BACKGROUND:Cervical rotation-traction manipulation is effective and safe in the treatment of cervical spondylotic radiculopathy,and has been widely used in clinical work.However,its effects on the biomechanics of cervical vertebra and intervertebral disc and the area of intervertebral foramen have not been systematically clarified. OBJECTIVE:Based on the finite element analysis technique,a relevant research and analysis were carried out to provide digital evidence for the mechanism of effect of cervical rotation-traction manipulation in the treatment of cervical spondylotic radiculopathy. METHODS:The CT image data of a volunteer with no neck diseases were selected as the finite element model material at its left-handed physiological limit position.The initial construction of the finite element model was completed by Mimics 19.0 software,Geomagic Studio 2013 software,Hypermash 14.0 software,and ANSYS Workbench 2020 R2 software,respectively.Based on the literature,the grid division of cervical structure and the assignment of elastic modulus and elastic coefficient were completed.Based on the previous work of the team,the mechanical effects of cervical rotation-traction manipulation were simulated on the model.Effects of cervical rotation-traction manipulation on the mechanical parameters of each vertebral body and intervertebral disc in C3-T1 segment and on the cervical lateral foramen area were analyzed. RESULTS AND CONCLUSION:(1)During cervical rotation-traction manipulation,the stress of bone structure was significantly higher than that of soft tissue such as intervertebral disc.(2)When operating the technique,the stress at the top of each cervical vertebra was higher,the stress at the bottom was lower,and the stress at the facet joint and transverse process was lower.The stress at the top of the intervertebral disc was lower,the stress at the bottom was higher,but the highest point of the intervertebral disc stress was outside the top.(3)In addition,after loading the lifting force,the projected area of the C6/C7 intervertebral foramen increased significantly compared with that before loading.(4)It is indicated that the cervical rotation-traction manipulation has the mechanical characteristics of changing the stress structure of the cervical spine itself,and can expand the C6/7 intervertebral cervical foramen area on the opposite side of the patient's cervical rotation,so as to achieve the purpose of treating cervical spondylotic radiculopathy.

Intervention in chronically activated microglia-mediated neuroinflammation is a novel approach to treat Alzheimer's disease (AD). The low permeability of the blood‒brain barrier (BBB) and non-selective distribution in the brain severely restrict AD drugs' disease-modifying efficacy. Here, an immunosuppressant TREM2-lowing antisense oligonucleotides (ASOs) and resveratrol co-loaded cationic liposome is developed as an immune reprogramming nanomodulator modified by acid-cleavable BBB-targeting peptide and microglia-targeting peptide (Res@TcMNP/ASO) for AD management. Res@TcMNP/ASO can enter brain endothelial cells via D-T7 peptides. Then D-T7 undergoes an acid-responsive cleavage, facilitating the escape of Res@MNP/ASO from endo/lysosomes to cross the BBB. The detached Res@MNP/ASO specifically targets M1-phenotype microglia via exposed MG1 peptides to prompt the simultaneous delivery of two drugs into activated microglia. This nanomodulator can not only restore the immune function of microglia through TREM2-lowing ASO but also mitigate the immune stimulation to microglia caused by reactive oxygen species (ROS) through resveratrol, thereby synergistically inhibiting the chronic activation of microglia to alleviate neuroinflammation in AD. Our results indicate that this combination treatment can achieve significant behavioral and cognitive improvements in late APP/PS1 mice.

Alzheimer's disease (AD), characterized by β-amyloid (Aβ) aggregation and neuroinflammation, remains a formidable clinical challenge. Herein, we present an innovative nose-to-brain delivery platform utilizing lactoferrin (Lf)-functionalized lipid nanoparticles (LNPs) co-encapsulating α-mangostin (α-M) and β-site APP cleaving enzyme 1 (BACE1) siRNA (siB). This dual-modal therapeutic system synergistically combines the neuroprotective and microglia-reprogramming capabilities of α-M with the transcriptional silencing of BACE1 via siB, thereby simultaneously inhibiting Aβ production and enhancing its clearance. Fabricated via a microfluidic approach, the LNPs exhibited uniform particle size distribution, great encapsulation efficiency, and robust colloidal stability. Upon intranasal administration, Lf-functionalization enabled superior brain-targeting efficacy through receptor-mediated transcytosis. In vitro studies demonstrated that α-M reversed Aβ-induced low-density lipoprotein receptor downregulation, promoting microglial phagocytosis and autophagic degradation of Aβ, while siB effectively suppressed BACE1 expression, abrogating Aβ synthesis. In vivo investigations in APP/PS1 transgenic mice revealed remarkable cognitive recovery, substantial Aβ plaque reduction, and alleviation of neuroinflammation and oxidative stress. This intricately designed LNP system, exploiting a non-invasive and efficient nose-to-brain delivery route, provides a biocompatible, synergistic, and transformative therapeutic strategy for the multifaceted management of AD.

Objective To investigate the risk factors of relapse in patients with ischemic stroke using aspirin for single drug antiplatelet therapy.Methods A retrospective analysis was conducted on 200 patients with mild and medium ischemic stroke after 12 months of single drug treatment with aspirin,and the patients were divided into non-recurrence group and recurrence group according to the recurrence of stroke.Univariate analysis and multivariate logistic regression model were used to explore whether the related indicators were risk factors for recurrence.The ROC curve was used to predict the critical value of risk factors.Results Univariate analysis showed that platelet count,Hcy level and the A allele at rs12041331 site of PEAR1 gene were statistically significant risk factors(P<0.05).Multifactor analysis showed that the independent risk factor for recurrence was homocysteine level[OR = 1.16(1.089-1.240),P<0.001)].The critical value of ROC prediction was 8.35 μmol/L(sensitivity 0.847,specificity 0.532).Conclusions The Hcy level,platelet count and A allele at rs12041331 site of PEAR1 gene are risk factors for recurrence in patients with ischemic stroke treated with aspirin for Single drug antiplatelet therapy.Hcy level is independent risk factor and can be used to predict the risk of recurrence.

Background and purpose: Long non-coding RNA small nucleolar RNA host gene 5 (lncRNA SNHG5) plays a cancer-promoting role in many cancers, however its effect on colorectal cancer (CRC) and its regulatory mechanism are not clear. This study aimed to explore the mechanism of lncRNA SNHG5/miR-26a-5p/metadherin (MTDH) signal axis promoting metastasis of CRC. Methods: The data of The Cancer Genome Atlas (TCGA) database was analyzed, the abnormal expression of lncRNA in CRC was explored and analyzed the survival. Samples of CRC, paracancerous tissues and complete clinical data of patients who underwent surgical resection from October 2020 to October 2021 were collected. The expression levels of SNHG5 and miR-26a-5p in lncRNA were detected by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR), and the expression level of MTDH was detected by immunohistochemistry. The relationship between the relative expression level of lncRNA SNHG5 in CRC and clinicopathological features and survival time was analyzed. The effects of lncRNA SNHG5 on the proliferation, migration and invasion of CRC cells were detected by cell counting kit-8 (CCK-8), clone formation, scratching assays, transwell test and in vivo xenotransplantation. The relationship between CRC cell metastasis, the expression level of epithelial-mesenchymal transition related molecules and lncRNA SNHG5 expression level by Western blot and immunohistochemical detection were explored. The physical interaction between SNHG5 and miR-26a-5p, MTDH and miR-26a-5p was studied by RNA pull-down test, double luciferase reporter gene detection and RNA co-immunoprecipitation. The functional relationship among the three was verified by CCK-8, EdU and transwell experiments. The effect of SNHG5, miR-26a-5p and MTDH expression on migration and invasion related molecules was analyzed by Western blot. Results: The results of TCGA database analysis showed that lncRNA SNHG5 was significantly upregulated in CRC. The results of RTFQ-PCR and immunohistochemistry showed that the levels of lncRNA SNHG5 and MTDH in CRC tissues were significantly upregulated (P＜0.05), the level of miR-26a-5p was decreased (P＜0.05), and the level of MTDH in samples with high expression of SNHG5 was also increased. The expression of lncRNA SNHG5 in CRC tissues with serosa and extraserosal invasion, distant metastasis, lymph node metastasis and TNM stage Ⅲ was significantly higher compared with subserosal invasion, no distant metastasis and lymph node metastasis and TNM stage Ⅰ-Ⅱ (P＜0.05). The results of survival analysis showed that the high expression of lncRNA SNHG5 was significantly correlated with overall survival rate (P＜0.05). Overexpression of lncRNA SNHG5 could enhance the proliferation, clone formation, migration and invasion of CRC cells, promote the growth and lung metastasis of transplanted tumor, increase the relative expression level of Ki-67 proliferation index and vimentin (P＜0.05), and decrease the relative expression level of E-cadherin (P＜0.05). However, the development of CRC cells was inhibited after inhibition of lncRNA SNHG5 expression. RNA pull-down test, double luciferase reporter gene detection and RNA co-immunoprecipitation confirmed the physical interaction between SNHG5 and miR-26a-5p, MTDH and miR-26a-5p. Upregulation of miR-26a-5p or downregulation of MTDH expression in lncRNA SNHG5 overexpressed cells partially reversed the effects of lncRNA SNHG5 on proliferation, migration, invasion and expression of related molecules in CRC cells. Conclusion: LncRNA SNHG5 is upregulated in CRC tissues and cells, and its high expression is related to tumor progression and poor survival. It can be used as a molecular sponge of miR-26a-5p to regulate the expression of MTDH to promote the proliferation and metastasis of SW620 cells.

【Objective】 To develop a new approach for the preparation of 0.7~0.8 hematocrit concentrated washed red blood cells(RBCs) for fetal anemia in utero transfusion and apply it in clinical. 【Methods】 The erythrocyte suspension and frozen stored erythrocytes within expiry date in Guangzhou Blood Center from March 2020 to February 2021 were taken to prepare concentrated washed RBCs. According to the derivation formula, corresponding weight of RBC preservation solution was added to obtain 0.7~0.8 hematocrit concentrated washed RBCs. Routine blood test data were statistically analyzed by single-sample t test, and P<0.05 was considered statistically significant. Qualified Rh-negative/ O-type 0.7~0.8 hematocrit concentrated RBCs within expiry date were used in clinical intrauterine blood transfusion. 【Results】 The hematocrit of concentrated washing RBCs prepared by the new approach could reach 0.7~0.8. The RBCs count (8.389 ±0.808)×1 0¹²/ L and hemoglobin content(233.730±15.498)g/L were higher while the erythrocyte count (0.732±0.469)×10⁹ /L and platelets count(26.000±26.276)×10⁹/L were lower than the normal values of adults. The mean erythrocyte volume(fL), hemoglobin content(pg) and concentration(g/L )were 88.123±6.359, 30.004±2.809 and 339.980±11.865, respectively, which were normal values of adults. Fetal anemia was significantly improved and the prognosis was good after intrauterine blood transfusion. 【Conclusion】 The 0.7~0.8 hematocrit concentrated washed RBCs prepared by the new approach is consistent with the special blood requirements during fetal anaemia transfusion, meets the clinical treatment standards, and can be applied in clinical.

Objective:To evaluate the prognostic factors and the value of definitive pelvic radiotherapy in patients with stage Ⅳ B hematogenous metastatic cervical squamous cell carcinoma. Methods:Clinical data of 80 patients with Ⅳ B stage squamous cell carcinoma admitted to Zhejiang Cancer Hospital from 2006 to 2016 were retrospectively analyzed. The survival analysis was conducted by Kaplan- Meier method. Prognostic factors were analyzed by Cox models. Results:The 1-, 2-and 5-year overall survival (OS) and progression-free survival (PFS) rates were 52.5%, 26.3%, 16.8% and 25%, 13.8%, 8.8%, with a median OS of 13.8 months and a median PFS of 5.6 months, respectively. The most common site of metastasis was bone (51.3%), followed by lung (36.3%) and liver (26.3%). Univariate analysis revealed that chemotherapy combined with definitive pelvic radiotherapy and ≥6 cycles of chemotherapy were positively correlated with OS and PFS, whereas ECOG performance status score of 3-4 and liver metastasis were negatively correlated with OS and PFS. In multivariate analysis, liver metastasis ( HR=2.23, 95% CI: 1.01-4.91, P=0.048) and ECOG performance status score of 3-4( HR=2.01, 95% CI: 1.03-3.91, P=0 0.040) were significantly correlated with poor OS. Subgroup multivariate analysis showed that compared with chemotherapy±palliative radiotherapy, systemic chemotherapy combined with definitive pelvic radiotherapy significantly improved OS ( HR=0.39, 95% CI: 0.18-0.84, P=0.016). Compared with double drugs combined with<4 cycles of chemotherapy, double drugs in combination with ≥4 cycles of chemotherapy significantly improved OS ( HR=0.32, 95% CI: 0.15-0.68, P=0.003). Conclusions:Patients with low ECOG performance status score or liver metastasis obtain poor prognosis. Definitive pelvic radiotherapy combined with chemotherapy can enhance clinical prognosis of patients with Ⅳ B stage hematogenous metastatic cervical squamous cell carcinoma.

Objective:To investigate clinical and histopathological features of congenital melanocytic nevi (CMN) complicated by proliferative nodules (PN) .Methods:Ten patients with clinically and pathologically confirmed CMN complicated by PN were collected from Department of Dermatology, the Fourth Military Medical University from 2015 to 2019, and their clinical and pathological data were analyzed retrospectively.Results:The 10 patients were aged from 2 to 45 years, with an average age of 15 years. Nine patients developed PN in infancy, and 1 in adulthood. The skin lesions were located on the extremities in 4 cases, on the head and face in 3 cases, and on the trunk in 2 cases, and the trunk and extremities were both involved in 1 case. Skin lesions clinically manifested as 1 or more nodules arising in black patches or plaques. Six patients presented with multiple PN, 4 with solitary PN, with the diameter of a single nodule being 0.2-1.5 cm, and only 1 case presented with ulcers. Histopathological examination showed mature melanocytes in the PN, with few mitotic figures, no obvious cytological atypia, and no necrosis. Immunohistochemical study showed that nevus cells diffusely expressed Melan-A, but did not express or partially expressed HMB45, and the Ki67 proliferation index was below 5%.Conclusion:CMN complicated by PN can occur on the extremities, head, face, and trunk, clinically manifesting as solitary or multiple nodules on pre-existing CMN; histopathologically, mature melanocytes can be observed in PN, immunohistochemical staining for HMB45 and Ki67 can facilitate the diagnosis, and its prognosis needs long-term follow-up.

A case of a young male patient,who came to the Second Xiangya Hospital,Central South University because of snoring for 10 years and nocturnal gatism for half month,was analyzed retrospectively.He was diagnosed as obstructive sleep apnea hypopnea syndrome (OSAHS) finally.The patient had been diagnosed and treated as stroke in the local hospital,while urinary and anal incontinence were not relieved.It was a dilemma for him to be properly diagnosed and treated.Polysomnography in our hospital revealed apnea hypopnea index (AHI) at 44.7 events/h,oxygen desaturation index (ODI) at 70.8 events/h and the longest apnea time at 185 seconds while the lowest blood oxygen saturation reduced to 31％.In addition,413 events of apnea accounted for 61.2％ of the sleep time and the minimal heart rate was 23 times/min.The patient was diagnosed as severe OSAHS with hypoxia metabolic brain disease,moderate pulmonary arterial hypertension,secondary polycythemia and obesity hypoventilation syndrome finally.He received the treatment of positive airway pressure non-invasive ventilator with an average pressure at 11.7 cmH2O with reduced AHI and increased blood oxygen saturation.The urinary and anal incontinence disappeared during the first night of treatment and it has been totally resolved so far.We considered that gatism was secondary to OSAHS with severe hypoxia resulted from attenuated regulation of primary defecation in the night.Physicians should pay attention to OSAHS when accepting obese patients with nocturnal incontinence,obvious daytime sleepiness and night snoring.Urinary and anal incontinence could be completely disappeared under therapy of positive airway pressure.

Objective To evaluate the diagnostic value of ultrasound-guided fine needle aspiration cytology(US-FNAC)in the assessment of radiologically detected ovarian neoplasms and retroperitoneal metastatic lymph nodes. Methods FNAC was performed under ultrasound guidance on 126 patients suspected of ovarian neoplasms and retroperitoneal metastatic lymph nodes. Cytologic examination was performed after staining smears with the haematoxylin and eosin method. Clinical data were retrieved from the medical records and all cytological specimens were reviewed. In these cases, the cytologic findings were correlated with histology of the primary tumor and were compared with surgical pathology. Results Satisfactory sampling was obtained in 86.2% of punctures, and cytological diagnosis was made in 85.7% cases. The size of the lymph nodes punctured was less than 20 mm in 93.5% cases, with the sensitivity of 81.6%、86.2%, specificity of 95.8%、100.0%, positive predictive value of 98.3%、100.0%, negative predictive value of 63.9%、33.3%, and accuracy of 85.3%、87.1%. Seven patients presented slight abdominal discomfort, and relieved without clinical treatment. Conclusions The fine needle aspiration technique has excellent positive predictive value and low morbidity. US-FNAC, as the valuable investigation, is not only useful in the diagnosis of ovarian masses and lymph nodes but can also help in choosing appropriate management. From our experience, US-FNAC can be added in follow-up of selected patients in whom the cytological identification of such masses and nodes is significant for the patient′s treatment.