[Study on the mechanism of cross-linked hyaluronic acid-dexamethasone hydrogelin post-traumatic osteoarthritis].

Objective: To explore the mechanism of cross-linked hyaluronic acid-dexamethasone hydrogel (cHA-Dex) in inhibiting chondrocyte apoptosis and alleviating early post-traumatic osteoarthritis (PTOA). Methods: To generate PTOA model, anterior cruciate ligament transection (ACLT)was performed on SD rats (n=70), and the sham surgery group (n=70) was set as control. The changes in inflammatory indicators such as interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), matrix metalloproteinase-3 (MMP-3), and matrix metalloproteinase-13 (MMP-13) in the joint lavage fluid were measured at different time points (1-14 days, 5 rats at each time point) after surgery. The cHA-Dex (0.5 mg/ml) hydrogel (experimental group, n=70) and ordinary low-molecular-weight hyaluronic acid (HA) hydrogel premixed with Dex, that was, HA-Dex (0.5 mg/ml) hydrogel (control group, n=70) were injected into the joint cavity of PTOA rats, and the release amount and cumulative release amount of Dex in the joint fluid of rats at each time point(1-14 days, 5 rats at each time point) were detected to reveal the release mechanism of cHA-Dex hydrogel. The cartilage of knee joint of patients with osteoarthritis (OA) who underwent knee arthroplasty in the Second Hospital of Shanxi Medical University from January 2020 to December 2022 was taken for in vitro tissue block culture (Outbridge score=1 or 2,n=18). After the cartilage tissue block was treated with cHA-Dex hydrogel premixed with 0.1, 0.2, and 0.5 mg/ml Dex, the mRNA expression levels of IL-1ß, IL-6, TNF-α, MMP-3, and MMP-13 in the articular cartilage tissue block were detected. OA chondrocytes were isolated from cartilage samples using enzymatic hydrolysis and cultured in vitro (n=18). Chondrocytes were divided into 4 groups: saline, cHA hydrogel, Dex (0.5 mg/ml), and cHA-Dex (0.5 mg/ml) hydrogel group. The effects of different interventions on chondrocyte proliferation and apoptosis were tested. Results: The Osteoarthritis Research Society International (OARSI) score of safranine O-solid green staining in PTOA group was 3.34±0.35, and it was 1.17±0.21 in Sham group(P=0.010). The Meachim score of knee joint osteophytes in PTOA rats was significantly higher than that in the Sham group (2.66±0.41 vs 0.22±0.17, P=0.010), indicating PTOA model in rat was established successfully. The cHA-Dex hydrogel, which corresponded to the peak changes of inflammatory factors in the joints of PTOA rats in the early stage, was also released in the early stage and sustained-released in the late stage. After the OA articular cartilage tissue block was treated with cHA-Dex hydrogel premixed with 0.1, 0.2, and 0.5 mg/ml Dex, the mRNA expression levels of IL-1 ß, IL-6, TNF-α, MMP-3, and MMP-13 in the tissue block were reduced significantly (all P<0.05) and in a dose-dependent manner. Compared with Dex (0.5 mg/ml) alone group, the apoptosis rate of cHA-Dex (0.5 mg/ml) hydrogel group was significantly reduced (0.60±0.07 vs 6.63±0.98, P=0.010).Compared with the normal saline or the cHA hydrogel alone group, the cHA-Dex (0.5 mg/ml) hydrogel group had significant cell proliferation, and the difference at each time point were all significant statistically (all P<0.05). Conclusion: For the early inflammation of PTOA, cHA-Dex hydrogel can not only inhibit cartilage inflammation, but also reverse the increased apoptosis and decreased proliferation rate of chondrocytes caused by Dex, and finally alleviate the progress of PTOA by releasing Dex.

Effects of ciprofol for the induction of general anesthesia in patients scheduled for elective surgery compared to propofol: a phase 3, multicenter, randomized, double-blind, comparative study.

OBJECTIVE: Ciprofol is a newly developed intravenous sedative-hypnotic drug. The objective of the study was to prove whether ciprofol was non-inferior to propofol for the successful induction of general anesthesia. The ideal post-induction sedation level was assessed by comparing patients' clinical symptoms and their hemodynamic effects in responding to noxious stimuli, mostly tracheal intubation and bispectral index (BIS) alterations following ciprofol/propofol administration. PATIENTS AND METHODS: In this multi-center, randomized, double-blind phase 3 trial, selective surgery patients were randomly assigned in a 1:1 ratio to either ciprofol 0.4 mg/kg (n = 88) or propofol 2.0 mg/kg (n = 88) groups. The primary endpoint was the percentage of patients with successful anesthesia inductions. Secondary endpoints included the times to successful induction of general anesthesia and loss of the eyelash reflex, changes in BIS, as well as safety indicators. RESULTS: The anesthesia induction success rates for both ciprofol 0.4 mg/kg and propofol 2 mg/kg groups were 100.0%, with a 95% CI lower success limit of -4.18% difference between the two groups, indicating that ciprofol was non-inferior to propofol. For secondary outcomes, the average time to successful anesthesia and loss of the eyelash reflex were 0.91 min and 0.80 min for ciprofol and 0.80 min and 0.71 min for propofol, respectively. The pattern of BIS changes with ciprofol was similar to propofol and stable during the anesthesia maintenance period. Safety was comparable with 88.6% TEAEs in the ciprofol group compared to 95.5% in the propofol group. The incidence of injection pain was significantly lower in the ciprofol group compared to the propofol group (6.8% vs. 20.5%, p < 0.05). In addition, the patients treated with ciprofol had a lesser increase in blood pressure and heart rate, and fewer cases with BIS > 60 within 15 min of intravenous administration, which indicated that ciprofol may provide a better ideal sedation level during the post-induction period under an equivalent dosing regimen to propofol. CONCLUSIONS: Ciprofol for patients undergoing selective surgery is a new option for the induction of general anesthesia.

Efficacy and safety of HSK3486 for the induction and maintenance of general anesthesia in elective surgical patients: a multicenter, randomized, open-label, propofol-controlled phase 2 clinical trial.

OBJECTIVE: To evaluate the efficacy and safety of HSK3486 for the induction and maintenance of general anesthesia in elective surgical patients, but excluding emergency, cardiothoracic, cerebral and endoscopic sinus cases. PATIENTS AND METHODS: A total of 40 eligible patients were randomly assigned to HSK3486 (n = 30) or propofol (n = 10) dosage groups in a ratio of 3:1. Drugs were administered as a bolus injection of 0.4 mg/kg (HSK3486) or 2.0 mg/kg (propofol) for induction, followed by maintenance infusion with the same anesthetic. An additional 6 non-randomized patients received propofol (2.0 mg/kg) for induction and were given HSK3486 for maintenance. RESULTS: The primary efficacy endpoint - the success rate of anesthesia maintenance - was 100% in the 3 arms. The secondary efficacy endpoints included times from discontinuation of HSK3486 or propofol maintenance to full alertness, respiratory recovery, extubation and reaching the goal of the Aldrete score. Also, the proportion of patients who constantly maintained BIS40-60 or those with a period of BIS40-60 during maintenance anesthesia showed no significant difference in the HSK3486 and propofol groups (all p > 0.05). Patients who received HSK3486 exhibited a higher satisfaction score from anesthesiologists during the induction period (p = 0.024). The occurrence and types of treatment-emergent adverse events were similar among the 3 arms, both with a severity of grade 1 or 2. Drug-related hypotension occurred in 14 (46.7%) and 7 (70.0%) patients treated with HSK3486 and propofol, respectively. CONCLUSIONS: HSK3486 exhibited good efficacy for the induction and maintenance of general anesthesia and was well tolerated by patients who underwent elective surgery.

Idiopathic Neonatal Subpial Hemorrhage with Underlying Cerebral Infarct: Imaging Features and Clinical Outcome.

BACKGROUND AND PURPOSE: Neonatal subpial hemorrhage with underlying cerebral infarct is a previously described but poorly understood clinicoradiographic syndrome. We sought to further characterize the cranial ultrasound and MR imaging characteristics and associated outcomes of this condition across the full range of gestational ages, including extreme and very preterm neonates. MATERIALS AND METHODS: This was a single tertiary pediatric center retrospective case series. Brain MR imaging and cranial ultrasound of neonates with subpial hemorrhage with underlying cerebral infarct were identified from a population-based radiology registry (2006-2020). Original images were reviewed by 2 neuroradiologists blinded to history and outcome. Clinical presentation, course, and outcome at >12 months were abstracted from medical records. The diagnostic utility of cranial ultrasound was compared with that of MR imaging. RESULTS: Sixteen patients were included (median gestational age, 36.5 weeks; range, 27-41 weeks; 31% premature). MR images were obtained acutely at the time of presentation between days 0 and 9 of life. On T2WI and DWI, a consistent presence of a hypointense subpial bleed and an underlying hyperintense cerebral cortex were recognized, which created a distinct MR imaging pattern resembling the yin-yang symbol. Findings of all the MRAs and MRVs were normal. Cranial ultrasound detected 6 of 7 MR imaging lesions with sonographic features correlating well with MR imaging. The 3 extreme or very preterm neonates did not survive. The remainder survived with relatively mild neurologic deficits. CONCLUSIONS: Subpial hemorrhage with underlying infarction is a recognizable condition with unique MR imaging and sonographic features. Improved recognition may advance understanding of risk factors and outcomes.

MRI Head Coil Malfunction Producing Artifacts Mimicking Malformation of Cortical Development in Pediatric Epilepsy Work-Up.

We recently observed a type of MR imaging artifact that consistently mimics an abnormal appearance of the cerebral cortex, leading to initial misinterpretation and repeat scans. The artifact is caused by malfunction of part of the multichannel phased array head coil and is manifested by irregularity of cortical surface and gray-white matter junctions. The presence of such an artifact can be confirmed by assessing the background noise of the MR images and checking the coil element status on the MR imaging operator console.

Comparison of primary arthrodesis versus open reduction with internal fixation for Lisfranc injuries: Systematic review and meta-analysis.

Objective: Multiple studies have compared primary arthrodesis versus open reduction with internal fixation (ORIF) for surgical treatment of fractures of the Lisfranc joint, but their results have been inconsistent. Therefore, the present systematic review and meta-analysis was performed to compare the clinical efficacy of arthrodesis versus ORIF for the treatment of Lisfranc injuries. Methods: Through searching the Embase, PubMed, PMC, CINAHL, PQDT, and Cochrane Library databases (from July 1998 to July 2018), we identified five case-controlled trials and two randomized controlled trials that compared the clinical efficacy of primary arthrodesis and ORIF for treating Lisfranc injuries. The extracted data were analyzed using Review manager 5.3 software. Results: Through comparisons of data for primary arthrodesis and ORIF groups, we found no significant differences in the anatomic reduction rate, revision surgery rate, and total rate of complications between the different treatment approaches. However, arthrodesis was associated with a significantly better American Orthopedic Foot and Ankle Society (AOFAS) score, return to duty rate, and visual analog scale score with a lower incidence of hardware removal compared with ORIF. Conclusions: For the treatment for Lisfranc injuries, primary arthrodesis was superior to ORIF based on a higher AOFAS score, better return to duty rate, lower postoperative pain, and lower requirement for internal fixation removal. Further evidence from future randomized controlled trials with higher quality and larger sample sizes is needed to confirm these findings.

Bench test of phase measurement on dispersion interferometer for EAST.

In recent years, different traditional interferometers have been the necessary diagnostic of electronic density measurement on fusion devices. Until now, two main problems always influence the density measurement: the mechanical vibration and fringe jump in the calculation. The dispersion interferometer (DI) with a long-wavelength infrared wavelength is a good choice because mechanical vibrations can be canceled and the fringe jump can be inhibited. This paper describes the bench test of phase measurement using a wedge instead of plasma on the DI. The results show good agreement with the theoretical calculations. In the background measurement, this DI without a vibration isolation system has good performance, and the drift of the baseline is less than 2 × 1017 m-2 in 3 s and less than 5 × 1017 m-2 in 400 s. Plasma data will be obtained during the next campaign on EAST (Experimental and Advanced Superconducting Tokamak).

Deep ultraviolet light-emitting diodes with improved performance via nanoporous AlGaN template.

We report the performance enhancement of AlGaN-based deep ultraviolet light-emitting diodes (DUV LEDs) using AlGaN nanoporous template (NPT). The NPT was fabricated by the electrochemical etching method and served as the dislocation filtering layer and strain relieving layer. The n-AlGaN laterally regrown on NPT showed reduced dislocation density and mitigated compressive strain comparing with that on the as-grown template (AGT). A 23% improvement of internal quantum efficiency was achieved for the multiple quantum wells thereon. Moreover, the nanopores in the NPT transformed into elongated air voids during high temperature growth process, which could facilitate the escaping of photons by scattering and thus improve the light extraction efficiency. As a consequence, the DUV LED based on NPT demonstrated an increase of the light outpower by 50% at 20 mA than that on AGT.

Comparative study on the photoluminescence properties of monoclinic and cubic erbium oxide.

As a heavy rare earth oxide, erbium oxide (Er2O3) has many attractive properties. Monoclinic Er2O3 has useful properties not found in stable cubic Er2O3, such as unique optical properties and high radiation damage tolerance. In this study, pure cubic and mixed phase of cubic and monoclinic Er2O3 coatings were prepared. Photoluminescence properties of these coatings were characterized by a confocal micro-Raman spectrometer equipped with 325, 473, 514, 532, 633 nm lasers, and the influence of microstructure on the fluorescence properties was analyzed in detail. The room temperature fluorescence peaks of cubic Er2O3 were assigned. Furthermore, a novel method for rapid phase identification of Er3+ doped cubic and monoclinic rare earth sesquioxides at room temperature was proposed.

Association of TLR2 and TLR4 non-missense single nucleotide polymorphisms with type 2 diabetes risk in a southern Chinese population: a case-control study.

Toll-like receptors (TLRs), the triggers of the innate and adaptive immune responses, are involved in the pathogenesis of type 2 diabetes mellitus (T2DM). Several studies have investigated the effects of genetic polymorphisms in TLR4 and TLR2, but they have yielded limited results. We investigated whether non-missense genetic polymorphisms in the regulatory regions of TLR4 and TLR2 were related to T2DM in a southern Chinese population. Single nucleotide polymorphisms (SNPs) in TLR4 (rs1927911, rs11536889, rs1927907, rs1927906, rs1927914, rs7873784, and rs2149356) and TLR2 (rs1898830, rs3804099, rs4696480, and rs3804100) were genotyped in 552 T2DM and 552 unrelated age- and gender-matched controls by SNaPShot Multiplex assay. Genotypes GG (OR = 0.09, 95%CI = 0.01- 0.83, P = 0.03) and CG (OR = 0.08, 95%CI = 0.01-0.74, P = 0.03) of the 3'-untranslated region (UTR) SNP rs7873784 in TLR4, and genotype AG (OR = 0.67, 95%CI = 0.46-0.97, P = 0.04) and allele G (OR = 0.88, 95%CI = 0.79-0.97, P = 0.01) of the intron SNP rs1898830 in TLR2 were identified as protective against the development of T2DM in southern Chinese people. In contrast, a meta-analysis of rs1927911 and rs1927914 showed no association. Haplotypes AGTT (OR = 0.34, 95%CI = 0.15-0.77, P = 0.01) and AATT (OR = 1.20, 95%CI = 1.01- 1.44, P = 0.05) in TLR2 were significantly associated with susceptibility to T2DM. Our results suggest that the effects of non-missense polymorphisms located in the regulatory regions of TLR4 and TLR2 should not be neglected in T2DM association analysis.

Effects of CD3McAb and rhIL-2 activated bone marrow on the killing and purging of leukemia cells.

We investigated the roles of CD3McAb and rhIL-2 activated bone marrow in the killing and purging of leukemia cells. Cytotoxicity of activated bone marrow was detected with MTT assay. CFU-GM level in activated bone marrow and the destruction of leukemia cells were measured using the semi-solid cell culture. Immune activation markers in activated bone marrow were detected by indirect immunofluorescence assay. Bone marrow activated by CD3McAb and rhIL-2 displayed significantly upregulated the killing and purging abilities on the leukemia cell line K562 and HL-60. Such effects were superior to that of bone marrow activated by rhIL-2 or CD3McAb alone (P < 0.05, P < 0.01). Activation by rhIL-2 and (or) CD3McAb exerted no obvious influence on CFU-GM level in bone marrow. Compared with bone marrow activated by rhIL-2 or CD3McAb alone, the synergistic effect of both CD3McAb+ and hIL-2 caused significant increase of CD3(+), CD8(+), CD19(+), CD25(+), CD38(+), and CD56(+) levels. Our study indicates that CD3McAb enhanced the killing and purging effects of rhIL-2 activated bone marrow on leukemia cells.

Design of vibration compensation interferometer for Experimental Advanced Superconducting Tokamak.

A vibration compensation interferometer (wavelength at 0.532 µm) has been designed and tested for Experimental Advanced Superconducting Tokamak (EAST). It is designed as a sub-system for EAST far-infrared (wavelength at 432.5 µm) poloarimeter/interferometer system. Two Acoustic Optical Modulators have been applied to produce the 1 MHz intermediate frequency. The path length drift of the system is lower than 2 wavelengths within 10 min test, showing the system stability. The system sensitivity has been tested by applying a periodic vibration source on one mirror in the system. The vibration is measured and the result matches the source period. The system is expected to be installed on EAST by the end of 2014.

Faraday-effect polarimeter-interferometer system for current density measurement on EAST.

A multichannel far-infrared laser-based POlarimeter-INTerferometer (POINT) system utilizing the three-wave technique is under development for current density and electron density profile measurements in the EAST tokamak. Novel molybdenum retro-reflectors are mounted in the inside wall for the double-pass optical arrangement. A Digital Phase Detector with 250 kHz bandwidth, which will provide real-time Faraday rotation angle and density phase shift output, have been developed for use on the POINT system. Initial calibration indicates the electron line-integrated density resolution is less than 5 × 10(16) m(-2) (∼2°), and the Faraday rotation angle rms phase noise is <0.1°.

Optical layout and mechanical structure of polarimeter-interferometer system for Experimental Advanced Superconducting Tokamak.

A Far-InfaRed (FIR) three-wave POlarimeter-INTerferometer (POINT) system for measurement current density profile and electron density profile is under development for the EAST tokamak. The FIR beams are transmitted from the laser room to the optical tower adjacent to EAST via ∼20 m overmoded dielectric waveguide and then divided into 5 horizontal chords. The optical arrangement was designed using ZEMAX, which provides information on the beam spot size and energy distribution throughout the optical system. ZEMAX calculations used to optimize the optical layout design are combined with the mechanical design from CATIA, providing a 3D visualization of the entire POINT system.

Characterization of viscoelastic properties of normal and osteoarthritic chondrocytes in experimental rabbit model.

The goal of this study was to characterize the changes of the viscoelastic properties of rabbit chondrocytes from normal and osteoarthritic cartilage. All samples were harvested from rabbit articular cartilage with the same age, sex, body weight, breed and osteoarthritic degree. Anterior cruciate ligament transection was utilized to induce rabbit osteoarthritic model. Micropipette aspiration technique coupled with a viscoelastic model was used to characterize viscoelastic properties of rabbit chondrocytes. The present results indicate that the viscoelastic behaviors of osteoarthritic chondrocytes have decreased during the progress of osteoarthritis and exhibited a significantly lower equilibrium modulus, instantaneous modulus and apparent viscosity (E( proportional, variant)=0.39+/-0.14 kPa, E(0)=0.68+/-0.27 kPa, mu=0.39+/-0.14 kPa.s, n=67) compared with normal chondrocytes (E( proportional, variant)=0.55+/-0.11 kPa, E(0)=0.98+/-0.14 kPa, mu=6.36+/-1.12 kPa.s, n=52) (p<0.0001). These findings may be relevant for chondrocyte-based cartilage tissue engineering.

[TNF-related apoptosis inducing ligand and its research progress on cancer treatment].

TRAIL (TNF-related apoptosis inducing ligand) belongs to the tumor necrosis factor (TNF) cytokine family, can induce apoptosis in a wide variety of tumor cell lines. This review introduces research progress on TRAIL from several aspects: the structure and function of TRAIL, the pathway of its inducing apoptosis, TRAIL and cancer treatment, and its foreground.

Killing effect of TNF-related apoptosis inducing ligand regulated by tetracycline on gastric cancer cell line NCI-N87.

AIM: To clone the cDNA fragment of human TRAIL (TNF-related apoptosis inducing ligand) into a tetracycline-regulated gene expression system, the RevTet-On system, transduce expression vectors into a gastric carcinoma cell line-NCI-N87 and examine the effects of controlled expression of TRAIL in vitro on the gastric carcinoma cells. METHODS: The full-length cDNA of TRAIL was inserted into a vector under the control of the tetracycline-responsive element (TRE) to obtain the plasmid pRevTRE-TRAIL, which was transfected into a packaging cell line PT67. In addition, vector pRev-Tet On and pRevTRE were also transfected into PT67 separately. After hygromycin and G418 selection, the viral titer was determined. The medium containing retroviral vectors was collected and used to transduce a gastric carcinoma cell line NCI-N87. The resulting cell line NCI-N87-Tet On TRE-TRAIL and a control cell line, NCI-N87 Tet On-TRE, were established. TRAIL expression in the cell line was induced by incubating cells with doxycycline (Dox), which is a tetracycline analogue. The killing effect on gastric carcinoma cells was analyzed after induction. RESULTS: The recombinant plasmid pRev-TRE-TRAIL was constructed. After hygromycin or G418 selection, the producer cell lines PT67-TRE, PT67-TRE-TRAIL and PT67-Tet On were obtained,with titers of about 10(8)CFU.L(-1). By transducing NCI-N87 cells with retroviral vectors from these cell lines, stable cell lines NCI-N87-Tet-On TRE-TRAIL (NN3T) and control cell line NCI-N87-Tet-On-TRE (NN2T) were established. The growth curves of the selected cell lines were the same with the wild type NCI-N87. When Dox was added, cell death was obvious in the test groups (29%-77%), whereas no difference was observed in control and wild type cell lines. With the addition of a medium from the test group, human leukemia cell line Jurkat was activated till death (83%), indicating the secretion of active TRAIL proteins from the test cells to the medium. CONCLUSION: With the use of the RevTet-On system, a regulated expression system for TRAIL was constructed. Using this system, the selected killing effect of TRAIL on gastric carcinoma cell line NCI-N87 could be observed.

Lineage-specific regulation of the murine RAG-2 promoter: GATA-3 in T cells and Pax-5 in B cells.

Recombination activating gene-1 (RAG-1) and RAG-2 are expressed in lymphoid cells undergoing the antigen receptor gene rearrangement. A study of the regulation of the mouse RAG-2 promoter showed that the lymphocyte-specific promoter activity is conferred 80 nucleotide (nt) upstream of RAG-2. Using an electrophoretic mobility shift assay, it was shown that a B-cell-specific transcription protein, Pax-5, and a T-cell-specific transcription protein, GATA-3, bind to the -80 to -17 nt region in B cells and T cells, respectively. Mutation of the RAG-2 promoter for Pax-5- and GATA-3-binding sites results in the reduction of promoter activity in B cells and T cells. These results indicate that distinct DNA binding proteins, Pax-5 and GATA-3, may regulate the murine RAG-2 promoter in B and T lineage cells, respectively. (Blood. 2000;95:3845-3852)

Crystal structure determination of mung bean trypsin inhibitor Lys fragment-bovine trypsin complex--molecular replacement, electron density map at 3.0 angstron resolution.

The orientation and position of the trypsin molecule in the complex crystal cell mung bean trypsin inhibitor Lys fragment (MBILF)-bovine trypsin (BTRY) have been successfully determined by molecular replacement method with the model of the refined bovine trypsin molecule. Starting from the BTRY coordinates which were oriented and located in the correct azimuth and position in the complex cell according to the result from rotation function and translation function, sim-weighted Fourier map with coefficients 2/Fo/-/Fc/ at 3.0 A resolution was calculated. Besides the electron density which is obviously attributed to itself, in the vicinity of the active site of BTRY the dense contour levels corresponding to the MBILF and and its boundary could be clearly seen in this map. The size of MBILF was approximately estimated at 15 x 15 x 25 A.