Objective To investigate the role of autophagy in contrast-induced acute kidney injury(CI-AKI)in rats and to explore its possible mechanism.Methods SD rats were randomly divided into control group,acute kid-ney injury model group(intravenous injection of contrast medium ioversol via tail vein;model),rapamycin(RAPA)group and hydroxychloroquine(HCQ)group.Blood urea nitrogen(BUN)and serum creatinine(Scr)con-tents were measured and the potential change foun in renal pathology was detected by HE staining and microscopy.Transmission electron microscopy was used to observe auto-phagy-related changes in ultrastructure.Western blot was used to observe the expression of microtubule-associated protein 1 light chain 3(LC3)Ⅱ/LC3Ⅰ,ubiquitin-binding protein p62 and Histone deacetylase 4(HDAC4).The expression of HDAC4 was also observed by RT-qPCR.Results Compared with control group,the level of BUN,Scr and HDAC4 expression in the model and HCQ group was increased(P＜0.01),the proximal tubules of the kidney were significantly damaged.In the model group,auto-phagososomes and autolysosomes increased,accompanied by an increase of LC3Ⅱ/LC3Ⅰ and a decrease in the p62 level(P＜0.05,P＜0.01);Compared with model group,there were more autophagosomes and autolysosomes were found in RAPA group(P＜0.01),accompanied by increased LC3Ⅱ/LC3Ⅰratio and decrease in the p62 and HDAC4(P＜0.05,P＜0.01).In contrast,the number of autophagy related structures decreased in HCQ group(P＜0.01),accompanied by the simultaneous increase of LC3Ⅱ/LC3Ⅰ,p62 and the increase of HDAC4(P＜0.01).Conclusions Ioversol may induce autophagy activation,while enhancing autophagy by RAPA alleviates CI-AKI induced renal dysfunction.The mechanism is potentially atributed to the regulation of HDAC4.

BACKGROUND:With social progress,the incidence rate of knee osteoarthritis is getting higher and higher in the face of the rapidly developing aging problem in the social population,and the number of total knee replacement operations is gradually increasing. OBJECTIVE:To study the relationship between prosthesis size and stress shielding by improving the tibial prosthesis base. METHODS:A female patient with severe knee osteoarthritis was selected.Based on Mimics,through extracting the bone structure of the knee joint and simulating the total knee replacement surgery,osteotomy,positioning,and implantation operations were carried out to establish the geometric modeling of the total knee replacement prosthesis(including the femoral prosthesis,tibial bracket,and tibial pad),and improve the design of the tibial prosthesis base,analyze the effect of different tibial prosthesis bases on stress shielding of surrounding bone tissue. RESULTS AND CONCLUSION:(1)Compared with single-stem tibial intramedullary stem prosthesis,the design of four-post tibial intramedullary stem prosthesis created a certain degree of stress shielding around the short stem.However,compared with a thicker single long stem,this stress shielding effect was significantly reduced,and the load was evenly distributed among the four short stems,so there was no stress concentration at the bottom of the pile.(2)The design with a rectangular hole in the middle not only provided relatively good stability,but also helped to reduce stress shielding of cancellous bone to a certain extent,with a reduction rate of 77.5%.(3)Compared with a single-stem tibial intramedullary stem prosthesis,both the four-post tibial intramedullary stem prosthesis and the four-post tibial intramedullary stem prosthesis with a hole in the middle have good stability,which can reduce stress shielding to a certain extent without causing stress concentration,providing theoretical guidance for the design of the tibial intramedullary stem.

Objective:To investigate the distribution and primary drainage sites of the venous drainage system in the pedicled nasal septal mucosal flap, as well as to examine protective measures for the venous system of the nasal septal mucosal flap and its application in repairing the nasal skull base through the anatomical study of the nasal septum mucosal venous system in cadavers.Methods:Gross anatomy dissections were performed on 13 sides perfused fresh frozen cadaveric head specimens. The nasal septum mucosal flap was separated along the perichondrium and subperiosteum, then passed across the vomer, anterior wall of sphenoid sinus, clivus, and towards the anterior edge of vertical plate of palatine bone. Detailed documentation, including photographs, was made to record the morphology, distribution and drainage location of veins of the nasal septum mucosal flap and its pedicle, along with number of sphenopalatine veins. Furthermore, venous injuries resulting from obtaining a pedicled nasal septal mucosa flap were observed. From March 2023 to March 2024, a retrospective analysis was conducted on patients with nasopharyngeal lesions who underwent surgical repair using a modified pedicled nasal septum mucosal flap for venous system protection in the ENT institute and Department of Otorhinolaryngology at the Eye & ENT Hospital of Fudan University. The postoperative endoscopy was employed to assess the viability of the mucosal flap.Results:The veins of the nasal septum mucosa were primarily located in the posterior region, including the vomerine region, anterior wall of the sphenoid sinus, clivus region, and posterolateral wall of the nasal cavity, in a reticular pattern. Perforating veins draining into these bony structures could be observed, although their quantity and morphology varied. Notably, no prominent sphenopalatine veins were identified in 10 specimens examined, while 3 specimens exhibited sphenopalatine veins: one with a small single branch and two with venous bundles. Preservation of the nasal septal vein was possible when dissection was limited to the anterior edge of the wing of vomer. A wider range of dissection increased the risk of veinous injury. In cases where only vascular pedicles at the sphenopalatine foramen were preserved, three cadaveric head specimens retained intact sphenopalatine veins, while drainage veins were completely destroyed in ten other specimens. Fifteen patients with unilateral lesions (8 with recurrent nasopharyngeal carcinoma and 7 with nasopharyngeal radionecrosis) were included in this study. The postoperative reconstructions were carried out using contralateral pedicled nasal septal mucosal flaps. The average follow-up time was 7 months (ranging from 3 to 12 months), and all the nasal septal mucosal flaps survived.Conclusions:The primary location of the drainage vein within the nasal septum mucosa is situated in its posterior region, where it penetrates into adjacent bone structures. Very few sphenopalatine veins pass through the sphenopalatine foramen. Extensive dissection of the pedicled nasal septal mucosal flap may potentially impair the venous system and adversely affect flap survival rates, necessitating further clinical exploration.

Objective:Based on the specific cleavage and non-specific "trans-cleavage" activities of the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein(CRISPR/Cas13), we established a visually amplification-free rapid detection technique of 2019-nCoV nucleic acid. This technique is easily processed with a low detection limit and good specificity.Methods:According to the 2019-nCoV gene sequence, specific CRISPR RNAs were screened and designed by bioinformatics analysis, and then synthesized as universal signal-strained RNA transcription targets in vitro to establish and optimize the reaction system. Moreover, the 2019-nCoV pseudoviral nucleic acid was used as a standard substance to evaluate the detection limit. A total of 65 positive samples were collected from various 2019-nCoV variants, while 48 negative samples included other clinically common respiratory pathogens, such as influenza A virus, influenza B virus, human parainfluenza virus, Klebsiella pneumonia, etc. All samples were tested by quantitative PCR (qPCR), digital PCR, and the method established in this study. The sensitivity and specificity of the newly established method were analyzed and evaluated. Results:With the newly established technique, the detection time for 2019-nCoV nucleic acid could be minimized to 6 minutes. In addition, the detection limit was 14 copies/μl when assisted by the displaying instrument, whereas it increased to 28 copies/μl with the naked eye. This technique had a sensitivity and specificity of 98.5% (66/67) and 100% (46/46) respectively, showing no statistically significant difference compared to the gold standard qPCR( P=1). Conclusions:This study has successfully established a CRISPR/Cas13a-based visually rapid detection technique for 2019-nCoV nucleic acid. This technique offers the advantages of a simple process, convenient operation, low environmental operating requirements, a detection limit close to qPCR, and a strong potential for on-site testing applications.

Nasopharyngeal carcinoma (NPC) is a common malignant tumor in China. Radiotherapy is the first-line treatment. After appropriate radiotherapy, about 5%-15% patients experience recurrence. In view of the poor efficacy and high incidence of severe late toxicities associated with re-irradiation, salvage surgery by the transnasal endoscopic approach is recommended for recurrent NPC (rNPC). Compared with re-irradiation, endoscopic surgery can better prolong survival, improve the quality of life, and reduce complications and medical expenses of patients with rNPC. However, the complexity of the nasopharyngeal skull base enhances the difficulty and risk of surgery. Expanding the boundary of surgical resection remains a clinical challenge for otolaryngologists. In this regard, to help more advanced patients with rNPC, the surgical innovative system of NPC needs to be established by multi-disciplinary cooperation, involving skull base anatomy-based investigation, appropriate administration of the internal carotid artery (ICA), repair of skull base defect, and establishment of various types of endoscopic endonasal nasopharyngectomy.

Objective:To investigate the feasibility of endoscopic salvage surgery for patients with rT2 recurrent nasopharyngeal carcinoma (rNPC) and to analyze their prognostic factors.Methods:The clinical data of 33 patients with rT2 rNPC who underwent endoscopic extended nasopharyngectomy in Eye & ENT Hospital Affiliated to Fudan University from January 2015 to July 2020 were analyzed, including 29 males (87.9%) and 4 females (12.1%), aging (51.7±10.6) years. The clinicopathological characteristics of these patients were recorded and analyzed, in terms of gender, sex, alcohol and cigarette use, interval between primary treatment to recurrence, adjuvant therapy, lymph node metastasis, internal carotid artery (ICA) invasion, necrosis, margin and reconstruction materials. Kaplan Meier analysis was used to plot the overall survival rate and progression free survival rate curve, Log-rank test was used to analyze the prognostic factors among patients, and multivariate Cox proportional hazards regression was used to determine the independent risk factors of tumor progression free survival.Results:Among 33 patients with rT2 rNPC, the recurrence interval of 24 patients with rNPC after primary radiotherapy was more than 2 years. A total of 25 patients received primary radiotherapy and adjuvant chemotherapy at the same time. There were 6 cases with cervical lymph node metastasis, 12 cases with ICA invasion, 8 cases with positive surgical margin, 7 cases underwent ICA embolization before operation. A total of 18 cases underwent pedicled tissue flap repairment after operation, including 12 pedicled nasal septal mucosa flaps and 6 temporalis muscle flaps. The median follow-up time was 15 months. Five patients died because of disease progression (in 2 cases), post surgical ICA hemorrhage (in 1 case), liver metastasis (in 1 case) and dysphagia (in 1 case). The 1-year, 2-year and 3-year overall survival rates of all patients were 93.9%, 81.8% and 81.8%, respectively. The 1-year, 2-year and 3-year progression free survival rates were 74.7%, 59.7% and 40.9%, respectively. Log-rank statistical analysis showed that the positive surgical margin ( P=0.060) and recurrence interval ( P=0.151) were possibly related to the prognosis of rT2 rNPC. Multivariate Cox regression analysis showed that the positive surgical margin was an independent risk factor for patients with rT2 rNPC ( P=0.034). Nasopharynx hemorrhage occurred in 4 patients, skull base bone necrosis occurred in 2 patients, trismus occurred in 3 patients, and no obvious brain complications occurred in 7 patients with ICA embolization. Conclusion:Endoscopic salvage surgery for rT2 rNPC is a safe and effective surgical option, but the long-term effect still needs long-term follow-up in bulk cases.

Objective: To discuss the treatment, pathological subtypes and recurrence of sinonasal chondrosarcoma, and to identify the prognostic factors. Methods: Between January 1994 and May 2018, 47 patients with sinonasal chondrosarcoma who were treated in Eye, Ear, Nose and Throat Hospital, Shanghai Medwal College, Fudan University were retrospectively reviewed, including 19 males and 28 females, aging from 7 months to 71 years old, with a median age of 38 years old. The clinical symptoms, location of tumor, surgical method, pathological subtype, recurrence and prognosis were collected and analyzed. Kaplan-Meier method was used to calculate the disease-specific survival rate, disease-free survival rate and draw survival curve. Log Rank was used to analyze the prognostic factors. Cox regression was used for multivariate analysis. Results: Except for one patient who gave up treatment after tumor biopsy, other 46 patients underwent radical resection, including 31 cases of endoscopic resection and 15 cases of extranasal approach resection. Thirty-nine patients were diagnosed as conventional intramedullary chondrosarcoma with pathological grade Ⅰ of 24 cases and grade Ⅱ of 15 cases. Six cases were diagnosed as mesenchymal chondrosarcoma while 2 cases were diagnosed as myxoid chondrosarcoma. During an average follow-up period of 56.1 months (17-156 months), 23 patients had recurrence (54.8%, 23/42), among whom 9 patients had re-operations and 5 patients died. Thirty-seven patients survived, including 25 patients survived without tumors. In addition, 5 patients were lost to follow-up, including the patient who gave up treatment after tumor biopsy. Five-year overall survival rate and disease-free survival rate was 84.7% and 34.3%, respectively. Multivariate analysis showed that invasion of skull base was an independent risk factor affecting disease-free survival rate (95% confidence interval: 1.089-5.825, P=0.031). Conclusions Radical resection is the primary treatment for sinonasal chondrosarcoma. The most common pathological subtype is conventional intramedullary chondrosarcoma. Sinonasal chondrosarcoma has a high local recurrence rate. The long-term prognosis is well after complete excision of the lesion. The most important cause of death is uncontrollable local disease and invasion of adjacent key structures.

Objective:To investigate the regulatory effects of sphingosine kinase-2 (SphK2) on the function of activated astrocytes and the progression of experimental autoimmune encephalomyelitis (EAE) in mice.Methods:Primary mouse astrocytes were isolated from wild-type (WT) C57BL/6 mice and sphk2 gene knock-out ( sphk2 -/-) mice and stimulated in vitro with interleukin 17 (IL-17). Real-time PCR was used to measure the expression of inflammatory cytokines and chemokines at mRNA levels. Western blot and immunofluorescence were used to detect the expression of glial fibrillary acidic protein (GFAP) and the phosphorylation of signal transducer and activator of transcription 3 (p-STAT3). An EAE mouse model was constructed using myelin oligodendrocyte glycoprotein 35-55 (MOG 35-55) polypeptide. Western blot was used to detect the expression of GFAP and p-STAT3 at protein level and real-time PCR was used to detect the expression of inflammatory cytokines and chemokines at mRNA level in spinal cords. Hematoxylin-Eosin (HE) and Luxol fast blue (LFB) staining were used to observe the changes in inflammatory cell infiltration and demyelination in spinal cords. Results:Compared with the WT group, the phosphorylation of STAT3 was obviously reduced in in vitro activated mouse astrocytes of sphk2 -/- mice, and the expression of inflammatory cytokines and chemokines including monocyte chemotactic protein 1 (MCP-1), TNF-α and IL-6 at mRNA level was also significantly decreased. Compared with the WT EAE group, changes in the above-mentioned cytokines and relative proteins in sphk2 -/- EAE mice in vivo were similar to those in vitro. Moreover, inflammatory cell infiltration and demyelination were significantly reduced in spinal cords of sphk2 -/- EAE mice. However, no significant difference in in vitro or in vivo GFAP expression was observed between WT and sphk2 -/- mice. Conclusions:SphK2 might regulate the function of reactive astrocytes through STAT3 molecular pathway, thereby regulating the production of inflammatory cytokines and chemokines and participating in the pathological process of EAE.

Objective To evaluate the effect of enhanced recovery after surgery (ERAS) on immune function and clinical signs in patients with acute abdomen.Methods From March 2016 to March 2017,patients with acute abdominal admitted in the Emergency Care Center of the First Affiliated Hospital of Zhengzhou University were collected and randomized into ERAS group and conventional peri-operative management group (CPM group).In addition to clinical signs (the time of bowel movemtn recovery,the time of first postoperative ingestion and ambulation,hospital stay,complication rates),the celluar immunity (CD4 +,CD8 +,CD4 +/CD8 +) were determined during peri-operation period.Results A cohort of 240 patients were in ERAS group and 192 patients in CPM group.There was no significant difference in general condition between the two groups (P ＞ O.05).On the first day after operation,the levels of CD4 +,CD4 + /CD8 + decreased in both groups (P ＜ 0.05),but the CPM group had lower levels of CD4 +,CD4 +/CD8 +than the ERAS groups.On the 3rd and 7th days after surgery,the ERAS groups had higer levels of CD4+,CD4+/CD8+ than the CPM groups,(the levels of CD4+,CD4+/CD8+ recovery on the 3rd and 7th day after operation,and the ERAS group was significantly better than the CPM group) (P ＜ 0.05).Compared with CPM group,the recovery of bowel movement appeared earlier after operation in ERAS group with sooner resuming ingestion and ambulation after operation,shorter hospital stay,and lower WHO pain rating scale and complication rates (P ＜ O.05).Conclusions ERAS for patients with acute abdomen can alleviate postoperative suppression of immunity,preserving immune function intact and accelerating postoperative rehabilitation.

Objective To evaluate perioperative nutritional support for patients with acute abdomen in enhanced recovery after surgery (ERAS) programme.Methods A total of 490 patients with acute abdominal disease were collected,287 in ERAS group and 203 in conservative perioperative management (CPM) group.Biochemical and clinical markers of the 2 groups were compared.Results ERAS group had higher plasma albumin level,quicker bowel function recovery,lower postoperative complications,shorter hospital stay,and a lower WHO pain rating scale (all P ＜ 0.05).Conclusion With perioperative nutritional support,ERAS programme can accelerate recovery after emergency surgery,reduce the rate of overall complications,promote bowel function recovery,and decrease morbidity in the perioperative period for patients with acute abdominal disease.