The developmental origins of health and disease and intergenerational inheritance: a scoping review of multigenerational cohort studies.

Epidemiologic research has increasingly acknowledged the importance of developmental origins of health and disease (DOHaD) and suggests that prior exposures can be transferred across generations. Multigenerational cohorts are crucial to verify the intergenerational inheritance among human subjects. We carried out this scoping review aims to summarize multigenerational cohort studies' characteristics, issues, and implications and hence provide evidence to the DOHaD and intergenerational inheritance. We adopted a comprehensive search strategy to identify multigenerational cohorts, searching PubMed, EMBASE, and Web of Science databases from the inception of each dataset to June 20th, 2022, to retrieve relevant articles. After screening, 28 unique multigenerational cohort studies were identified. We classified all studies into four types: population-based cohort extended three-generation cohort, birth cohort extended three-generation cohort, three-generation cohort, and integrated birth and three-generation cohort. Most cohorts (n = 15, 53%) were categorized as birth cohort extended three-generation studies. The sample size of included cohorts varied from 41 to 167,729. The study duration ranged from two years to 31 years. Most cohorts had common exposures, including socioeconomic factors, lifestyle, and grandparents' and parents' health and risk behaviors over the life course. These studies usually investigated intergenerational inheritance of diseases as the outcomes, most frequently, obesity, child health, and cardiovascular diseases. We also found that most multigenerational studies aim to disentangle genetic, lifestyle, and environmental contributions to the DOHaD across generations. We call for more research on large multigenerational well-characterized cohorts, up to four or even more generations, and more studies from low- and middle-income countries.

Will coronal alignment postoperatively be deteriorating in adult spinal deformity after long-fusion surgery?

BACKGROUND: To investigate whether the coronal alignment (CA) will deteriorate, and identify the risk factors for coronal malalignment (CM) developing in adult spinal deformity (ASD) after long-fusion surgery. METHODS: A multi-center retrospective study was performed, which included a total of 161 ASD patients who had undergone the surgical procedure of long-fusion (≥ 5 vertebras) with instrumentations in three medical centers. All of the participants were retrospectively reviewed, and subsequently assigned into the consistency group (C7 plumb line (C7PL) shifting towards the convex side of the main curve), and the opposition group (C7PL shifting towards the concave side). CM was considered if the coronal balance distance (CBD) being over 30 mm. A Kaplan-Meier curve and log-rank test were used to analyze the differences in CM-free survival during follow-up. Multivariate analysis via a Cox proportional hazards test was used to analyze the risk factors. RESULTS: Patients showing CM equaled 35 (21.7%) at the pre-operation, and that increased significantly up to 51 (31.7%) at the final follow-up (P = 0.04). In the consistency group, the incidence of CM at the final follow-up was much higher than that preoperatively (35:16, P = 0.002). CM-free survival time decreased significantly in patients with larger CBD correction, pelvic fixation and more instrumented segments, respectively, during follow-up (P < 0.05, log-rank test). Age ≥ 60 years, the consistency CA, pelvic fixation, CBD-correction ≥ 30 mm and fixed-vertebra ≥ 8 were risk factors for CM happening after surgery using multivariate regression analysis (P < 0.05). CONCLUSIONS: The coronal alignments in ASD patients underwent long-fusion surgeries may deteriorate during follow-up, for which the risk factors include the consistency CA, age ≥ 60, fixed-vertebra ≥ 8, CBD-correction ≥ 30 mm and pelvic fixation.

Iagnosis and treatment of myelitis after lumbar reoperation: A case report.

RATIONALE: At present, acute myelitis (AM) is a great challenge to diagnosis and treatment because of its complicated etiology, critical condition, and poor prognosis, and it is easy to leave different degrees of limb motor dysfunction. The report of this case is helpful to improve the understanding of AM after lumbar surgery, reduce misdiagnosis and provide reference for clinical treatment. PATIENTS CONCERN: This study reported a case of AM after lumbar reoperation. Before the patient was diagnosed as AM, we gave high-dose hormone anti-inflammatory and detumescence symptomatic treatment according to empirical treatment, and the effect was ideal and rehabilitation treatment was actively carried out at the right time. After 10 months of follow-up, the patient recovered well. DIAGNOSIS: Because lumbar surgery is a contraindication of lumbar puncture, the patient's diagnosis was confirmed by thoracic magnetic resonance imaging. Magnetic resonance imaging of thoracic vertebra on the 17th day after lumbar operation showed that small round T1W1 signal, slightly higher T2W1 signal and T2-fat suppression imaging equal signal were seen in the horizontal spinal cord of thoracic vertebra 10. INTERVENTION: According to the empirical treatment, patients have been given high-dose hormone therapy after operation, and comprehensive treatment such as comprehensive training of paraplegic limbs, joint loosening training, electric massage and other rehabilitation training will be carried out when the general condition of patients improves. OUTCOMES: After 10 months of follow-up, there were no major sequelae such as limb paralysis. CONCLUSION: Due to the rarity of AM in clinical work, it is easy for doctors to ignore the disease and miss the best treatment stage, which will lead to serious sequelae.

Scalable synthesis of N/S co-doped hard carbon microspheres as a high-performance anode material for sodium-ion batteries.

Hard carbon is a promising anode material for sodium-ion batteries (SIBs) due to its abundance. However, it exhibits low reversible capacity and slow kinetics if inappropriate microstructural features are developed during synthesis. Herein, N/S co-doped phenolic resin-based hard carbon microspheres are prepared by a scalable strategy, and the electrochemical performance is assessed both in half cells and full cells. We demonstrate that the expanded interlayer spacing, the increased active sites, and the enhanced capacitive behavior result in the enhanced reversible capacity and promoted kinetics for Na+storage. The sample with appropriate doping amount exhibits an initial charge capacity of 536.8 mAh g-1at 50 mA g-1and maintains 445.9 mAh g-1after 1000 cycles at a current density of 1 A g-1in a Na-metal half cell. Coupled with a carbon-coated Na4Fe3(PO4)2P2O7(NFPP) cathode, the full cell exhibits a capacity of 92.5 mAh g-1after 90 cycles, with a capacity retention of 91.6%. This work provides a facile and scalable method for synthesizing high-performance hard carbon anode materials for SIBs.

How does the correction in lumbar lordosis affect the spinopelvic realignments in degenerative lumbar scoliosis underwent scoliosis surgery?

BACKGROUND: To evaluate the effects of correction in lumbar lordosis (LL) that have on full-body realignments in patients with degenerative lumbar scoliosis (DLS) who had undergone long sacroiliac fusion surgery. METHODS: A multi-center retrospective study including 88 DLS patients underwent the surgical procedure of long sacroiliac fusion with instrumentations was performed. Comparisons of radiographic and quality-of-life (QoL) data among that at the pre-operation, the 3rd month and the final follow-up were performed. The correlations between the LL correction and the changes in other spinopelvic parameters were explored using Pearson-correlation linear analysis and linear regression analysis. The correlation coefficient (r) and the adjusted r2 were calculated subsequently. RESULTS: All radiographic and QoL data improved significantly (P < 0.001) after the surgical treatments. The LL correction correlated (P < 0.001) with the changes in the sacral slope (SS, r = 0.698), pelvic tilt (PT, r = -0.635), sagittal vertical axis (SVA, r = -0.591), T1 pelvic angle (TPA, r = -0.782), and the mismatch of pelvic incidence minus lumbar lordosis (PI-LL, r = -0.936), respectively. Moreover, LL increased by 1° for each of the following spinopelvic parameter changes (P < 0.001): 2.62° for SS (r2 = 0.488), -4.01° for PT (r2 = 0.404), -4.86° for TPA (r2 = 0.612), -2.08° for the PI-LL (r2 = 0.876) and -15.74 mm for SVA (r2 = 0.349). Changes in the thoracic kyphosis (r = 0.259) and pelvic femur angle (r = 0.12) were independent of the LL correction, respectively. CONCLUSIONS: LL correction correlated significantly to the changes in spinopelvic parameters; however, those independent variables including the thoracic spine and hip variables probably be remodeled themselves to maintain the full-body balance in DLS patients underwent the correction surgery.

Trichinella spiralis-Secreted Products Promote Collagen Capsule Formation through TGF-ß1/Smad3 Pathway.

Trichinella spiralis (T. spiralis) muscle larvae colonize in the host's skeletal muscle cells, which are surrounded by collagen capsules. The mechanism underlying muscle stage larva-induced collagen capsule formation remains unknown. To clarify the mechanism, a T. spiralis muscular-infected mouse model was established by a single lateral tail vein injection with 20,000 T. spiralis newborn larvae (NBL). The infected mice were treated with or without SB525334 (TGF-ß1 receptor type I inhibitor). Diaphragms were obtained post-infection, and the expression levels of the TGF-ß1/Smad3 pathway-related genes and collagen genes (type IV and VI) were observed during the process of collagen capsule formation. The changes in myoblasts under stimulation of the excretory-secretory (ES) products of NBL with or without SB525334 were further investigated. Results showed that the expression levels of type IV collagen gene, type VI collagen gene, Tgfb1, and Smad3 were significantly increased in infected mice muscle cells. The expression levels of all the above genes were enhanced by the products of NBL in myoblast cells. These changes were reversed by co-treatment with SB525334 in vivo and in vitro. In conclusion, the TGF-ß1/Smad3 pathway can be activated by T. spiralis infection in muscle cells. The activated TGF-ß1/Smad3 pathway can stimulate the secretion of collagens by myocytes and plays a promoting role in the process of collagen capsule formation. The research has the limitation that the protein identification of the products of NBL has yet to be performed. Therefore, the specific components in the T. spiralis ES products that induce collagen synthesis should be further investigated.

A novel microenvironment regulated system CAR-T (MRS.CAR-T) for immunotherapeutic treatment of esophageal squamous carcinoma.

Chimeric antigen receptor T cell immunotherapy has achieved promising therapeutic effects in the treatment of hematological malignancies. However, there are still many obstacles, including on-target off-tumor antigen expression, that prevent successful application to solid tumors. We designed a tumor microenvironment (TME) regulated system chimeric antigen receptor T (MRS.CAR-T) which can only be auto-activated in the solid TME. B7-H3 was selected as the target antigen for esophageal carcinoma. An element comprising a human serum albumin (HSA) binding peptide and a matrix metalloproteases (MMPs) cleavage site was inserted between the 5' terminal signal peptide and single chain fragment variable (scFv) of the CAR skeleton. Upon administration, HSA bound the binding peptide in MRS.B7-H3.CAR-T effectively and promoted proliferation and differentiation into memory cells. MRS.B7-H3.CAR-T was not cytotoxic in normal tissues expressing B7-H3 as the antigen recognition site in the scFv was cloaked by HSA. The anti-tumor function of MRS.B7-H3.CAR-T was recovered once the cleavage site was cleaved by MMPs in the TME. The anti-tumor efficacy associated with MRS.B7-H3.CAR-T cells was improved compared to classic B7-H3.CAR-T cells in vitro and less IFN-γ was released, suggesting a treatment that may induce less extent of cytokine release syndrome-mediated toxicity. In vivo, MRS.B7-H3.CAR-T cells had strong anti-tumor activity and were safe. MRS.CAR-T represents a novel strategy to improve the efficacy and safety of CAR-T therapy in solid tumors.

Association of spinopelvic index with proximal junctional failure developing in adult spinal deformity after surgical treatment: an observational study.

BACKGROUND: Those pelvic parameters of sacral slope (SS) and pelvic tilt (PT) correlated significantly to lumbar spine and hip joints respectively. We proposed the match between SS and PT, namely spinopelvic index (SPI), in order to investigate whether the SPI correlated to proximal junctional failure (PJF) in adult spinal deformity (ASD) after correction surgery. METHODS: Ninety-nine ASD patients who had undergone long-fusion (≥ 5 vertebras) surgeries were reviewed retrospectively in two medical institutions from January 2018 to December 2019. Those SPI were calculated with the equation: SPI = SS/PT, and analyzed using the receiver operating characteristic curve (ROC) analysis. All participants were subdivided into the observational and control group. Comparisons of demographics, surgical and radiographic data between the two groups were performed. A Kaplan-Meier curve and log-rank test was used to analyze the differences in PJF-free survival time, and the 95% confidence intervals (CI) were recorded respectively. RESULTS: Nineteen patients suffering from PJF had much smaller postoperative SPI (P = 0.015), but much larger TK postoperatively (P < 0.001). ROC analysis determined the best cutoff value of 0.82 for SPI (sensitivity = 88.5%, specificity = 57.9%; AUC = 0.719, 95%CI: 0.612-0.864; P = 0.003). There were 19 and 80 cases in the observational (SPI ≤ 0.82) and control group (SPI > 0.82) respectively. The incidence of PJF in the observational group was much higher (11/19 VS 8/80, P < 0.001); further logistic regression analysis showed that SPI ≤ 0.82 was associated with increased odds of PJF (odds ratio: 12.375; 95%CI: 3.851-39.771). PJF-free survival time in the observational group decreased significantly (P < 0.001, log-rank test), moreover, multivariate analysis demonstrated that a value of SPI ≤ 0.82 (HR 6.626, 95%CI: 1.981-12.165) was significantly associated with PJF. CONCLUSIONS: For ASD patients underwent long-fusion surgeries, the SPI should be over 0.82. The incidence of PJF may increase by 12-fold in such individuals with the immediate SPI ≤ 0.82 postoperatively.

G-Quadruplex DNAzyme-Substrated CRISPR/Cas12 Assay for Label-Free Detection of Single-Celled Parasitic Infection.

Early diagnosis of parasitic diseases can dramatically alleviate medical, economic, and social burdens. Herein, we report a sensitive and label-free assay for diagnosing single-celled parasitic infections using G-quadruplex (G4) DNAzyme as a reporter for CRISPR/Cas12. The substitution of a fluorescent DNA reporter with G4 DNAzyme increased the sensitivity for detecting Leishmania donovani (L. donovani) by 5 times and obviated the need for using chemically labeled DNA probes. The G4 DNAzyme-substrated CRISPR/Cas12 (GsubCas12) assay yielded a limit of detection of 3.1 parasites in the detection of cultured L. donovani and was further applied to analyze L. donovani in infected mice. The results showed that the GsubCas12 assay could positively detect L. donovani in spleen samples from infected mice about 2 weeks after low-dose inoculation, nearly 2 weeks earlier than that of parasitological analysis. GsubCas12 assay is promising as a diagnostic tool for parasitic infection in resource-limited regions.

Factors Related to Preoperative Coronal Malalignment in Degenerative Lumbar Scoliosis: An Analysis on Coronal Parameters.

OBJECTIVES: Recently the effects of coronal malalignment (CM) in degenerative lumbar scoliosis (DLS) have been reported, however, there was few studies on the correlated parameters of coronal alignments at pre-operation. The aims of this current study were to investigate the associations of coronal parameters with scoliosis and coronal alignment, and to explore the relationships between the coronal pelvic tilt and coronal alignment in DLS. METHODS: One hundred and sixty-one DLS patients in our hospital from May 2016 to December 2020 were reviewed and documented. The coronal balance distance (CBD, the offset between the center of C7 and the plumb line drawn from the center of S1), major Cobb (MC), fractional Cobb (FC), L4 coronal tilt, L5 coronal tilt, coronal pelvic tilt, apical rotation, and the vertebras in major curve were measured and documented. CM was considered if the CBD ≥ 30mm. All of those participants were assigned into group A (CBD ≥ 30 mm) and group B (CBD < 30 mm). Comparisons of demographic and radiographic data were performed between groups A and B. Pearson correlation and further multiple regression with stepwise method analysis were used to investigate those coronal parameters correlated to MC and CBD, respectively. RESULTS: Thirty-one patients suffering from CM were assigned into group A, and the rest of 130 patients were assigned to group B accordingly. Then the incidence of CM was about 19.3% (31/161). Patients in group A had less vertebras in the main curve (P = 0.009), however, the apical rotation (P < 0.001) and the L4 coronal tilt (P = 0.007) were much larger. Although the MC (P = 0.426) and FC (P = 0.06) had no difference between the two groups, the match between MC and FC was much smaller (p = 0.021) in group A. The coronal pelvic tilt correlated significantly with FC (r = 0.552, p < 0.001), but mildly with MC (r = -0.366, p < 0.001), L4 coronal tilt (r = 0.348, p < 0.001), and L5 coronal tilt (r = 0.351, p < 0.001), respectively. The CBD correlated strongly with L4 coronal tilt (r = -0.471, p < 0.001) and L5 coronal tilt (r = -0.468, p < 0.001), respectively, but mildly with FC (r = -0.255, p = 0.016). Further multiple regression analysis revealed that only L4 coronal tilt was the independent factor for MC (r2  = 0.549, p < 0.001) and CBD (r2  = 0.221, p < 0.001), respectively. CONCLUSIONS: The prevalence of CM in DLS patients is about 19% at pre-operation. With similar major Cobb, the less the vertebras in the major curve, the larger the CBD. L4 coronal tilt may correlate significantly to scoliosis and CBD. Coronal pelvic tilt may be just one of the compensations for the scoliosis deformity but effects CBD directly.

Intervertebral-spreader-assisted anterior cervical discectomy and fusion prevents postoperative axial pain by alleviating facet joint pressure.

OBJECTIVE: To evaluate the relationship of postoperative cervical axial pain with different vertebral distraction methods used during ACDF procedures in cervical spondylosis patients. METHODS: Ninety-four single-level cervical spondylotic myelopathy patients with significantly loss of intervertebral disc height who underwent ACDF surgery in our institute between January 2018 and January 2020 were enrolled. Cervical spine lateral radiographs were taken preoperatively, 3 days, 1-month, 2-month and 6-month after the surgery. The intervertebral disc height (IDH), interfacet distance (IFD), JOA (Japanese Orthopaedic Association) score, NDI (Neck Disability Index) score, nVAS (Neck Visual Analogue Scale) score and aVAS (Arm Visual Analogue Scale) score were measured. The correlation of clinical parameters and intervertebral disc height was evaluated. Then the correlation of clinical outcomes and different distraction method was evaluated. The patients were randomly divided into two groups, one uses Casper pin distractor system alone for distraction (Caspar alone group) and the other uses spreader assisted distraction method (Casper + spreader group). In biomechanical study, four cervical spine cadavers were selected for facet pressure measurements under different vertebral distraction methods, and the facet joint pressure was measured using force sensors. RESULTS: Satisfactory cervical fusion and neurological recovery were achieved in all patients. No significant correlation of IDH, IFD, JOA, NDI or aVAS with nVAS score was found. No significant difference between the change in disc height and clinical outcomes was found. However, by comparing the clinical parameters of patients in different vertebral distraction groups, we found significant changes in the early nVAS and NDI scores (P = 0.11, P = 0.48) of the Casper + spreader group (3 days postoperation), and was associated with a better nVAS score at 2 months postoperation (P < 0.05). The biomechanical study in cervical cadavers also showed significantly and continuously decreased facet joint pressure in the spreader assisted vertebral distraction group (P < 0.01). CONCLUSIONS: Spreader-assisted vertebral distraction method effectively alleviates postoperative neck pain in degenerative cervical spondylosis patients treated with ACDF. The mechanism may be related to the transient relief of facet joint pressure during the vertebral distraction procedure in ACDF.

Pedicle Subtraction Osteotomy in Lateral Position: A New Strategy for Correcting Severe Thoracolumbar Kyphosis Combined with Hip Flexion Contracture in Ankylosing Spondylitis.

OBJECTIVE: To describe spinal osteotomy in lateral position, which might be a new strategy for correcting thoracolumbar kyphotic deformity combined with severe hip flexion contracture, and to present two cases in which this method was successfully performed. METHODS: Spinal osteotomies in lateral position were performed in two patients with severe thoracolumbar kyphosis combined with hip flexion contracture, which was not suitable for operation in the prone position. Case 1: a 33-year-old female AS patient still had severe hip flexion contracture due to poor rehabilitation after total hip replacement (THR). The range of movement of the hip was only about 15° in right and 10° in left. Pre-operativethoracic kyphosis (TK), thoracolumbar kyphosis (TLK), lumbar lordosis (LL), and sagittal vertical axis (SVA) were 52.4°, 49.1°, 42.7°, and 315 mm, respectively. Pedicle subtraction osteotomy (PSO) at L3 was performed in the lateral position. The eggshell procedure was used during osteotomy. Case 2: a 45-year-old male AS patient presented coexisting rigid thoracolumbar kyphosis and hip flexion contracture. The range of movement of the hip was only about 20° in right and 25° in left. Pre-operativeTK, TLK, LL and SVA were 34.9°, 66.8°, 58.8° and 290.8 mm, respectively. PSO at L2 was performed in lateral position. The eggshell procedure was also used. RESULTS: Sagittal malalignments of both patients were greatly improved. For case 1, the total operation time was 5.5 h. The blood loss was 1500 mL and the amount of allogeneic blood transfusion was 1580 mL during the operation. SVA was reduced to 127 mm and LL decreased from preoperative 42.7° to -28.4°. The correction angle through L3 was 34.7° and the correction angle through the osteotomy segment was 62.9°. For case 2, the duration of surgery was 6.5 h. The operative blood loss was 2000 mL and the total amount of blood transfusion was 2020 mL. SVA was reduced to 209.8 mm and LL decreased from preoperative 58.8° to 9.2°.The correction angle through L2 was 37.1° and the correction angle through the osteotomy segment was 55°. No intra-operative or post-operative complications were observed. Six months after PSO, case 1 had good posture for standing and sitting. The case 2 underwent bilateral THRs nine months after PSO. CONCLUSION: PSO could be performed in the lateral position successfully. For AS patients who cannot be placed in the prone position due to coexisting severe thoracolumbar kyphosis and hip flexion contracture, performing spinal osteotomy in the lateral position as the first step is an alternative.

Correlation of Acetabular Anteversion and Thoracic Kyphosis Postoperatively with Proximal Junctional Failure in Adult Spinal Deformity Fused to Pelvis.

OBJECTIVES: To investigate whether the immediate thoracic kyphosis (TK) and acetabular anteversion (AA) postoperatively are correlated with proximal junctional failure (PJF) in adult spinal deformity (ASD) patients underwent surgical treatment. METHODS: This is a retrospective study. Following institutional ethics approval, a total of 57 patients (49 Female, eight Male) with ASD underwent surgery fused to sacroiliac bone (S1, S2, or ilium) from March 2014 to January 2019 were included. All of those patients were followed up for at least 2 years. Demographic, radiographic and surgical data were recorded. The maximum range of flexion motion (F-ROM) and extension motion (E-ROM) actively of hip joints was measured and recorded at pre- and postoperation. The sum of F-ROM and E-ROM was defined as the range of hip motion (H-ROM). Receiver operating characteristic (ROC) curve analysis was used to obtain the cut off value of parameters for PJF. A Kaplan-Meier curve and log-rank test were used to analyze the differences in PJF-free survival. RESULTS: In all, 14 patients developed PJF during follow-up. Comparisons between patients with and without PJF showed significant differences in immediate TK (P < 0.001) and AA (P = 0.027) postoperatively. ROC curve analysis determined an optimal threshold of 13° for immediate AA postoperatively (sensitivity = 74.3%, specificity = 85.7%, area under the ROC curve [AUC] = 0.806, 95% CI [0.686-0.926]). Nineteen patients with post-AA ≤13° were assigned into the observational group, and 38 patients with post-AA >13° were being as the control group. Patients in the observational group had smaller H-ROM (P = 0.016) and F-ROM (P < 0.001), but much larger E-ROM (P < 0.001). There were 10 patients showing PJF in the observational group and four in the control group (10/9 vs 4/34, P < 0.001). PJF-free survival time significantly decreased in the observational group (P = 0.001, log-rank test). Furthermore, patients in the observational group had much larger TK (post-TK, P = 0.015). The optimal threshold for post-TK (sensitivity = 85.7%, specificity = 76.7%; AUC = 0.823, 95% CI [0.672-0.974]) was 28.1° after the ROC curve was analyzed. In the observational group, those patients with post-TK ≥28.1° had significantly higher incidence of PJF (9/2 vs 1/7, P < 0.001) than those with post-TK < 28.1°. Moreover, PJF-free survival time in those patients significantly decreased (P = 0.001, log-rank test). CONCLUSIONS: ASD patients with acetabular anteversion of ≤13° at early postoperation may suffer significantly restricted hip motion and much higher incidence of PJF during follow-up, moreover, in those patients, postoperative TK ≥28.1° would be a significant risk factor for PJF developing.

Spine-Pelvis-Hip Alignments in Degenerative Spinal Deformity Patients and Associated Procedure of One-Stage Long-Fusion with Multiple-Level PLIF or Apical-Vertebra Three Column Osteotomy-a Clinical and Radiographic Analysis Study.

OBJECTIVE: To explore the spine-pelvis-hip alignments in degenerative spinal deformity (DSD) patients, and compare the outcomes in the procedure of long-fusion with posterior lumbar inter-body fusion (PLIF) or single-level three-column osteotomy (STO) at lower lumbar level (LLL, L3 -S1 ) and thoracolumbar levels (TLL, T10 -L2 ) for those patients. METHODS: This is a retrospective study. Following institutional ethics approval, a total of 83 patients (Female, 67; Male, 16) with DSD underwent long-fusion with PLIF or STO surgery between March 2015 and December 2017 were reviewed. All of those patients were assigned into LLL and TLL groups. The average age at surgery was 65.2 years (SD, 8.1). Demographic (age, gender, BMI, and comorbidities), radiographs (both coronal and sagittal parameters) and health-related quality of life (HRQOL) assessments were documented. The radiographic parameters and HRQOL-related measurements at pre- and post-operation were compared with paired-samples t test, and those variables in the two groups were analyzed using an independent-sample t test. The relationships between pelvic incidence (PI) and other sagittal parameters were investigated with Pearson correlation analysis. The Pearson χ2 or Fisher's exact was carried out for comparison of gender, incidence of comorbidities and post-operative complications. RESULTS: There were 53 and 30 patients in the LLL and TLL groups respectively. Those spino-pelvic radiographic parameters had significant improvements after surgeries (P < 0.001). The patients in the two group with different pre-operative thoracolumbar kyphosis (TLK, P = 0.003), PI (P = 0.02), and mismatch of PI minus lumbar lordosis (PI-LL, P = 0.01) had comparable post-operative radiographic parameters except PI (P = 0.04) and pelvic-femur angle (PFA, P = 0.02). Comparing the changes of those spine-pelvic-hip data during surgeries, the corrections of TLK in TLL group were significant larger (P = 0.004). Pearson correlation analysis showed that there were negative relationship between PI and TLK (r = -0.302, P = 0.005), positive relationship between PI and LL (r = 0.261, P = 0.016) at pre-operation. Those patients underwent the surgical procedure that long-segment instrumentation and fusion with STO would have higher incidence of complications involving longer operative timing (P = 0.018), more blood loss (P < 0.001), revision surgery (P = 0.008), and cerebrospinal fluid leakage (P = 0.001). All the HRQOL scores significantly improved at final follow-up (P < 0.001), with no difference of intra-group. CONCLUSION: Patients suffered de-novo scoliosis or hyper-kyphosis with low PI would be vulnerable to significant thoracolumbar degeneration, and have more changes of spine-pelvis-hip data after long-fusion surgery, however, those with high PI would be closed to significant lumbar degeneration. Although spine-pelvis-hip alignments in DSD patients can be restored effectively after long-fusion with PLIF or STO, the incidence of complications in patients underwent STO was significant higher than that in patients performed multi-level PLIF.

Association of Sagittal Spinopelvic Realignment with Correction in Lower Lumbar Lordosis after Surgical Treatment in Degenerative Lumbar Scoliosis.

OBJECTIVE: To assess the effect that correction of lower lumbar lordosis (3L) has on global spine realignment due to the key role of 3L for scoliosis surgery in patients with degenerative lumbar scoliosis (DLS). METHODS: This study is a retrospective review performed between June 2018 and January 2020, including consecutive patients with DLS. Only patients age ≥ 45 years who had already undergone a selective root block operation and had the procedure of long-fusion extending to pelvis and posterior lumbar interbody fusion (PLIF) at lower lumbar spine (L4 -S1 ) were retained for analysis. Spinopelvic parameters measured included thoracic kyphosis (TK), lumbar lordosis (LL), 3L, pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), T1 pelvic angle (TPA), and sagittal vertical axis (SVA) at pre-operation and the third month follow-up. The mismatch (PI-LL) was calculated subsequently. Pearson correlation and linear regression analysis were performed to explore the association of the changes in global spinopelvic parameters with 3L correction. RESULTS: Thirty-nine patients (five males, 34 females) with the average age of 63.84 years (SD 7.53; range, 45-75 years) at the time of surgery were identified. All patients had the surgical procedure of long-fusion (≥4 vertebras) with PLIF at lower lumbar spine between L4 and S1 spine. Lower instrumented vertebras (LIV) fused to pelvis (S1 , 14; S2 , 18; ilium, 7) were operated in all patients. Seventeen patients were with upper instrumented vertebras (UIV) at thoracolumbar spine (L2 -T11 ), and 22 patients at thoracic spine (T10 and above). The median of instrumented segments was 10 (5-14). 3L significantly increased (P = 0.02) after surgical treatment by mean change of 4.21° (range, -19.7° to +22.2°). Perioperatively, all spinopelvic parameters regarding to TK, LL, SS, PT, TPA, SVA, and mismatch (PI-LL) had significant changes (P < 0.001). The change in 3L correlated significantly with the changes in spinopelvic parameters (r = 0.772 for LL, -0.589 for SVA, -0.439 for TPA, and -0.428 for PI-LL). After linear regression analysis, the formulas were obtained: d-LL = 14.977 + 0.636 × d-3L, (R2 = 0.596); d-(PI-LL) = 16.575 + 0.62 × d-3L, (R2 = 0.183); d-TPA = -7.284 to 0.358 × d-3L, (R2 = 0.193); d-SVA = -30.556-2.639 × d-3L (R2 = 0.347). CONCLUSIONS: Correction in lower lumbar lordosis, following the surgical procedure of long-fusion with PLIF at lower lumbar spine, could result in significant changes in full-spine parameters. The significant association of changes in each of global spine parameter with the correction of 3L perioperatively could provide important information for surgeons to make a surgical plan for spinal correction.

Chaperone-mediated autophagy affects tumor cell proliferation and cisplatin resistance in esophageal squamous cell carcinoma.

BACKGROUND: Chaperone-mediated autophagy (CMA) is a lysosomal degradation pathway of selective soluble proteins. Lysosomal membrane associated protein 2a (LAMP2a) is the lysosomal membrane receptor of CMA and influences CMA activity. Although it has been suggested that higher expression of LAMP2a is associated with more advanced tumor node metastasis (TNM) stages and shorter survival time in patients with esophageal squamous cell carcinoma (ESCC), the underlying mechanism has not been known yet. METHODS: In this study, we modulated the activity of CMA through LAMP2a or small molecular compounds in human ESCC cells to investigate its role in ESCC. RESULTS: We found that down-regulating the activity of CMA could inhibit the proliferation and colony formation of ESCC cells as well as increase their sensitivity to cisplatin. CONCLUSIONS: Our results promote better understanding of how CMA affects human ESCC and provide a new therapeutic target against ESCC through down-regulating LAMP2a.

A Tumor-Targeted Replicating Oncolytic Adenovirus Ad-TD-nsIL12 as a Promising Therapeutic Agent for Human Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most lethal cancers in China and existing therapies have been unable to significantly improve prognosis. Oncolytic adenoviruses (OAds) are novel promising anti-tumor drugs and have been evaluated in several cancers including ESCC. However, the antitumour efficacy of the first generation OAds (H101) as single agent is limited. Therefore, more effective OAds are needed. Our previous studies demonstrated that the novel oncolytic adenovirus Ad-TD-nsIL12 (human adenovirus type 5 with E1ACR2, E1B19K, E3gp19K-triple deletions)harboring human non-secretory IL-12 had significant anti-tumor effect, with no toxicity, in a Syrian hamster pancreatic cancer model. In this study, we evaluated the anti-tumor effect of Ad-TD-nsIL12 in human ESCC. The cytotoxicity of Ad-TD-nsIL12, H101 and cisplatin were investigated in two newly established patient-derived tumor cells (PDCs) and a panel of ESCC cell lines in vitro. A novel adenovirus-permissive, immune-deficient Syrian hamster model of PDCs subcutaneous xenograft was established for in vivo analysis of efficacy. The results showed that Ad-TD-nsIL12 was more cytotixic to and replicated more effectively in human ESCC cell lines than H101. Compared with cisplatin and H101, Ad-TD-nsIL12 could significantly inhibit tumor growth and tumor angiogenesis as well as enhance survival rate of animals with no side effects. These findings suggest that Ad-TD-nsIL12 has superior anti-tumor potency against human ESCC with a good safety profile.

Polymorphisms of the kappa casein (CSN3) gene and inference of its variants in water buffalo (Bubalus bubalis).

Kappa casein plays a crucial role in the formation of stable casein micelles and has a key influence on milk-clotting properties. However, current understanding of buffalo CSN3 gene polymorphisms is not sufficient. In this study, the polymorphisms in the complete coding sequence (CDS) of the buffalo CSN3 were detected using PCR product direct sequencing. The CDS of CSN3 for river and swamp buffalo was the same in length, which contained an open reading frame of 573 nucleotides encoding a peptide containing 190 amino acid residues. A total of eight single nucleotide polymorphisms (SNPs) was identified in two types of buffalo. Among them, c.86C>T, c.252G>C, c.445G>A, c.467C>T and c.516A>C were non-synonymous, which leads to p.Pro8Leu, p.Lys63Asn, p.Val128Ile, p.Thr135Ile and p.Glu151Asp substitutions in buffalo kappa casein ( κ -CN), respectively. The substitution of p.Thr135Ile may exert a vital effect on the function of buffalo κ -CN. Eleven haplotypes were defined based on the SNPs found in buffalo, and accordingly, seven protein variants and four synonymous variants of buffalo κ -CN were inferred, called variants A, B, B 1 , C, C 1 , C 2 , D, E, F, F 1 and G. The variants observed in water buffalo did not exist in the Bos genus. In addition, 14 amino acid differential sites of κ -CN between buffalo and the Bos genus were identified, of which 3 were located at glycosylation sites (80S, 96T, 141S) and 4 at phosphorylation sites (19S, 80S, 96T, 141S). It is speculated that they may lead to differences in the physicochemical properties of κ -CN between buffalo and the Bos genus. This study will lay a foundation for exploring the association between the variation in the CSN3 gene and the lactation traits of buffalo.

Coronal Imbalance in Adult Spinal Deformity Following Posterior Spinal Fusion With Instrument: A Related Parameters Analysis.

STUDY DESIGN: A retrospective radiographic study. OBJECTIVE: To explore the radiological parameters which correlated to postoperative immediately coronal imbalance in adult spinal deformity (ASD) and to determine whether preoperative coronal imbalance affects postoperative coronal imbalance following posterior multi-level fusion with instruments and osteotomy operation. SUMMARY OF BACKGROUND DATA: There was paucity of literature paying attention to the postoperative immediately coronal imbalance after operation. METHODS: The study included 67 consecutive patients with ASD who underwent posterior multi-level fusion with instruments and osteotomy operation. The radiological parameters, measured on the pre- and postoperative anteroposterior and lateral radiographs, were compared and analyzed. Patients were divided into three groups (group A, B, and C) according to preoperative coronal balance distance (pre-CBD) and the relation of cervical 7 plumb line (C7PL), and the convex of curvature. To analyze the radiological parameters of the three groups. RESULT: Differences of the radiological parameters between pre- and postoperation concerning Cobb angles, degree of apical vertebra rotation, thoracic kyphosis (TK), thoracic lumber kyphosis (TLK), lumber lordosis (LL), sacral slope (SS), pelvic tilt (PT), and sagittal vertical axis (SVA), were significant (P < 0.05). Pelvic incidence (PI), pre-CBD, and postoperative coronal balance distance (post-CBD) had no change (P > 0.05). The ratio of coronal imbalance in pre- and postoperation was 31.34% (21/67) and 40.30% (27/67), respectively, which had significant difference (P = 0.02). Significant correlations were observed among post-CBD, pre-CBD (P < 0.001), and d-Cobb (pre-Cobb - post-Cobb) (P = 0.002), post-CBD = -2.737 - 0.924*d-Cobb + 0.356*pre-CBD. The ratio of postoperative immediately coronal imbalance of the group C was much higher than other two groups (P = 0.01). CONCLUSION: The sagittal alignments in ASD patients would be improved effectively after posterior multi-level fusion with instruments and osteotomy operation. There were significant correlations among post-CBD, pre-CBD, and d-Cobb. Patients in group C may be at greater risk for immediate postoperative coronal imbalance after operation. LEVEL OF EVIDENCE: 3.

Optimal Pelvic Incidence Minus Lumbar Lordosis Mismatch after Long Posterior Instrumentation and Fusion for Adult Degenerative Scoliosis.

OBJECTIVE: To evaluate the influence of Scoliosis Research Society (SRS)-Schwab sagittal modifiers of pelvic incidence minus lumbar lordosis mismatch (PI-LL) on clinical outcomes for adult degenerative scoliosis (ADS) after long posterior instrumentation and fusion. METHODS: This was a single-institute, retrospective study. From 2012 to 2014, 44 patients with ADS who underwent posterior instrumentation and fusion treatment were reviewed. Radiological evaluations were investigated by standing whole spine (posteroanterior and lateral views) X-ray and all radiological measurements, including Cobb's angle, LL, PI, and the grading of vertebral rotation, were performed by two experienced surgeons who were blind to the operations. The patients were divided into three groups based on postoperative PI-LL and the classification of the SRS-Schwab: 0 grade PI-LL (<10°, n = 13); + grade PI-LL (10°-20°, n = 19); and ++ grade PI-LL (>20°, n = 12). The clinical outcomes were assessed according to Japanese Orthopaedic Association (JOA) score, Oswestry Disability Index (ODI), Visual Analog Scale (VAS), Lumbar Stiffness Disability Index (LSDI), and complications. Other characteristic data of patients were also collected, including intraoperative blood loss, operative time, length of hospital stay, complications, number of fusion levels, and number of decompressions. RESULTS: The mean operative time, blood loss, and hospital stay were 284.5 ± 30.2 min, 1040.5 ± 1207.6 mL, and 14.5 ± 1.9 day. At the last follow-up (2.6 ± 0.6 years), the radiological and functional parameters, except the grading of vertebral rotation, were all significantly improved in comparison with preoperative results (P < 0.05), but it was obvious that an ideal PI-LL (≤10°) was not achieved in some patients. Significant differences were only observed among the three groups in the ODI and LSDI. Patients with + grade PI-LL seemed to have the best surgical outcome compared to those with 0 and ++ grade PI-LL, with the lowest ODI score (+ grade vs 0 grade, 17.3 ± 4.9 vs 26.0 ± 5.4; + grade vs ++ grade, 17.3 ± 4.9 vs 32.4 ± 7.3; P < 0.05) and lower LSDI (+ grade vs 0 grade, 1.6 ± 1.0 vs 3.5 ± 0.5, P < 0.05; + grade vs ++ grade, 1.6 ± 1.0 vs 0.6 ± 0.5, P > 0.05). A Pearson correlation analysis further demonstrated that LSDI was negatively associated with PI-LL. Furthermore, the incidence rate of postoperative complications was lower in patients with + grade PI-LL (1/19, 5.26%) than that in patients with 0 (2/13, 15.4%) and ++ grade PI-LL (3/12, 25%). CONCLUSION: Our present study suggest that the ideal PI-LL may be between 10° and 20° in ADS patients after long posterior instrumentation and fusion.