Nanoparticle delivery systems have good application prospects in the field of precision therapy, but the preparation process of nanomaterial has problems such as short in vivo circulation time, easy recognition, and clearance by the immune system in the body. In recent years, biomimetic nanoparticle delivery systems mediated by natural cell membranes have become a research hotspot to address these issues. The natural membrane biomimetic nanoparticle delivery system cleverly integrates the advantages of natural biofilm "autologous" and "artificial" functional carriers by using endogenous cell membranes to modify the surface of nanocarriers, endowing them with characteristics such as tumor targeting, low immunogenicity, and long blood circulation. Currently, biomimetic nanoparticle delivery systems have been used in the treatment of malignant tumors, cardiovascular diseases, bacterial infections, and other diseases. This paper analyzes the development status and current research hotspots of natural cell membrane camouflaged biomimetic nanoparticle delivery systems mainly reviews the latest research progress of red blood cell membrane camouflaged biomimetic nanoparticle delivery systems in the field of disease treatment in recent years. It focuses on exploring the advantages, future development prospects, and limitations of biomimetic nanoparticle delivery systems based on red blood cell membrane camouflage in improving drug delivery, to provide a reference for the in-depth research and development of this system.

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.

Aim Based on the apoptotic pathway mediated by receptor interacting protein kinase(RIP)1-RIP3-mixed spectrum kinase domain like protein(MLKL), to explore the effects of naringenin on ovarian granulosa cell apoptosis in rats with polycystic ovary syndrome(PCOS). Methods SD rats were randomly assigned into normal control group, model group, naringenin group, RIP1 inhibitor(Nec-1)group, RIP1-RIP3-MLKL necrosis signal activator(Z-VAD-fmk)group, naringenin+Z-VAD-fmk group, 15 rats per group. ELISA method was performed to measure the levels of IL-1β and TNF-α in ovarian tissue. HE method was performed to observe the shape of the ovary. Granular cells were isolated from ovarian tissue, and flow cytometry was performed to measure apoptosis rate and necrosis rate. Immunohistochemistry was performed to measure the positive expression of p-RIP1 in ovarian tissue. Western blot was employed to detect the expression of RIP1-RIP3-MLKL pathway. Results RIP1 specific inhibitor Nec-1 and naringenin could block the phosphorylation and activation of RIP1, inhibit the RIP1-RIP3-MLKL signaling pathway, reduce the inflammation level in PCOS rats, and alleviate the necrosis and apoptosis of ovarian granulosa cells(P<0.05). Z-VAD-fmk could promote the activation of RIP1-RIP3-MLKL pathway, aggravate the apoptosis of ovarian granulosa cells, and partially weaken the anti-apoptosis effect of naringenin(P<0.05). Conclusions Naringenin may inhibit the apoptosis of ovarian granulosa cells in PCOS rats by blocking the activation of the necrotic apoptotic pathway mediated by RIP1-RIP3-MLKL.

Objective: To explore the relationship between the ratio of dietary vitamin A (VitA) to body weight and hypertension among children, so as to provide a reference for blood pressure control through dietary nutritional interventions and childhood hypertension prevention. Methods: Utilizing the baseline survey and followup sample data from the Healthy Children Cohort established in urban and rural areas of Chongqing from 2014 to 2019, structured quantitative dietary questionnaire and selfdesigned questionnaire were used to investigate the information of dietary intake and socioeconomic characteristics of 15 279 children, as well as blood pressure, height, weight measurement. The ratio of dietary VitA to body weight was divided into four groups based on quartiles [≤P25(Q1), >P25~P50(Q2), >P50~P75(Q3), >P75(Q4)]. Generalized linear regression models and Logistic regression models were used to analyze the correlation between ratio of dietary VitA to body weight with blood pressure levels and prevalence of hypertension. Results: The results of the 2014 baseline survey indicated that, after adjusting for confounding factors such as demographic indicators and nutritional intake, significant differences were observed in systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) among different groups categorized by the ratio of dietary VitA to body weight (F=157.57, 44.71, 95.92, P<0.01). The baseline ratio of dietary VitA to body weight in children exhibited a negative correlation with DBP, SBP and MAP at baseline and in 2019[baseline: β(95%CI)=-0.65(-0.89--0.42), -0.22(-0.42--0.01), -0.36(-0.56--0.16); 2019: β(95%CI)=-0.77(-1.34--0.19), -0.62(-1.21--0.02), -0.77(-1.34--0.19), P＜0.05]. Compared to Q1 group, the risk of hypertension decreased among children in Q4 at baseline and followup in 2019 [OR(95%CI)=0.63(0.49-0.81), 0.18(0.08-0.42), P<0.01]. Conclusions The ratio of dietary VitA to body weight is significantly negatively correlated with blood pressure levels among children, and dietary VitA deficiency is an independent risk factor for hypertension among children. Measures should be taken to actively adjust childrens dietary nutrition and reduce the risk of childhood hypertension.

Hereditary breast cancer refers to breast cancer with a genetic susceptibility gene.PTEN germline mutations are rare in breast cancer,but patients with PTEN mutations have a high risk of breast cancer.In 2021,A young patient with bilateral breast cancer was admitted to the Obstetrics and Gynecology Hospital,Fudan University.Due to bilateral multiple breast lumps,she underwent Vacuum-Assisted Breast Biopsy,which was pathologically confirmed as right ductal carcinoma in situ,left breast invasive carcinoma.The patient had multiple neoplasms in bilateral axillary region skin,neck skin and bilateral inguinal regiona skin,and the second-generation sequencing results of peripheral blood genes showed PTEN gene mutation.Combined with family history,the patient was diagnosed with Cowden syndrome(CS).Such patients should be paid attention to cancer risk management and family management,so as to attain early diagnosis and treatment.

Objective: To evaluate the efficacy and safety of neoadjuvant chemotherapy combined with programmed death-1 (PD-1) antibody in operable, borderline or potentially resectable locally advanced esophageal squamous cell carcinoma(ESCC) in the real world. Methods: The study retrospectively analyzed 28 patients with operable or potentially resectable locally advanced ESCC patients treated with preoperative chemotherapy combined with PD-1 inhibitor in Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School from April 2020 to March 2021. According to the clinical TNM staging system of the 8th edition of the American Joint Committee on Cancer, there were 1, 15, 10, 1 and 1 case of stage Ⅱ, Ⅲ, ⅣA, ⅣB and unknown stage respectively. The treatment was two cycle of dual drug chemotherapy regimen including taxane plus platinum or fluorouracil combined with PD-1 antibody followed by tumor response assessment and surgery if the patient was eligible for resection. Results: Of the 28 patients, 1, 2, 3 and 4 cycles of chemotherapy combined with PD-1 antibody treatment completed in 1, 21, 5, and 1 patient, respectively. Objective response rate (ORR) was 71.4% (20/28), and disease control rate (DCR) was 100% (28/28). The incidence of adverse events exceeding grade 3 levels was 21.4% (6/28), including 3 neutropenia, 1 leukopenia, 1 thrombocytopenia and 1 immune hepatitis. There was no treatment-related death. Of the 23 patients underwent surgery, R0 resection rate was 87.0% (20/23), 13 patients had down staged to the T1-2N0M0 I stage, the pCR rate was 17.3% (4/23), and the pCR rate of primary tumor was 21.7% (5/23). Four patients received definitive chemoradiotherapy. One patient rejected surgery and other treatment after achieved PR response. Conclusion: Neoadjuvant chemotherapy combined PD-1 inhibitor is safe and has high efficacy in operable, borderline or potentially resectable locally advanced ESCC, and it is a promising regimen.
Humans ; Antibodies/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols ; Carcinoma, Squamous Cell/surgery* ; Cisplatin ; Esophageal Neoplasms/surgery* ; Esophageal Squamous Cell Carcinoma/drug therapy* ; Immune Checkpoint Inhibitors/therapeutic use* ; Neoadjuvant Therapy ; Programmed Cell Death 1 Receptor/therapeutic use* ; Retrospective Studies ; Treatment Outcome

Objective: To identify the risk factors in mortality of pediatric acute respiratory distress syndrome (PARDS) in pediatric intensive care unit (PICU). Methods: Second analysis of the data collected in the "efficacy of pulmonary surfactant (PS) in the treatment of children with moderate to severe PARDS" program. Retrospective case summary of the risk factors of mortality of children with moderate to severe PARDS who admitted in 14 participating tertiary PICU between December 2016 to December 2021. Differences in general condition, underlying diseases, oxygenation index, and mechanical ventilation were compared after the group was divided by survival at PICU discharge. When comparing between groups, the Mann-Whitney U test was used for measurement data, and the chi-square test was used for counting data. Receiver Operating Characteristic (ROC) curves were used to assess the accuracy of oxygen index (OI) in predicting mortality. Multivariate Logistic regression analysis was used to identify the risk factors for mortality. Results: Among 101 children with moderate to severe PARDS, 63 (62.4%) were males, 38 (37.6%) were females, aged (12±8) months. There were 23 cases in the non-survival group and 78 cases in the survival group. The combined rates of underlying diseases (52.2% (12/23) vs. 29.5% (23/78), χ²=4.04, P=0.045) and immune deficiency (30.4% (7/23) vs. 11.5% (9/78), χ²=4.76, P=0.029) in non-survival patients were significantly higher than those in survival patients, while the use of pulmonary surfactant (PS) was significantly lower (8.7% (2/23) vs. 41.0% (32/78), χ²=8.31, P=0.004). No significant differences existed in age, sex, pediatric critical illness score, etiology of PARDS, mechanical ventilation mode and fluid balance within 72 h (all P>0.05). OI on the first day (11.9(8.3, 17.1) vs.15.5(11.7, 23.0)), the second day (10.1(7.6, 16.6) vs.14.8(9.3, 26.2)) and the third day (9.2(6.6, 16.6) vs. 16.7(11.2, 31.4)) after PARDS identified were all higher in non-survival group compared to survival group (Z=-2.70, -2.52, -3.79 respectively, all P<0.05), and the improvement of OI in non-survival group was worse (0.03(-0.32, 0.31) vs. 0.32(-0.02, 0.56), Z=-2.49, P=0.013). ROC curve analysis showed that the OI on the thind day was more appropriate in predicting in-hospital mortality (area under the curve= 0.76, standard error 0.05,95%CI 0.65-0.87,P<0.001). When OI was set at 11.1, the sensitivity was 78.3% (95%CI 58.1%-90.3%), and the specificity was 60.3% (95%CI 49.2%-70.4%). Multivariate Logistic regression analysis showed that after adjusting for age, sex, pediatric critical illness score and fluid load within 72 h, no use of PS (OR=11.26, 95%CI 2.19-57.95, P=0.004), OI value on the third day (OR=7.93, 95%CI 1.51-41.69, P=0.014), and companied with immunodeficiency (OR=4.72, 95%CI 1.17-19.02, P=0.029) were independent risk factors for mortality in children with PARDS. Conclusions: The mortality of patients with moderate to severe PARDS is high, and immunodeficiency, no use of PS and OI on the third day after PARDS identified are the independent risk factors related to mortality. The OI on the third day after PARDS identified could be used to predict mortality.
Female ; Male ; Humans ; Child, Preschool ; Infant ; Child ; Critical Illness ; Pulmonary Surfactants/therapeutic use* ; Retrospective Studies ; Risk Factors ; Respiratory Distress Syndrome/therapy*

To compare the pancreatic proteomics and autophagy between Rehmanniae Radix-and Rehmanniae Radix Praeparata-treated mice with type 2 diabetes mellitus(T2DM). The T2DM mouse model was established by high-fat diet coupled with streptozotocin(STZ, intraperitoneal injection, 100 mg·kg~(-1), once a day for three consecutive days). The mice were then randomly assigned into a control group, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) catalpol groups, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix Praeparata groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) 5-hydroxymethyl furfuraldehyde(5-HMF) groups, and a metformin(250 mg·kg~(-1)) group. In addition, a normal group was also set and each group included 8 mice. The pancreas was collected after four weeks of administration and proteomics tools were employed to study the effects of Rehmanniae Radix and Rehmanniae Radix Praeparata on protein expression in the pancreas of T2DM mice. The expression levels of proteins involved in autophagy, inflammation, and oxidative stress response in the pancreatic tissues of T2DM mice were determined by western blotting, immunohistochemical assay, and transmission electron microscopy. The results showed that the differential proteins between the model group and Rehmanniae Radix/Rehmanniae Radix Prae-parata group were enriched in 7 KEGG pathways, such as autophagy-animal, which indicated that the 7 pathways may be associated with T2DM. Compared with the control group, drug administration significantly up-regulated the expression levels of beclin1 and phosphorylated mammalian target of rapamycin(p-mTOR)/mTOR and down-regulated those of the inflammation indicators, Toll-like receptor-4(TLR4) and Nod-like receptor protein 3(NLRP3), in the pancreas of T2DM mice, and Rehmanniae Radix showed better performance. In addition, the expression levels of inducible nitric oxide synthase(iNOS), nuclear factor erythroid 2-related factor 2(Nrf2), and heine oxygenase-1(HO-1) in the pancreas of T2DM mice were down-regulated after drug administration, and Rehmanniae Radix Praeparata demonstrated better performance. The results indicate that both Rehmanniae Radix and Rehmanniae Radix Praeparata can alleviate the inflammatory symptoms, reduce oxidative stress response, and increase the autophagy level in the pancreas of T2DM mice, while they exert the effect on different autophagy pathways.
Mice ; Animals ; Diabetes Mellitus, Type 2/genetics* ; Streptozocin/pharmacology* ; Diet, High-Fat/adverse effects* ; Proteomics ; Inflammation ; TOR Serine-Threonine Kinases ; Autophagy ; Mammals

Management and treatment of terminal metastatic castration-resistant prostate cancer (mCRPC) remains heavily debated. We sought to investigate the efficacy of programmed cell death 1 (PD-1) inhibitor plus anlotinib as a potential solution for terminal mCRPC and further evaluate the association of genomic characteristics with efficacy outcomes. We conducted a retrospective real-world study of 25 mCRPC patients who received PD-1 inhibitor plus anlotinib after the progression to standard treatments. The clinical information was extracted from the electronic medical records and 22 patients had targeted circulating tumor DNA (ctDNA) next-generation sequencing. Statistical analysis showed that 6 (24.0%) patients experienced prostate-specific antigen (PSA) response and 11 (44.0%) patients experienced PSA reduction. The relationship between ctDNA findings and outcomes was also analyzed. DNA-damage repair (DDR) pathways and homologous recombination repair (HRR) pathway defects indicated a comparatively longer PSA-progression-free survival (PSA-PFS; 2.5 months vs 1.2 months, P = 0.027; 3.3 months vs 1.2 months, P = 0.017; respectively). This study introduces the PD-1 inhibitor plus anlotinib as a late-line therapeutic strategy for terminal mCRPC. PD-1 inhibitor plus anlotinib may be a new treatment choice for terminal mCRPC patients with DDR or HRR pathway defects and requires further investigation.
Male ; Humans ; Prostate-Specific Antigen ; Treatment Outcome ; Prostatic Neoplasms, Castration-Resistant/drug therapy* ; Immune Checkpoint Inhibitors/therapeutic use* ; Retrospective Studies

OBJECTIVE: To investigate whether 3D-printed artificial vertebral body can reduce prosthesis subsidence rate for patients with cervical chordomas, through comparing the rates of prosthesis subsidence between 3D printing artificial vertebral body and titanium mesh for anterior spinal reconstruction after total spondylectomy. METHODS: This was a retrospective analysis of patients who underwent surgical treatment for cervical chordoma at our hospital from March 2005 to September 2019. There were nine patients in the group of 3D artificial vertebral body (3D group), and 15 patients in the group of titanium mesh cage (Mesh group). The patients' characteristics and treatment data were extracted from the medical records, including age, gender, CT hounsfield unit of cervical vertebra and surgical information, such as the surgical segments, time and blood loss of surgery, frequency and degree of prosthesis subsidence after surgery. Radiographic observations of prosthesis subsidence during the follow-up, including X-rays, CT, and magnetic resonance imaging were also collected. SPSS 22.0 was used to analysis the data. RESULTS: There was no significant difference between the two groups in gender, age, CT hounsfield unit, surgical segments, time of surgery, blood loss of posterior surgery and total blood loss. Blood loss of anterior surgery was 700 (300, 825) mL in 3D group and 1 500 (750, 2 800) mL in Mesh group (P < 0.05). The prosthesis subsidence during the follow-up, 3 months after surgery, there was significant difference between the two groups in mild prosthesis subsidence (P < 0.05). The vertebral height of the 3D group decreased less than 1 mm in eight cases (no prosthesis subsidence) and more than 1 mm in one case (mild prosthesis subsidence). The vertebral height of the Mesh group decreased less than 1 mm in five cases (no prosthesis subsidence), and more than 1 mm in eight cases (mild prosthesis subsidence). Two patients did not have X-rays in 3 months after surgery. There was a statistically significant difference between the two groups in the prosthesis subsidence rate at the end of 12 months (P < 0.01). The vertebral height of eight cases in the 3D group decreased less than 1 mm (no prosthesis subsidence) and one case more than 3 mm (severe prosthesis subsidence). Four of the 15 cases in the Mesh group decreased less than 1 mm (no prosthesis subsidence), two cases more than 1 mm (mild prosthesis subsidence), and nine cases more than 3 mm (severe prosthesis subsidence). There was a statistically significant difference between the two groups in the prosthesis subsidence rate at the end of 24 months (P < 0.01). The vertebral height of seven cases in the 3D group decreased less than 1 mm (no prosthesis subsidence), one case more than 3 mm (severe prosthesis subsidence), and one case died with tumor. One case in the Mesh group decreased less than 1 mm (no prosthesis subsidence), one case more than 1 mm (mild prosthesis subsidence), 11 case more than 3 mm (severe prosthesis subsidence), one case died with tumor and one lost the follow-up. Moreover, at the end of 12 months and 24 months, there was significant difference between the two groups in severe prosthesis subsidence rate (P < 0.01). CONCLUSION 3D-printed artificial vertebral body for anterior spinal reconstruction after total spondylectomy for patients with cervical chordoma can provide reliable spinal stability, and reduce the incidence of prosthesis subsidence after 2-year follow-up.
Humans ; Chordoma/surgery* ; Retrospective Studies ; Vertebral Body ; Titanium ; Cervical Vertebrae/surgery* ; Printing, Three-Dimensional ; Spinal Fusion/methods* ; Treatment Outcome