneurysm was observed. Sixteen patients achieved GOS score 5 and 2 with GOS score 3.Conclusion:In situ interposition bypass surgery is a safe and effective procedure for the treatment of complex intracranial aneurysms.

Objective:To understand the correlation of different ultrasound characteristics with thyroid cancer, and evaluate the effect and safety of different surgical strategies in pathological suspected cancer and highly suspected cancer by pure ultrasound.Methods:The clinical data of 679 patients (787 thyroid nodules) underwent thyroid surgery from August 2016 to December 2019 in Beijing Daxing District People′s Hospital were retrospectively analyzed, including ultrasound characteristics (echo, margin, form, ratio of tall to wide, calcification), surgery data (operation time, surgical strategies, whether the second surgery), recovery process (whether combined with secondary injury, including hoarse voice and choking on drinking water; drainage tube retention time and postoperative drainage), pathological examination results (pathological types, whether included parathyroid gland in the submitted specimen and whether lymph node metastasis). The effect and safety were compared between dissection and non-dissection of central group lymph nodes in pathological suspected cancer patients and highly suspected cancer by pure ultrasound patients.Results:Among the 787 thyroid nodules, 316 nodules (40.2%) were malignant nodules, including 308 papillary carcinomas; 471 nodules (59.8%) were benign nodules. The rates of low echo, unclear margin, form irregularity, ratio of tall to wide >1 and microcalcification in malignant nodules were significantly higher than those in benign nodules: 90.5% (286/316) vs. 38.9% (183/471), 52.5% (166/316) vs. 11.5% (54/471), 53.8% (170/316) vs. 11.5% (54/471), 30.4% (96/316) vs. 5.5%(26/471) and 65.5% (207/316) vs. 8.7% (41/471), and there were statistical differences ( P<0.01). Among 26 patients with pathological suspected cancer, there were no statistical difference in operation time, drainage tube retention time, postoperative drainage, surgical complications and paraffin pathology result between patients with dissection of central group lymph nodes (17 cases) and patients without dissection of central group lymph nodes (9 cases) ( P>0.05); the patients with dissection of the central group lymph nodes were all proved to be cancer by paraffin pathology examination. The highly suspected cancer by pure ultrasound was in 57 cases, there were no statistical difference in operation time, drainage tube retention time, postoperative drainage, choking on drinking water or hoarse voice between patients with dissection of central group lymph nodes (23 cases) and patients without that dissection (34 cases) ( P>0.05); the incidence of parathyroid gland in the submitted specimen and malignant rate of paraffin pathology result in patients with dissection of central group lymph nodes were significantly higher than those without that dissection: 39.1% (9/23) vs. 2.9% (1/34) and 30.4% (7/23) vs. 8.8% (3/34), and there were statistical differences ( P<0.01 or <0.05). Conclusions:Thyroid ultrasound characteristics have important predictive value. It is recommended to clean central group lymph node in most cases of pathological suspected cancer; while when highly suspected cancer by pure ultrasound happens, it is recommended to clean lymph node only when lymph node metastasis is highly suspected.