OBJECTIVE To prepare zeolite imidazole framework （ZIF）-8 nanoparticles （NPs） loaded with temozolomide （TMZ） （abbreviated as TMZ@ZIF-8 NPs） drug delivery system， thus increasing drug enrichment and anti-glioma effects in lesions. METHODS After preparing ZIF-8 NPs using the room temperature solution reaction method， the impregnation method was used to prepare TMZ@ZIF-8 NPs drug delivery system. Characterization was carried out using transmission electron microscopy， laser particle size， and Fourier transform infrared spectroscopy， and dissolution and anti-tumor activity experiments in vitro and in vivo were conducted. RESULTS TMZ@ZIF-8 NPs were successfully prepared with the particle size of （126.23±7.92） nm， drug loading amount of （28.79±1.26）%， and 72 h cumulative dissolution rate of （72.36±3.62）%. The results of in vitro anti-tumor activity experiments showed that the relative cell survival rate of ZIF-8 NPs remained above 90%； the prepared TMZ@ZIF-8 NPs delivery system exhibited superior inhibition， higher uptake capacity， and better promoting apoptosis effects on the growth and proliferation of C6 cells as compared with the free TMZ. The results of in vivo anti-tumor activity experiments showed that ZIF-8 NPs were not enriched in the brain of rats， and the enrichment effect of TMZ in the brain was not significant， while TMZ@ZIF-8 NPs had a significant enrichment effect in the brain. CONCLUSIONS ZIF-8 NPs can effectively load TMZ， and successfully prepared TMZ@ZIF-8 NPs can improve TMZ uptake ability and anti-glioma effect.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Objective:To analyze the clinical phenotype and genetic etiology of a child with Multiple congenital anomalies-hypotonia-seizures syndrome 1 (MCAHS1).Methods:Clinical data of a 2-year-old boy who had presented at the Affiliated Hospital of Qingdao University in March 2023 for "intermittent limb twitching for 2 years" was collected. Peripheral blood samples were collected from the child and his parents for whole-exome sequencing (WES). Candidate variants were verified by Sanger sequencing and bioinformatic analysis based on the guidelines from the American College of Medical Genetics and Genomics (ACMG).Results:The child had manifested with distinctive facial features, limb deformities, hypotonia, motor and intellectual delays, and epileptic seizures. WES revealed that he has harbored compound heterozygous variants of the PIGN gene, namely c. 963G>A (p.Q321=) and c. 994A>T (p.I332F), which were inherited from his phenotypically normal mother and father, respectively. Based on the ACMG guidelines, the c. 963G>A was classified as a pathogenic variant (PVS1+ PM2_Supporting+ PM3), whilst the c. 994A>T was classified as a variant of uncertain significance (PM2_Supporting+ PP3). Conclusion:Above discovery has expanded the mutational spectrum of the PIGN gene variants associated with MCAHS1, which may facilitate delineation of its genotype-phenotype correlation.

Objective:To investigate the interaction between fibroblasts (Fb) and keratinocytes (KC) in the wound edge skin tissue of a diabetic foot patient and the mechanism.Methods:This was an experimental research. The wound edge skin tissue from a diabetic foot patient (male and 33 years old) admitted to the Department of Wound Repair of Liyuan Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology in August 2021 and from an acute foot injury patient (male and 50 years old) admitted to the Department of Hand Surgery of the hospital in September 2021 was collected. The single-cell transcriptome sequencing was performed to analyze the interaction between chemokine ligands of Fb subgroup and chemokine receptors of KC subgroup. The supernatant was collected after human foreskin fibroblast (HFF) was cultured routinely and with high concentration of glucose for 7 days as normal conditioned medium (CM) and high glucose CM, respectively. HaCaT cells were collected and divided into normal CM group cultured with normal CM and high glucose CM group cultured with high glucose CM, the scratch test was performed to calculate the cell migration rates at 24 and 48 h after scratch ( n=3). The content of cytokines in the two kinds of CM was detected by liquid suspension chip ( n=5). HFF was collected and divided into normal group cultured routinely and high glucose group cultured with high concentration of glucose for 7 days, and the mRNA expressions of C-X-C motif chemokine ligand 1 (CXCL1), CXCL2, CXCL8, and CXCL12 were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction ( n=6). HaCaT cells in normal CM group and high glucose CM group were collected to detect the protein expressions of C-X-C motif chemokine receptor 4 (CXCR4) in cells cultured for 48 h by Western blotting ( n=3). HaCaT cells were collected and divided into normal CM group, high glucose CM group, normal CM+CXCL12 group, and high glucose CM+CXCL12 group. The first two groups of cells were treated as before, and the latter two groups of cells were cultured with normal CM and high glucose CM containing recombinant human CXCL12, respectively. Scratch test was performed, and cell migration rates were calculated at 24 and 48 h after scratch ( n=3); the protein expression of CXCR4 in cells cultured for 48 h was detected by Western blotting ( n=3). Results:Compared with those in the wound edge skin tissue of acute foot injury, the interactions between chemokine ligands (CXCL1, CXCL2, CXCL3, CXCL8, and CXCL12) of Fb subgroup and chemokine receptors (CXCR2 and CXCR4) of KC subgroup were significantly weakened in the wound edge skin tissue of diabetic foot. At 24 and 48 h after scratch, the migration rates of HaCaT cells in high glucose CM group were significantly lower than those in normal CM group (with t values of 23.50 and 15.65, respectively, P<0.05). Compared with that in normal CM, the content of CXCL1 in high glucose CM was significantly increased ( P<0.05), and the content of CXCL12 was significantly decreased ( P<0.05). After 7 days of culture, compared with those in normal group, the mRNA expressions of CXCL1, CXCL2, and CXCL8 in HFF in high glucose group were significantly increased (with t values of 4.25, 4.98, and 10.04, respectively, P<0.05), while the mRNA expression of CXCL12 was significantly decreased ( t=4.10, P<0.05). After 48 h of culture, the CXCR4 protein expression in HaCaT cells in high glucose CM group was significantly lower than that in normal CM group ( t= 5.13, P<0.05). At 24 and 48 h after scratch, the migration rates of HaCaT cells in high glucose CM group were significantly lower than those in normal CM group and high glucose CM+CXCL12 group (with P values all <0.05); at 24 h after scratch, the migration rate of HaCaT cells in normal CM+CXCL12 group was significantly lower than that in normal CM group ( P<0.05); at 48 h after scratch, the migration rate of HaCaT cells in normal CM+CXCL12 group was significantly higher than that in high glucose CM+CXCL12 group ( P<0.05). At 48 h of culture, the CXCR4 protein expression of HaCaT cells in high glucose CM+CXCL12 group was 0.446±0.050, which was significantly higher than 0.247±0.010 in high glucose CM group ( P<0.05) and similar to 0.522±0.082 in normal CM+CXCL12 group ( P>0.05); the CXCR4 protein expression in HaCaT cells in normal CM group was 0.509±0.055, which was significantly higher than that in high glucose CM group ( P<0.05). Conclusions:The interactions between chemokine ligands of Fb subgroup and chemokine receptors of KC subgroup were significantly weakened in the wound edge skin tissue of diabetic foot. High glucose can inhibit CXCL12 secretion of HFF, and the stimulation of its cell culture supernatant can decrease HaCaT cell migration ability and CXCR4 expression. Exogenous CXCL12 protein can increase the CXCR4 protein expression in HaCaT cells and enhance the cell migration ability.

Objective:Intravenous thrombolysis (IVT) in patients with acute ischemic stroke is strongly time-dependent.The purpose of this study was to investigate whether the transfer of ischemic stroke patients to hospital through emergency medical service (EMS) could shorten onset to needle time (ONT),onset to door time (ODT), door to imaging time(DIT), door to needle time(DNT) and improve the clinical outcomes of intravenous thrombolysis patients.Methods:We retrospectively collected the clinical and time data of acute ischemic stroke(AIS) patients who received IVT in the Affiliated Hospital of Qingdao University on Laoshan campus from September 2021 to August 2022 were retrospectively collected. Patients were divided into EMS group and Non-EMS group according to patients whether transferred by ambulance. The baseline characteristics, length of each period and differences in clinical outcome were compared. Good prognosis was defined as modified Rankin Scale score of 0-2 at 3-months.Results:A total of 175 patients aged (66.1 ±12.3) years were selected, including 63 females (36.0%) and 53 patients (30.3%) were transferred by EMS. Compared with the Non-EMS group, the patients in the EMS group were older, the baseline NIHSS score was higher, ODT and ONT were shorter (all P< 0.05), but there were no significant difference in DIT and DNT between the two groups. Binary Logistic regression model showed that after adjusting for age, sex, baseline NIHSS score, bridging therapy, history of atrial fibrillation, history of hypertension, the number of previous diseases and intracranial hemorrhage, EMS was independently associated with good prognosis of patients with acute ischemic stroke [odds ratio ( OR) 0.376, 95% confidence interval ( CI) 0.144~0.890, P=0.027). Conclusion:EMS could improve the clinical outcomes of acute stroke patients by shortening the ODT and ONT in patients with acute ischemic stroke.

Epigallocatechin gallate (EGCG) is a major polyphenol component in green tea. EGCG has high free radical scavenging activity, radiation protection efficiency, and metal-chelating capacity due to its unique structure with hydroxyl groups. EGCG and its derivatives have been reported in various fields. This paper reviews the effects of EGCG, including radiation protection, heavy metal ion adsorption, and promotion of heavy metal ion excretion. EGCG has the potential to be used as an ideal radiation protection agent, heavy metal adsorbent, and even excretion promoting agent.

The condition of patients with severe traumatic brain injury (sTBI) complicated by corona virus 2019 disease (COVID-19) is complex. sTBI can significantly increase the probability of COVID-19 developing into severe or critical stage, while COVID-19 can also increase the surgical risk of sTBI and the severity of postoperative lung lesions. There are many contradictions in the treatment process, which brings difficulties to the clinical treatment of such patients. Up to now, there are few clinical studies and therapeutic norms relevant to sTBI complicated by COVID-19. In order to standardize the clinical treatment of such patients, Critical Care Medicine Branch of China International Exchange and Promotive Association for Medical and Healthcare and Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Chinese expert consensus on clinical treatment of adult patients with severe traumatic brain injury complicated by corona virus infection 2019 ( version 2023) based on the joint prevention and control mechanism scheme of the State Council and domestic and foreign literatures on sTBI and COVID-19 in the past 3 years of the international epidemic. Fifteen recommendations focused on emergency treatment, emergency surgery and comprehensive management were put forward to provide a guidance for the diagnosis and treatment of sTBI complicated by COVID-19.

Traumatic cerebrospinal fluid leakage commonly presents in traumatic brain injury patients, and it may lead to complications such as meningitis, ventriculitis, brain abscess, subdural hematoma or tension pneumocephalus. When misdiagnosed or inappropriately treated, traumatic cerebrospinal fluid leakage may result in severe complications and may be life-threatening. Some traumatic cerebrospinal fluid leakage has concealed manifestations and is prone to misdiagnosis. Due to different sites and mechanisms of trauma and degree of cerebrospinal fluid leak, treatments for traumatic cerebrospinal fluid leakage varies greatly. Hence, the Craniocerebral Trauma Professional Group of Neurosurgery Branch of Chinese Medical Association and the Neurological Injury Professional Group of Trauma Branch of Chinese Medical Association organized relevant experts to formulate the " Chinese expert consensus on the diagnosis and treatment of traumatic cerebrospinal fluid leakage in adults ( version 2023)" based on existing clinical evidence and experience. The consensus consisted of 16 recommendations, covering the leakage diagnosis, localization, treatments, and intracranial infection prevention, so as to standardize the diagnosis and treatment of traumatic cerebrospinal fluid leakage and improve the overall prognosis of the patients.

Objective:To investigate the risk factors related to successful endovascular recanalization for non-acute long segmental occlusion of internal carotid artery and propose a strategy for selecting proper candidates for such procedure.Methods:From January 2018 to October 2022, 120 consecutive patients with non-acute long segmental internal carotid artery occlusion received the first intended endovascular recanalization treatment in the First Affiliated Hospital of Zhengzhou University. Potential variables including epidemiology, symptomatology, angiographic morphology and interventional techniques were retrospectively analyzed. Univariate and multivariate logistic regression analyses were made to investigate the independent risk factors for successful recanalization. Four types were divided according to the existence of tapered stump and ophthalmic artery flow reversion based on DSA images: A: tapered stump (-), ophthalmic artery flow reversion (-); B: tapered stump (-), ophthalmic artery flow reversion (+); C: tapered stump (+), ophthalmic artery reversion (-); D: tapered stump (+), ophthalmic artery (+). Investigation of the relationship between procedure success rate and group dividing was performed.Results:Totally 120 patients were all included. The technical success rate was 75.83% (91/120). The periprocedural complication rate was 9.17% (11/120), including 4 (3.33%) intracranial hemorrhagic events, 1 (0.83%) ischemic stroke event, 1 (0.83%) microcatheter perforation, 3 (2.75%) cavernous carotid fistulas, 2 (1.67%) iatrogenic dissections. None of these complications led to severe neurological damage or death. Through multivariate logistic regression, tapered stump (OR=4.10, 95%CI 1.19-14.16), retrograde filling of ophthalmic artery (OR=3.16, 95%CI 1.13-8.88), only cervical segment occlusion of internal carotid artery (OR=10.78, 95%CI 2.08-55.74) were the independent risk factors associated with higher technical success rate. All cases were divided into A-D four types considering the tapered stump and reversed ophthalmic flow existing or not. Technical success rates in A-D types were 30.00% (3/10), 66.67% (8/12), 70.00% (28/40), 89.66% (52/58) respectively, and the complication rates of the four types were 10.00% (1/10), 8.33% (1/12), 17.50% (7/40), 3.45% (2/58). Multivariate logistic regression showed group pattern was the independent factor on technical success rate (OR=3.72, 95%CI 1.42-9.77).Conclusions:Tapered stump, reversed ophthalmic artery flow and pure extracranial artery occlusion are the independent factors for technical success rate. Group pattern which covered the tapered stump and reversed ophthalmic artery flow is also related to technical success rate. However, the results need further confirmation with the prospective trial and a larger sample.

Carcinoma, Non-Small-Cell Lung/genetics* ; Drug Resistance, Neoplasm/genetics* ; ErbB Receptors/metabolism* ; Genomic Instability ; Humans ; Lung Neoplasms/genetics* ; Neoplasm Proteins/metabolism* ; Protein Kinase Inhibitors/therapeutic use*