[Clinical application of a quantitative method of atlantoaxial reduction angle in basilar invagination].

Objectives: To investigate the clinical application effect of a quantitative method of atlantoaxial reduction angle in basilar invagination. Methods: A retrospective analysis of clinical and radiographic data was conducted of 38 patients with complicated atlantoaxial dislocation and basilar invagination admitted to the Department of Neurosurgery, First Affiliated Hospital of Chongqing Medical University from May 2020 to May 2022. There were 5 males and 33 females, aged (53.5±9.9) years (range: 38 to 80 years). All patients underwent C1-2 interarticular fusion cage implantation+occipital-cervical fixation by pressing rob with the cantilever technique. The atlantoaxial reduction model of previous studies by our team was used to calculate the reduction angles before surgery. Then titanium rods of prebending angle were prepared according to the calculation before the operation. After that quantitative reduction of angle was performed during the operation. The paired t-test was used to compare the difference between the theoretical and actual reset value. Results: The theoretical reduction angle of all patients was (10.62±1.78)° (range: 6.40° to 13.20°), the actual reduction angle was (10.53±1.63)° (range: 6.70° to 13.30°) and there was no statistical difference between them (t=1.688, P=0.100). The theoretical posterior occipitocervical angle after the operation of all patients was (117.37±5.88)° (range: 107.00° to 133.00°), the actual posterior occipitocervical angle after the operation was (118.25±6.77)° (range: 105.40° to 135.80°) and there was no statistical difference between them (t=-0.737, P=0.466). The postoperative follow-up time of the patients was more than 6 months and the symptoms of all patients were relieved. All patients had satisfactory fusion between small joints without incision infection, internal fixation fracture, displacement, atlantoaxial redislocation, and other long-term complications. Conclusion: The quantitative method of atlantoaxial reduction angle in basilar invagination can calculate the theoretical reduction angle of the clivus axis angle and guide the preparation of the pre-bending titanium rod before surgery, so as to realize the quantification of the atlantoaxial reduction angle.

[Mediation effect of inflammatory biomarkers on the association between blood lead levels and blood pressure changes in Chinese adults].

Objective: To investigate the role of inflammatory biomarkers in the relationship between blood lead levels and blood pressure changes. Methods: A total of 9 910 people aged 18-79 years who participated in the China National Human Biomonitoring in 2017-2018 were included in this study. A self-made questionnaire was used to collect demographic characteristics, lifestyle and other information, and the data including height, weight and blood pressure were determined through physical examination. Blood and urinary samples were collected for the detection of blood lead and cadmium levels, urinary arsenic levels, white blood cells, neutrophils, lymphocytes, and hypersensitive C-reactive protein (hs-CRP). Weighted linear regression models were used to evaluate the associations between blood lead, inflammatory biomarkers and blood pressure. Mediation analysis was performed to investigate the role of inflammation in the relationship between blood lead levels and blood pressure changes. Results: The median (Q1, Q3) age of all participants was 45.4 (33.8, 58.4)years, including 4 984 males accounting for 50.3%. Multivariate logistic regression model analysis showed that after adjusting for age, gender, residence area, BMI, education level, smoking and drinking status, family history of hypertension, consumption frequency of rice, vegetables, and red meat, fasting blood glucose, total cholesterol, triglycerides, blood cadmium and urinary arsenic levels, there was a positive association between blood lead levels, inflammatory biomarkers and blood pressure (P<0.05). Each 2.71 µg/L (log-transformed) increase of the lead was associated with a 2.05 (95%CI: 0.58, 3.53) mmHg elevation in systolic blood pressure (SBP), 2.24 (95%CI: 1.34, 3.14) mmHg elevation in diastolic blood pressure (DBP), 0.25 (95%CI: 0.05, 0.46) mg/L elevation in hs-CRP, 0.16 (95%CI: 0.03, 0.29)×109/L elevation in white blood cells, and 0.11 (95%CI: 0.02, 0.21)×109/L elevation in lymphocytes, respectively. Mediation analysis showed that the levels of hs-CRP significantly mediated the association of blood lead with SBP, with a proportion about 3.88% (95%CI: 0.45%, 7.32%). The analysis also found that the levels of hs-CRP and neutrophils significantly mediated the association of blood lead with SBP, with a proportion about 4.10% (95%CI: 1.11%, 7.10%) and 2.42% (95%CI: 0.07%, 4.76%), respectively. Conclusion: This study suggests that inflammatory biomarkers could significantly mediate the association of blood lead levels and blood pressure changes.

[Evaluation the application of intra-operative cell salvage in cesarean section based on multicenter data].

Objective: To investigate the safety, efficacy and application indication of intra-operative cell salvage (IOCS) in cesarean section. Methods: A total of 1 265 pregnant women who received IOCS blood transfusion during cesarean section in 11 tertiary A hospitals from August 2016 to January 2019 were collected and divided into <1 500 ml group (796 cases) and ≥1 500 ml group (469 cases) according to the amount of blood loss during cesarean section. The general clinical data, ultrasonic imaging data, perinatal and puerperium indicators were analyzed retrospectively. The risk factors of intraoperative blood loss ≥1 500 mL using IOCS transfusion were analyzed by logistic multivariate regression. Results: (1) A total of 848 001 ml of blood was recovered and a total of 418 649 ml of blood was transfused in 1 265 pregnant women who received IOCS transfusions, which was equivalent to 23 258 U red blood cell suspension, greatly saving medical resources. The intraoperative blood loss in <1 500 ml group and ≥1 500 ml group was 800 ml (300-1 453 ml) and 2 335 ml (1 500-20 000 ml), respectively. No amniotic fluid embolism, severe adverse reactions, shock and death occurred in the two groups. (3) Multivariate regression analysis showed that age ≥35 years (OR=1.5, 95%CI: 1.1-1.9), prenatal hemoglobin level <110 g/L (OR=1.7, 95%CI: 1.3-2.2), history of uterine surgery (OR=1.8, 95%CI: 1.3-2.6), placenta previa (OR=1.9, 95%CI: 1.1-3.1), placenta accreta (OR=2.6, 95%CI: 1.8-3.9), blood pool in the placenta (OR=1.6, 95%CI: 1.1-2.3), abnormal posterior placenta muscle wall (OR=1.8, 95%CI: 1.2-2.6), placenta projecting to the anterior uterine wall (OR=3.0, 95%CI: 1.3-7.0) were risk factors for blood loss ≥1 500 ml in obstetric transfusion using IOCS technique, with statistical significance (all P<0.05). Conclusion: IOCS is safe and effective in cesarean section, which could save the medical resources and reduces medical expenses, however, it is necessary to strictly master the application indication.

[Association of cadmium internal exposure with chronic kidney disease in Chinese adults].

Objective: To analyze the association of the cadmium internal exposure with chronic kidney disease (CKD) in Chinese adults aged 18 and older. Methods: A total of 9 821 adults aged 18-79 from the China National Human Biomonitoring (CNHBM) from 2017 to 2018 were included. Blood and urine cadmium exposure levels were measured by inductively coupled plasma mass spectrometry (ICP-MS), and urine cadmium levels were adjusted with urine creatinine; CKD were defined by estimated glomerular filtration (eGFR) using the chronic kidney disease epidemiology collaboration (CKD-EPI). Weights were considered due to complex sampling process for in statistical analysis. Logistic regression is used to analyze the association of blood cadmium, urine cadmium, and urine cadmium adjusted with creatinine exposure levels with CKD, and restricted cube spline (RCS) was used to assess the exposure-response curve of blood cadmium, urine cadmium and urine cadmium adjusted with creatinine with CKD. Results: The weighted age was 44.75 and males accounted for 61.1%. The prevalence rate of CKD was 12.7%. The geometric mean values of blood cadmium, urine cadmium, and urine cadmium adjusted with creatinine were 0.96 µg/L, 0.61 µg/L, and 0.58 µg/g. After adjusting for confounding factors, the weighted logistic regression showed that the lowest quintile (Q1) was compared with the odds ratio (OR) of the highest quintile (Q5) of blood cadmium, urine cadmium, and urine cadmium adjusted with creatinine and the 95% confidence interval (CI) was 1.80 (1.02-3.20), 1.77 (0.94-3.31) and 1.94 (1.11-3.37) respectively. In the restricted cubic spline regression model, non-linear association of blood cadmium, urine cadmium, and urine cadmium adjusted with creatinine with CKD were observed after adjusting for related confounding factors (P<0.001, 0.018, 0.031 respectively). The risk of CKD increased with the increment of cadmium exposure without risk threshold, and the exposure response curve was steeper at low cadmium exposure. Conclusions: Among Chinese adults aged 18 and older, cadmium exposure is positively associated with the risk of chronic kidney disease.

[Geometric model of reduction in basilar invagination with atlantoaxial dislocation and its clinical application].

Objectives: To establish a geometric model of the atlantoaxial dislocation and basilar invagination reduction,and examine its value for clinical application. Methods: A retrospective analysis of 35 patients with atlantoaxial dislocation and basilar invagination admitted to the Department of Neurosurgery,First Affiliated Hospital of Chongqing Medical University from May 2018 to May 2020 was conducted.There were 5 males and 30 females,aged (48±15) years(range: 19 to 69 years). The geometric model of the atlantoaxial reduction was established based on the mid-sagittal section of the cervical spine. The relevant data were calculated according to the geometric model before operation,and the fusion cage of the corresponding height was placed into C1-2 facet joint of patient for quantitative reduction. The theoretical reset value, actual reset value, postoperative symptoms and complications were collected. The paired t-test was used to compare the difference between theoretical and actual reset value to verify the reliability of the geometric model. Results: The theoretical vertical reduction distance of all patients was (5.79±2.96) mm(range:1.52 to 10.96 mm),and the actual vertical reduction distance was (7.43±2.96)mm(range: 1.40 to 12.77 mm),and there was no statistical difference between them(t=-1.96,P=0.069).The theoretical reduction angle was (10.80±2.24)°(range: 7.09 to 14.86°), the actual reduction angle was (10.64±7.00)°(range: 3.50 to 20.50°),and there was no statistical difference between them (t=0.09, P=0.933). At 6 months follow-up, 35 patients achieved satisfactory atlanto-axial joint fusion, and the symptoms were relieved. No internal fixation system displacement, fracture, wound infection and other complications occurred. Conclusion: This geometric model can estimate the vertical reduction distance and the reduction angle of the axial before operation,and provide a reference for the height of the fusion cage so as to avoid under or over-reduction.

Cartilaginous endplate avulsion is associated with modic changes and endplate defects, and residual back and leg pain following lumbar discectomy.

OBJECTIVE: While cartilaginous endplate (CEP) avulsion is a common finding in discectomy due to lumbar disc herniation, its roles in residual back and leg pain, associations with Modic changes (MCs) and endplate defects (EPD) remain unknown. DESIGN: Patients with a single-level lumbar disc herniation who underwent endoscopic discectomy were studied. On MR images, the adjacent endplates of the herniated disc were assessed for MCs and EPD. The presence of CEP avulsion was examined under endoscopic and visualized inspection. Back and leg pain were evaluated by a numeric rating scale (NRS) and the Oswestry Disability Index. Associations of CEP avulsion with adjacent MCs, EPD, and residual back and leg pain were examined. In addition, histological features of avulsed CEP were determined using gross staining and immunohistochemical methods. RESULTS: A total of 386 patients were included. CEP avulsion was found in 166 (43%) patients, and adjacent MCs and EPD were observed in 117 (30.3%) and 139 (36%) patients. The presence of CEP avulsion was associated with greater age, adjacent MCs (OR = 2.60, 95%CI [1.61-4.19]) and EPD (OR = 1.63, 95%CI [1.03-2.57]). Among the 187 patients with ≥2 years follow-up, CEP avulsion was associated with residual back pain (OR = 2.49, 95%CI [1.29-4.82]) and leg pain (OR = 2.25, 95%CI [1.04-4.84]). Histologically, the avulsed CEP was characterized by multiple defects, apparent inflammation, and nucleus invasion, as well as the upregulation of IL-1ß, caspase-1, and NLRP3 inflammasome. CONCLUSION: CEP avulsion was associated with MCs, EPD, and residual back and leg pain after discectomy, which may be attributed to NLRP3 inflammasome related inflammations.

Therapeutic effects of chimeric antigen receptor T cells (CAR-T) on relapse/refractory diffuse large B-cell lymphoma (R/R DLBCL): a meta-analysis.

OBJECTIVE: Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma (NHL). This study aimed to systematically evaluate the efficacy of chimeric antigen receptor T cells (CAR-T) in treating relapse/refractory DLBCL (R/R DLBCL) and associated complete-remission rate (CR). MATERIALS AND METHODS: PubMed, Cochrane Library, CNKI, VIP, CBM, and Wanfang databases were searched, and literature was collected up to January 2019. According to inclusion criteria and exclusion criteria, two researchers independently reviewed and screened literature, extracted required data and crossly checked them. This meta-analysis was conducted using RevMan 5.3 software. RESULTS: This study finally included 13 English literatures and 263 cases. There was no heterogeneity among all these studies, therefore, fixed effect model was used. Meta-analysis findings showed that total CR rate of R/R DLBCL treated with CAR-T was 46.8% (95% CI: 0.408-0.533). Subgroup analysis showed that CR rate of CD28 group was slightly higher [52.5%, with 95% confidence interval (CI): 0.441-0.602] compared to that of 4-1BB group (41.5%, with 95% CI: 0.324-0.510). CR rate of CD19 group was slightly higher (49.2%, with 95% CI: 0.429-0.556) compared to that of CD20 group (42.2%, with 95% CI: 0.231-0.639). Funnel chart of total CR rate, co-stimulatory factor, and target antigen demonstrated fundamental symmetry. Moreover, age, HSCT administration, CAR-T cell counts, and drug pre-treatment also affected immunotherapy on CAR-T on R/R DLBCL. CONCLUSIONS: CAR-T treatment for R/R DLBCL demonstrated evident curative effect and high complete remission rate. CAR-T cell immunotherapy would be expected to become mainstream therapy for hematolymph system tumors.

Precise label-free leukocyte subpopulation separation using hybrid acoustic-optical chip.

Leukocyte subpopulations contain crucial physiological information; hence, precise and specific leukocyte separation is very important for leukemia diagnosis and analysis. However, conventional centrifugation and immunofluorescence-based separation methods are inaccurate and inconvenient due to the overlapping cell size and density or complex marking processes. Herein, we report a new label-free technology for precise leukocyte subpopulation separation by synergy of acoustic and optical technologies. Standing surface acoustic wave (SSAW) solved the problem of gentle and precise focusing of cells in optical systems. In addition, SSAW was used for the separation of granulocytes, which have evident size distinction from other components. In case of lymphocytes and monocytes, which have overlap in size/density, optical force could distinguish them accurately based on the RI difference, with the convenience of acoustic pre-focusing. In this experiment, separation of three types of leukocyte subtypes with considerable throughput and purity was conducted, through which we obtained 99% pure lymphocytes, 98% pure monocytes, and 95% pure granulocytes. Experimental results prove that the device has robust ability in separating leukocyte phenotypes and have the advantages of being non-invasive, label-free and precise. In the future, this convenient hybrid method will be a potential powerful tool for auxiliary clinical diagnosis and analysis.

[The study of the rational use of antibiotics after nasal surgery].

Objective:To study whether the antibiotics should be used in the patients with or without chronic nasal sinusitis after the nasal surgery,and how to rationally use it.Method：Study design:prospective stratified randomized controlled study.Patients with sinusitis were divided into three groups.A group was without antibiotics,B group was with standard antibiotics using ,and C group was with prolonged antibiotics using.Patients without sinusitis were divided into D group without antibiotics,E group with standard antibiotics using,and F group with prolonged antibiotics using. Observe the postoperative infection rate in each group and compare them.Result：The infection rates were 3.53%,2.67%,0.00% in A,B and C group, and there was no significant differences between three groups. The infection rates were 1.22%,0.00%,1.39% in D,E and F group,and there was no significant differences between them.Conclusion： There was no influence in patients with or without using antibiotics,standard or prolonged using antibiotics after nasal surgery. Recommend not to use antibiotics after nasal surgery,and appropriately use antibioctics within 48 hours.Prolonged using is not recommended.

[The correlation between normal or abnormal vestibule function and prognosis of the low frequency sudden deafness].

Objective:To study the correlation between prognosis and status of the vestibule functions with the patients of the low frequency sudden deafness (SD). Method:Eighty-eight patients with low frequency SD were enrolled in this study, the cervical vestibular evoked myogenic potential (cVEMP), the ocular VEMP (oVEMP) and caloric test were evaluated. Based upon the results of the test, patients were divided into 4 groups. A group has no abnormal test results, B group has one abnormal test results, C group has two abnormal test results,and D group has three abnormal test results. Calculating and comparing the effective rate and uneffective rate were conducted in every group after treatment. Result:In A group, the effective rate is 27.27%, the uneffective rate is 2.27%. In B group, the effective rate is 36.36%, the uneffective rate is 4.55%.In C group, the effective rate is 9.09%, the uneffective rate is 6.82%. In D group, the effective rate is 0%, the uneffective rate is 13.64%. The difference between effective and uneffective rate was significant in group A, B, and D, while, there was no significant difference in group C. Conclusion:The prognosis of low frenquency SD patients without abnormal test results or only with one abnormal test results is good. While, the prognosis of patients with three abnormal test is bad. The prognosis of patients with two abnormal test is not sure. The vestibule functions test can be used to determine the prognosis of low frequency SD in clinical treatment.

[Autosomal dominant hearing loss resulting from mutation in the GJB2 gene:nonsyndromic presentation in a Chinese family].

Objective:To investigate the genotype, phenotype and genetic features. The mutations in GJB2, GJB3, GJB6, SLC26A4 genes, 12SrRNA and tRNASer(UCN) were tested in a Chinese family with autosomal dominant nonsyndromic hearing loss. Method:Blood samples and clinical data of the proband and her partial family members were collected. DNA was extracted from the blood samples. The GJB2, GJB3, GJB6, SLC26A4 genes, 12SrRNA and tRNASer(UCN) mutations were analyzed by polymerase chain reaction(PCR) and direct sequencing. Result:Heterozygous mutation of GJB2 R75Q was identified in the proband and her mother. No mutation of other testing genes was detected. Conclusion:The R75Q mutation of the GJB2 gene cause autosomal dominant nonsyndromic deafness in the proband and her mother. Children can inherit the R75Q mutation from their parents, so the results of gene testing will be helpful for further guidance of procreation.

[Tympanum meningioma: one case report].

Clinical presatation: right ear tinnitus, hearing loss, headache for 1 year with intermittent vertigo for 9 months. Specialized examination: right ear tympanum hyperemia and edema, right ear severe conduction deafness, left ear mild hearing loss. The average threshold: right ear 65 dB, the left ear 35 dB. Imaging examination: CT showed the soft tissue density mass in the right ear tympanum, part of the ear bone obscurity, superior wall of the tympanic cavity attenuation, tympanic sinus entry is not expanding. Imaging diagnosis: chronic otitis media with cholesteatoma formation. Postoperative diagnosis: meningioma.

Joint inference on HIV viral dynamics and immune suppression in presence of measurement errors.

In an attempt to provide a tool to assess antiretroviral therapy and to monitor disease progression, this article studies association of human immunodeficiency virus (HIV) viral suppression and immune restoration. The data from a recent acquired immune deficiency syndrome (AIDS) study are used for illustration. We jointly model HIV viral dynamics and time to decrease in CD4/CD8 ratio in the presence of CD4 process with measurement errors, and estimate the model parameters simultaneously via a method based on a Laplace approximation and the commonly used Monte Carlo EM algorithm. The approaches and many of the points presented apply generally.

The distal cytoplasmic domain of the erythropoietin receptor induces granulocytic differentiation in 32D cells.

The role of hematopoietic growth factors in lineage commitment and differentiation is unclear. We present evidence that heterologous expression of an erythroid specific receptor allows granulocytic differentiation of a myeloid cell line. We have previously characterized a truncation mutant of the erythropoietin receptor (EpoR), which is associated with familial erythrocytosis (Blood 89:4628, 1997). This truncated EpoR lacks the distal 70 amino acids of the cytoplasmic domain. To study the functional role of this distal receptor domain, 32D cells, a murine interleukin-3 (IL-3)-dependent myeloid line, were transfected with the wild-type EpoR (32D/EpoR WT) or the truncated EpoR (32D/EpoR FE). 32D cells expressing either the full-length or truncated EpoR display equivalent proliferative rates in saturating concentrations of Epo. There is a dramatic difference in maturational phenotype between the two cell lines, however. The 32D/EpoR FE cells and mock transfected 32D cells have an immature, monoblastic morphology and do not express the primary granule protein myeloperoxidase. The 32D/EpoR WT cells, on the other hand, demonstrate granulocytic differentiation with profuse granulation, mature, clumped chromatin, and myeloperoxidase expression. There is no evidence of erythroid differentiation in 32D cells transfected with either the full-length or truncated EpoR. Treatment of the cells with the specific Jak2 inhibitor tyrphostin AG 490 inhibits myeloid differentiation driven by the distal EpoR. We conclude that: (1) the distal cytoplasmic domain of the EpoR is able to induce a specific myeloid differentiation signal distinct from mitogenic signaling, and (2) these data extend to myelopoiesis the growing body of evidence that the cellular milieu, not the specific cytokine receptor, determines the specificity of differentiation after cytokine receptor activation.

Plasma membrane calcium ATPase in synaptic terminals of chick Edinger-Westphal neurons.

The plasma membrane calcium ATPase pump (PMCA) is one of two major mechanisms known to be involved in extruding calcium from cells. The monoclonal antibody 5F10 was used to examine the distribution of PMCA in chick Edinger-Westphal neurons, a population of cholinergic preganglionic neurons whose cells bodies reside in the Edinger-Westphal nucleus in the brainstem and whose axons form synaptic terminals on parasympathetic neurons in the ciliary ganglion. Definitive PMCA immunoreactivity was undetectable in Edinger-Westphal cell bodies in the brainstem. In contrast, immunoreactivity for PMCA was robust in ciliary ganglia and resembled patterns of immunoreactivity for the synaptic vesicle antigen SV-2, suggesting that PMCA is expressed in Edinger-Westphal synaptic terminals. Moreover, PMCA immunoreactivity co-localized with immunoreactivity for enkephalin and substance P, two neuropeptides known to be expressed in Edinger-Westphal synaptic terminals. Fine structure studies revealed that PMCA immunoreactivity is associated with synaptic vesicles rather than the plasma membrane in Edinger-Westphal terminals. In immunodot assays, synaptic vesicles purified from Torpedo electric organ are also immunoreactive for PMCA as well as SV-2. Torpedo vesicles are negative for the sarcoplasmic/ endoplasmic reticulum ATPase, suggesting that the observed PMCA immunoreactivity is not associated with smooth endoplasmic reticulum. Immunoblot analysis confirmed that 5F10 recognizes a protein with the correct molecular mass for PMCA in tissue homogenates of chick cerebellum, chick ciliary ganglia, and Torpedo synaptic vesicles. These findings describe a previously unrecognized location for PMCA in the membranes of cholinergic synaptic vesicles. Relevance to previous data and possible functions are discussed.

Choice of lasers for laser angioplasty.

Thrombi in test-tube, intraarterial thrombi and pig aorta wall were in vitro irradiated with continuous CO2 laser, short pulsal and ultrashort pulsal YAG laser (with pulse-width of 10 ns and 40 ps, respectively) and their double frequency laser and excimer laser with a wave-length of 308 nm and pulse-width of 20 ns. Their effect of vaporizing and ablating (photodecomposing) thrombi and their thermal injuring effect on adjacent tissues were compared and assessed in order to select optimal laser with little thermal injuring and more rapid vaporizing or ablating thrombi effect for laser angioplasty. The experimental results showed that excimer laser, ultrashort pulsal YAG laser and its double frequency laser, and double frequency laser of short pulsal YAG laser, with laser beam and blood vessel kept in a coaxial position, can effectively vaporize or ablate thrombi without thermal injury to vessel wall. So they may be used for laser angioplasty. Of them, especially, excimer laser and double frequency laser of ultrashort pulsal YAG laser have short wave-length and high peak power, and more effectively ablate thrombi than others, so they proved to be optimal lasers for laser angioplasty.