[Clinical study of the Cobb+1 to Cobb fusion strategy for Lenke 5C adolescent idiopathic scoliosis patients with the lower lumbar apex].

Objective: To investigate the indications and surgical outcome of Cobb+1 to Cobb fusion strategy in Lenke 5C adolescent idiopathic scoliosis (AIS) patients with the lower lumbar apex. Methods: The clinical data of Lenke 5C AIS patients treated in Nanjing Drum Tower Hospital from August 2015 to December 2018 were retrospectively analyzed. The patients were followed-up for at least 2 years after surgery and treated with selective Cobb+1 to Cobb fusion strategy. The patients were divided into the normal lumbar apex group (apex location of the main curve was between T12 and L1) and the lower lumbar apex group (apex location of the main curve was below the disc of L1/L2). The occurrence of proximal decompensation in the two groups was compared. In addition, according to whether the patients had proximal decompensation at the last follow-up, the patients in the lower lumbar apex group were further divided into proximal decompensation group and non-decompensation group. The radiographic parameters and Scoliosis Research Society-22 (SRS-22) scores of the two groups were compared. Results: A total of 52 patients (19 cases in the normal lumbar apex group and 33 cases in the lower lumbar apex group), aged (15.3±1.6) years, were followed up for 2-5 (3.2±1.2) years. Six patients (6/19) in the normal lumbar apex group and 5 cases (15.2%) in the lower lumbar apex group showed proximal decompensation during follow-up, and the incidence was significantly higher in the normal lumbar apex group (P=0.034). Within the lower lumbar apex group, the patients with proximal decompensation (n=5) showed similar Risser grade, baseline thoracic Cobb angle, and main Cobb angle as those without proximal decompensation(n=28), and the differences were all not statistically significant (all P>0.05). However, the baseline thoracic/lumbar apical vertebra translation (AVT) ratio was significantly larger in patients with proximal decompensation (0.6±0.2 vs 0.4±0.2, P=0.042), but the postoperative upper instrumented vertebra (UIV) tilt angle was similar (4.5°±2.3° vs 6.2°±3.4°, P=0.312). Conclusion: Cobb+1 to Cobb fusion strategy, selecting UIV at 1 level above upper end vertebra (UEV), could be performed in Lenke 5C patients with the lower lumbar apex location. In addition, UIV could be selected at UEV+1 in patients with small baseline thoracic curve.

Pharmacokinetics and safety of Padsevonil in healthy Chinese subjects and comparison of two sampling methods for Padsevonil quantification.

OBJECTIVE: Padsevonil (PSL) is a novel antiepileptic drug candidate that inhibits seizure activity in both presynaptic and postsynaptic ways. The pharmacokinetic (PK) profiles and volumetric absorptive microsampling (VAMS) application of PSL in the Chinese population are limited. The objectives of this study were to evaluate the PK profile of PSL and its 2 metabolites, the safety of PSL, and compare the PK profile of PSL from samples collected using the VAMS technique with that of conventional venous samples in healthy Chinese subjects. SUBJECTS AND METHODS: In this randomized, double-blind, placebo-controlled single-dose study, the participants received either 200 mg PSL or placebo. Blood samples for the PK variables were collected using both the traditional venous method and the VAMS Mitra® technique at the scheduled time points. The PK parameters of PSL and 2 metabolites were calculated, and the concentration agreement of VAMS and venous samples were also evaluated. RESULTS: A total of 14 subjects were enrolled. The concentration-time profile of PSL showed rapid absorption with a median tmax of 1.25 h (range: 0.5 to 3.0), followed by an apparent biphasic disposition. For PSL, the geometric means of AUC(0-t), AUC, Cmax, and t1/2 were 6,573 h*ng/mL, 6,588 h*ng/mL, 1,387 ng/mL, and 5.275 h, respectively. The geometric mean body weight-normalized AUC(0-t), AUC, and Cmax were 5,712 h*ng/mL, 5,725 h*ng/mL, and 1,205 ng/mL, respectively. The AUC(0-t), AUC, Cmax of PSL and metabolites in VAMS-dried blood were all lower than those in plasma. The Passing-Bablok regression showed that the PSL and metabolite concentrations obtained by VAMS analysis were comparable to those obtained by plasma at some time points. The most frequently reported treatment-emergent adverse events (TEAEs) were somnolence and dizziness. There were no serious TEAEs, severe TEAEs, discontinuations due to TEAEs, or deaths reported during this study. No clinically significant laboratory, vital signs, electrocardiograph (ECG), or physical examination results were reported. CONCLUSIONS: PSL has a favorable PK profile after single-dose oral administration and good safety properties in healthy Chinese volunteers. The regression analysis results of VAMS and plasma indicated that the application of VAMS for therapeutic drug monitoring in novel antiepileptic drug development is promising and needs further validation.

Nuclear translocation of YAP drives BMI-associated hepatocarcinogenesis in hepatitis B virus infection.

BACKGROUND AND AIMS: Hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC) development and progression. The aim of this study was to mechanistically investigate the involvement of Hippo signalling in HBV surface antigen (HBsAg)-dependent neoplastic transformation. METHODS: Liver tissue and hepatocytes from HBsAg-transgenic mice were examined for the Hippo cascade and proliferative events. Functional experiments in mouse hepatoma cells included knockdown, overexpression, luciferase reporter assays and chromatin immunoprecipitation. Results were validated in HBV-related HCC biopsies. RESULTS: Hepatic expression signatures in HBsAg-transgenic mice correlated with YAP responses, cell cycle control, DNA damage and spindle events. Polyploidy and aneuploidy occurred in HBsAg-transgenic hepatocytes. Suppression and inactivation of MST1/2 led to the loss of YAP phosphorylation and the induction of BMI1 expression in vivo and in vitro. Increased BMI1 directly mediated cell proliferation associated with decreased level of p16INK4a , p19ARF , p53 and Caspase 3 as well as increased Cyclin D1 and γ-H2AX expression. Chromatin immunoprecipitation and the analysis of mutated binding sites in dual-luciferase reporter assays confirmed that the YAP/TEAD4 transcription factor complex bound and activated the Bmi1 promoter. In chronic hepatitis B patients, paired liver biopsies of non-tumour and tumour tissue indicated a correlation between YAP expression and the abundance of BMI1. In a proof-of-concept, treatment of HBsAg-transgenic mice with YAP inhibitor verteporfin directly suppressed the BMI1-related cell cycle. CONCLUSION: HBV-associated proliferative HCC might be related to the HBsAg-YAP-BMI1 axis and offer a potential target for the development of new therapeutic approaches.

Wideband Direct Detection Constraints on Hidden Photon Dark Matter with the QUALIPHIDE Experiment.

We report direction detection constraints on the presence of hidden photon dark matter with masses between 20-30 µeV c^{-2}, using a cryogenic emitter-receiver-amplifier spectroscopy setup designed as the first iteration of QUALIPHIDE (quantum limited photons in the dark experiment). A metallic dish sources conversion photons, from hidden photon kinetic mixing, onto a horn antenna which is coupled to a C band kinetic inductance traveling wave parametric amplifier, providing for near quantum-limited noise performance. We demonstrate a first probing of the kinetic mixing parameter χ to the 10^{-12} level for the majority of hidden photon masses in this region. These results not only represent stringent constraints on new dark matter parameter space, but are also the first demonstrated use of wideband quantum-limited amplification for astroparticle applications.

Development of Superconducting On-chip Fourier Transform Spectrometers.

Superconducting On-chip Fourier Transform Spectrometers (SOFTS) are broadband, ultra-compact and electronic interferometers. SOFTS will enable kilo-pixel spectro-imaging focal planes, enhancing sub-millimeter astrophysics and cosmology. Particular applications include cluster astrophysics, cosmic microwave background (CMB) science, and line intensity mapping. This article details the development, design and bench-marking of radio frequency (RF) on-chip architecture of SOFTS for Ka and W-bands.

[Impact of C2-femoral heads center and sacroiliac fixation on the occurrence of post-operative proximal junctional kyphosis in adults with spinal deformity].

Objective: To analyze the relationship between post-operative proximal junctional kyphosis (PJK) and C2-femoral heads center (C2-FH), pelvic fixation in adult spinal deformity (ASD) patients, so as to provide a reference for the preoperative decision-making and the postoperative intervention timely. Methods: It was a retrospective study that analyzed 34 cases of ASD patients who underwent posterior pedicle screw fixation in Nanjing Drum Tower Hospital between January 2017 and May 2017. ASD patients were divided into two groups according to fixation options: the sacroiliac fixation group and the non-sacroiliac fixation group. The spine-pelvis parameters were evaluated on full-length X ray films of spine at preoperatively, 2 weeks postoperatively and the last follow-up, and the incidence of PJK was recorded. Results: A total of 34 ASD patients (3 males and 31 females) were included in this study, with an average age of (58±6) years. The mean follow-up period was (2.9±1.0) years (2.0-4.0 years). The age, follow-up time and various spine-pelvis parameters showed no significant differences between the two groups (all P>0.05). The immediate postoperative C2-FH in the sacroiliac fixation group was significantly lower than that in the non-sacroiliac fixation group [(-69.46±30.85) mm vs (-31.62±15.31) mm, P<0.001]. The incidence of PJK was as high as 50.0% (8/16) in patients with sacroiliac fixation, but it was only 22% (4/18) in patients without sacroiliac fixation (P=0.016). At the last follow-up, the C2-FH of both groups were both higher than -20 mm (both were approximately -15 mm, P=0.976), indicating that the C2-FH was compensated in both groups. Due to the loss of the distal compensation ability, the incidence of PJK in the sacroiliac fixation group was higher than that in the non-sacroiliac fixation group. Due to the fixation of pelvis and most of lumbar spine, no significant differences were found in lumbar lordosis (LL), pelvic tilt (PT) and sacral slope (SS) at the last follow-up in both groups when compared with those after the operation (all P>0.05); while the thoracic kyphosis (TK) and cervical lordosis (CL) increased significantly (both P<0.05) to compensate C2-FH at the last follow-up. Conclusion: It's demonstrated that C2-FH< -2 cm and pelvic fixation are high risk factors of PJK in ASD patients. It is suggested that both global sagittal balance and pelvic fixation should be considered in decision-making and corrective surgery, rather than only focusing on spine-pelvic parameters.

[Clinical study of selection of the upper instrumented vertebra at one level caudal to upper end vertebra in patients with Lenke 5C adolescent idiopathic scoliosis].

Objective: To investigate whether the upper instrumented vertebra (UIV) can be selected at one level caudal to upper end vertebra (UEV) in Lenke type 5C adolescent idiopathic scoliosis (AIS) patients. Methods: Total of 28 Lenke 5C AIS patients who underwent selective posterior fusion in Drum Tower Hospital of Nanjing University Medical School from September 2013 to September 2015 were included. There were 4 males and 24 females, with an age of (15.0±2.0) years, the Risser sign was graded 2-5. The following imaging parameters were measured on standing full spine X-ray before, immediately after the surgery and at the last follow-up: thoracolumbar/lumbar (TL/L) Cobb angle, coronal balance, UIV translation, lower instrumented vertebra (LIV) translation, UIV tilt, LIV tilt, and thoracic apical vertebral translation (T-AVT), lumbar apical vertebral translation (L-AVT). The patients were divided into two groups: decompensation group (n=6) and non-decompensation group (n=22). Radiographic parameters and Scoliosis Research Society (SRS)-22 scores were compared between the two groups. Results: Six cases (21.4%) had proximal decompensation at the last follow-up. There were no significant differences in Risser grade(3.8±1.0 vs 3.6±1.6), baseline thoracic Cobb angle(25.8°±2.2° vs 26.3°±6.4°) and TL/L Cobb angle(43.7°±3.4° vs 45.2°±6.5°) between the two groups (all P>0.05). However, the baseline lumbar/thoracic apical vertebra translation (L-T AVT ratio) was significantly higher in patients with proximal decompensation (6.3±1.3 vs 4.0±2.0, P=0.048). Conclusion: Selecting UIV at one level caudal to UEV, would not increase the incidence of proximal decompensation in Lenke 5C AIS patients with Risser higher than grade 2, the smaller baseline L-T AVT ratio, and with thoracic compensatory curve over 15°, and can obtain satisfactory clinical results.

[Occurrence of rod fracture and salvage methods after primary surgery of the congenital lumbosacral deformity associated with sacral agenesis].

Objective: To analyze the occurrence of rod fracture after surgery for lumbosacral deformity associated sacral agenesis and discuss the relevant salvage methods. Methods: The clinical records of 19 patients who underwent surgical treatment for lumbosacral deformity associated sacral agenesis from January 2001 to January 2018 were retrospectively reviewed, including 11 boys and 8 girls. The average age was (9.6±5.2) years. The outcomes of surgical correction and internal fixation were evaluated by postoperative regular follow-up. We also recorded the time and position of rod fracture occurrence. The Cobb angle, coronal balance and sagittal balance were measured and compared to analyze the corresponding salvage methods and revision outcomes. Results: Three patients encountered rod fracture during follow-up, so the incidence of rod fracture after surgery for lumbosacral deformity associated sacral agenesis was 15.8%(3/19). Based on their own conditions, we formulated the individualized strategy and performed the revision surgery through the posterior-only approach. The most critical step was abundant bone-grafting and fusion in the defected sacroiliac joint. After revision, the scoliotic Cobb angle improved in two patients (91.5° vs 47.5°, 49.0° vs 28.0°) and coronal balance improved in one patient (40.3 mm vs 24.3 mm). No complication reoccurred during follow-up. Conclusion: The rod fracture after surgery for lumbosacral deformity associated sacral agenesis is quite common, which is probably correlated with its unique deformed structure and biomechanical characteristics. The individualized salvage methods and adequate bone-grafting and fusion for the defected sacroiliac joint will guarantee the reconstruction and maintenance of spine balance after revision.

[Re-discussion on the diagnosis and treatment of cytomegalovirus hepatitis in children].

Cytomegalovirus hepatitis, especially infants with cholestatic liver disease or abnormal liver function, is of great concern to pediatricians. Previously, cytomegalovirus infection was the recognized cause of the disease. Therefore, a comprehensive scientific understanding of cytomegalovirus hepatitis requires an understanding of the basic knowledge of cytomegalovirus infection. Concurrently, it is necessary to standardize the indications of antiviral treatment in combination with the child's age, immune status and other potential diseases to avoid the abuse of antiviral drugs.

[Investigation on endometrium from menstrual blood as a source of non-invasive tissue].

Objective: To investigate the feasibility of a non-invasive sampling method by collecting menstrual blood and obtaining endometrium for further research in menstruation-related diseases. Methods: On the second day of menstruation, menstrual blood was collected with menstrual cups for 4 hours, and the menstrual endometrium was filtered through a metal screen for weighing, cryopreserved, immunohistochemical staining and cell culture. Results: The collection process was painless and non-invasive. In the control group, the menstrual volume was (9.1±0.7) ml, and the endometrial tissue weight was (91.0±14.7) g. In the endometriosis group, the menstrual volume was (9.6±1.9) ml (P=0.022), and the endometrial tissue weight was (134.7±43.9) g (P=0.057). Endometrial cell culture was successful in all patients and should not be contaminated. The growth curve was a finite cell line type. The expression of cytokeratin 19 and vimentin in menstrual endometrium and cells were positive. Conclusions: By collecting menstrual blood and filtering endometrial tissue, it is an ideal non-invasive sampling method. In combination with advanced experimental technology, menstrual endometrium make further researches of endometriosis, endometrial lesions or other menstruation-related diseases possible.