Circulating cytokines and alcoholic liver disease: a two-sample bidirectional Mendelian randomization study.

BACKGROUND: Increased inflammation in the liver during ethanol exposure is a major feature of alcoholic liver disease (ALD). An important contributing component to the development of ALD is the inflammatory response brought on by immunological response, however the connection between individual circulating cytokines and ALD is still unclear. To ascertain the causation, we conducted a two-sample bidirectional Mendelian randomization research. METHODS: We extracted 41 cytokines and growth factors of 8293 Europeans and ALD cases of the same ethnicity (1416 cases and 217,376 controls) from the Genome-Wide Association Studies (GWAS) database for two-sample bidirectional MR analysis. RESULTS: Our analyses suggest that higher interleukin-7 (IL-7) levels are associated with an increased risk of ALD (p = 0.028, OR = 1.191,95% CI = 1.019-1.392), while tumor necrosis factor related apoptosis inducing ligand (TRAIL) is a protective factor for ALD (p = 0.032, OR = 0.863, 95% CI = 0.754-0.988) which can reduce the risk of disease occurrence. In addition, genetically predicted ALD does not affect the expression of circulating cytokines regulators. CONCLUSIONS: Our study supports that cytokines play a pivotal role in the pathogenesis of ALD. To determine the mechanisms and pathways of action of these biomarkers, further basic research is required to ensure their clinical suitability for preventing and treating ALD.

Population pharmacokinetics of free and liposome-encapsulated mitoxantrone in patients with relapsed/refractory lymphoma or small cell lung cancer.

OBJECTIVE: This study is aimed at investigating the pharmacokinetic (PK) characteristics of pegylated liposomal mitoxantrone (PLM) in patients with relapsed/refractory lymphoma or small cell lung cancer (SCLC) by constructing population pharmacokinetic (popPK) models for both liposome-encapsulated mitoxantrone and free mitoxantrone. METHODS: A total of 23 patients with relapsed/refractory lymphoma and 42 patients with SCLC were included. A popPK model was simultaneously developed utilizing a non-linear mixed effects model (NONMEM) to explore the PK profiles of liposome-encapsulated mitoxantrone and free mitoxantrone. Clearance (CL) and distribution volume (V) were calculated, and covariate analysis was employed to evaluate the influence of patient disease type, demographic information, and biochemical indicators of liver and kidney function on PK parameters. RESULTS: The concentration-time profiles for both liposome-encapsulated mitoxantrone and free mitoxantrone were described by a one-compartment model. The release (Rel) of liposome-encapsulated mitoxantrone to free mitoxantrone was determined to be 0.0191 L/h, and the V of liposome-encapsulated mitoxantrone was 2.32 L. The apparent CL of free mitoxantrone was estimated at 1.66 L/h. The apparent V of free mitoxantrone was 35.8 L in patients with relapsed/refractory lymphoma and 22.2 L for patients with SCLC. In patients with relapsed/refractory lymphoma, lower maximum concentration (Cmax) and higher apparent V of free mitoxantrone were observed compared with patients with SCLC. CONCLUSION: The popPK characteristics of both liposome-encapsulated and free mitoxantrone in patients with relapsed/refractory lymphoma or SCLC were effectively described by a one-compartment model.

Exploring the effect of Wuzhi capsule on the pharmacokinetics of regorafenib and its main metabolites in rat plasma using liquid chromatography-tandem mass spectrometry.

Regorafenib is a small-molecule tyrosine kinase inhibitor with severe hepatotoxicity. It undergoes metabolism mainly by CYP3A4 to generate active metabolites regorafenib-N-oxide (M2) and N-desmethyl-regorafenib-N-oxide (M5). Wuzhi capsule (WZC) is an herbal preparation derived from Schisandra sphenanthera and is potentially used to prevent regorafenib-induced hepatotoxicity. This study aims to explore the effect of WZC on the pharmacokinetics of regorafenib in rats. An efficient and sensitive liquid chromatography-tandem mass spectrometry method was developed to quantitatively determine regorafenib and its main metabolites in rat plasma. The proposed method was applied to the pharmacokinetic study of regorafenib in rats, with or without WZC. Coadministration of regorafenib with WZC resulted in a prolonged mean residence time (MRT) of the parent drug but had no statistically significant difference in other pharmacokinetic parameters. While for the main metabolites of regorafenib, WZC decreased the area under the curve and maximum concentration (Cmax ), delayed the time to reach Cmax , and prolonged the MRT of M2 and M5. These results indicate that WZC delayed and inhibited the metabolism of regorafenib to M2 and M5 by suppressing CYP3A4. Our study provides implications for the rational use of the WZC-regorafenib combination in clinical practice.

Identification and Validation of the Diagnostic Markers for Inflammatory Bowel Disease by Bioinformatics Analysis and Machine Learning.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract which is mediated by the inappropriate immune responses. This study was aimed to identify novel diagnostic biomarkers for diagnosis of IBD and explore the relationship between the diagnostic biomarkers and infiltrated immune cells. GSE38713, GSE53306, and GSE75214 downloaded from the Gene Expression Omnibus (GEO) database were split into training and testing sets. Differentially expressed genes (DEGs) were screened using the "limma" package. Gene Ontology (GO) and KEGG pathway enrichment analysis of DEGs were performed by clusterProfiler package. The LASSO regression and support vector machine recursive feature elimination (SVM-RFE) algorithms were conducted to identify novel diagnostic biomarkers. The receiver operating characteristic (ROC) curve was applied to evaluate the diagnostic value of the candidate biomarkers. The relationship of the candidate biomarkers and infiltrating immune cells in IBD were evaluated by CIBERSOTR. Quantitative Real-Time PCR (qRT-PCR) was applied to measure the expression level of the biomarkers in IBD. A total of 289 dysregulated genes were identified as DEGs in IBD. These DEGs were significantly enriched in chemokine signaling pathway and cytokine-cytokine receptor interaction. RHOU was identified as a critical diagnostic gene in IBD, which was confirmed using ROC curve and qRT-PCR assays. Immune cell infiltration analysis showed that RHOU was correlated with macrophages M2, dendritic cells resting, mast cells resting, T cells CD4 memory resting, macrophages M0, and mast cells activated. Our results imply that RHOU may be a potential diagnostic biomarker for IBD.

11B NMR of the Morphological Evolution of Traditional Chinese Medicine Borax.

This article applies nuclear magnetic resonance technology to the study of boron-containing traditional Chinese medicine, in order to explore the morphological evolution of boron elements in traditional Chinese medicine. Borax is a traditional Chinese medicine with anti-corrosion, anti-inflammatory, antibacterial, and anticonvulsant effects. It is made by boiling, removing stones, and drying borax minerals like borate salts. This article introduces an 11B nuclear magnetic resonance method for identifying and characterizing boron-containing compounds in TCM. We applied this technology to borax aqueous solutions in different chemical environments and found that with boron mixed in the form of SP2 hybridization in equilateral triangles and SP3 hybridization in equilateral tetrahedra, the pH changes in alkaline environments significantly affected the ratio of the two. At the same time, it was found that in addition to the raw material peak, boron signals of other boron-containing compounds were also detected in 20 commercially available boron-containing TCM preparations. These new boron-containing compounds may be true pharmaceutical active ingredients, and adding them directly to the formula can improve quality and safety. This article describes the detection of 11B NMR in boron-containing traditional Chinese medicine preparations. It is simple, non-destructive, and can provide chemical fingerprint studies for boron-containing traditional Chinese medicine.

Stress Induces Prolonged Pain Recovery After Surgery: Involvement of Glucocorticoid-Related Pathway.

BACKGROUND: Increasing evidence suggests that chronic stress increases pain sensitivity and exacerbates existing pain. However, whether and how chronic unpredictable stress (CUS) affects surgical pain is unclear. METHODS: A postsurgical pain model was performed by longitudinal incision from 0.3 cm of the proximal edge of the heel toward the toes. The skin was sutured, and the wound site was covered. Sham surgery groups underwent the same procedure without an incision. The short-term CUS procedure was conducted by exposure of mice to 2 different stressors each day for 7 days. The behavior tests were conducted between 9:00 am and 4:00 pm. Mice were killed on day 19, and the mouse bilateral L4/5 dorsal root ganglia, spinal cord, anterior cingulate and insular cortex, and amygdala were collected for immunoblot analyses. RESULTS: Presurgical exposure of mice to CUS every day for 1-7 days showed significant depression-like behavior as evidenced by reduced sucrose preference in the sucrose consumption test and prolonged immobility time in the forced swimming task. This short-term CUS procedure did not affect the basal nociceptive response to mechanical and cold stimuli in the Von Frey and acetone-induced allodynia tests, but it delayed pain recovery after surgery, as indicated by the prolonged hypersensitivity in mechanical and cold stimuli by 12 days. The subsequent studies demonstrated that this CUS caused an increase in adrenal gland index. The abnormalities in pain recovery and adrenal gland index after surgery were reversed by a glucocorticoid receptor (GR) antagonist RU38486. Moreover, the prolonged pain recovery after surgery induced by CUS seemed to involve an increase in GR expression and decreases in cyclic adenosine monophosphate, phosphorylated cAMP response element binding protein, and brain-derived neurotrophic factor levels in emotion-related brain regions, such as anterior cingulate and insular cortex, amygdala, dorsal horn, and dorsal root ganglion. CONCLUSIONS: This finding indicates that stress-induced GR change may result in dysfunction of GR-related neuroprotective pathway.

Proteomic profiling identifies novel diagnostic biomarkers and molecular subtypes for mucinous tubular and spindle cell carcinoma of the kidney.

Mucinous tubular and spindle cell carcinoma (MTSCC) is a relatively rare renal epithelial neoplasm resembling type 1 papillary renal cell carcinoma (PRCC) morphologically and immunohistochemically. The accurate diagnosis of MTSCC remains a challenge. Here, by using proteomic profiling, we characterized MTSCC and PRCC to identify diagnostic biomarkers. We found that the MTSCC tumor proteome was significantly enriched in B-cell-mediated immunity when compared with the proteome of adjacent normal tissues of MTSCC or tumors of PRCC. Importantly, we identified MZB1, VCAN, and SOSTDC1 as diagnostic biomarkers to distinguish MTSCC from the solid variant of type 1 PRCC, with an AUC of 0.985 when combined. MZB1 was inversely correlated with tumor clinical stage and may play an anti-tumor role by activating the complement system. Finally, unsupervised clustering revealed two molecular subtypes of MTSCC, displaying different morphology, expression signatures of oxidative phosphorylation, and aggravation. In summary, our analyses identified a three-protein diagnostic panel and molecular subtypes for MTSCC. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Phase wavefront perturbation calculation model for spectroscopic refractive index matching of hybrid materials.

A low-cost flexible spectroscopic refractive index matching (SRIM) material with bandpass filtering properties without incidence angle and polarization dependence by randomly dispersing inorganic C a F 2 particles in organic polydimethylsiloxane (PDMS) materials was proposed in our previous study. Since the micron size of the dispersed particles is much larger than the visible wavelength, the calculation based on the commonly used finite-difference time-domain (FDTD) method to simulate light propagation through the SRIM material is too bulky; however, on the other hand, the light tracing method based on Monte Carlo theory in our previous study cannot adequately explain the process. Therefore, a novel approximate calculation model, to the best of our knowledge, based on phase wavefront perturbation is proposed that can well explain the propagation of light through this SRIM sample material and can also be used to approximate the soft scattering of light through composite materials with small refractive index differences, such as translucent ceramics. The model simplifies the complex superposition of wavefront phase disturbances and the calculation of scattered light propagation in space. The scattered and nonscattered light ratios; the light intensity distribution after transmission through the spectroscopic material; and the influence of absorption attenuation of the PDMS organic material on the spectroscopic performance are also considered. The simulation results based on the model are in great agreement with the experimental results. This work is important to further improve the performance of SRIM materials.

Selective removal of aqueous Hg2+ by magnetic composites sulfur-containing on the hyper-branched surface: Characterization, performance and mechanism.

The adsorbents with recyclable, large adsorption capacity and selective adsorption can effectively remove the pollution and harm of heavy metal ions in water. Therefore, two magnetic composites containing sulfur (MCP-S4 and MCP-S8) on the hyper-branched surface were prepared, furthermore, their structures were characterized and adsorption performance was analyzed by FTIR, XRD, TGA, BET, SEM, TEM, VSM and ICP. The results showed that both MCP-S4 and MCP-S8 had superparamagnetism with saturation susceptibility of 22.10 and 22.26 emu/g, and owned a specific surface area of 11.394 and 11.235 m2/g, respectively. MCP-S4 and MCP-S8 could selectively adsorb Hg2+ with the exist of Fe3+, Cu2+, Co2+, Ni2+, Mn2+, and Al3+ in solution. The adsorption kinetics accorded with pseudo-second-order model and Boyd film diffusion model, and the adsorption isotherm was fitted better with Langmuir isotherm model and D-R model, furthermore, the adsorption was an entropic-increasing and endothermic process. The removal rate of Hg2+ from simulated sewage by the two materials was more than 91%, and the adsorption retention rate was more than 85% after five adsorption-desorption cycles. The adsorption mechanism was analyzed by comparing the changes of FTIR, EDS and XPS spectra before and after adsorption. It was found that functional groups (C-N, CONH, CS, SH) could form stable chelates with Hg2+, which was the main reason why MCP-S4 and MCP-S8 could adsorb Hg2+ selectively, furthermore, S atoms of CS and -SH played a leading role in the process of adsorption. In addition, DFT calculation was also used as an auxiliary means to verify the adsorption mechanism.

METAGENOMIC NEXT-GENERATION SEQUENCING DETECTS PATHOGENS IN ENDOPHTHALMITIS PATIENTS.

PURPOSE: To investigate the utility of metagenomic next-generation sequencing (mNGS) in identifying the pathogens in endophthalmitis. METHODS: In this prospective study, 36 cases of endophthalmitis were recruited. All patients received surgical treatment and intraocular drug lavage. The samples of vitreous or aqueous humor were extracted for mNGS and microbiological culture. The diagnostic performance of pathogens was compared between mNGS and culture. RESULTS: The positive rates of mNGS and culture were 88.89% (32/36) and 27.78% (10/36), respectively. There was a statistically significant difference between mNGS and culture (Chi-square = 27.657; P < 0.01). Staphylococcus epidermidis, Streptococcus pneumoniae, and Klebsiella pneumoniae were the most pathogenic bacteria in traumatic, postoperative, and endogenous endophthalmitis, respectively. The concordance of pathogen identified by mNGS and culture was 70% for culture-positive cases. Antibiotic resistance genes were identified in 9 cases. There was a marginal correlation between the final visual acuity and the microbial sequence read (Spearman correlation coefficient = 0.498; P = 0.05). CONCLUSION: Metagenomic next-generation sequencing has a higher positive rate of identifying pathogens in endophthalmitis than in culture. It can also provide information on antibiotic resistance and visual prognosis. However, caution must be taken when interpreting the results of mNGS because they may not be concordant with culture.

Matrine exerted an anti-tumor effect on acute myeloid leukemia via the lncRNA LINC01116/miR-592-mediated JAK/STAT pathway inactivation.

As a malignant hematological cancer, acute myeloid leukemia (AML) influences the health of many people. This study explored the anti-AML activity of matrine (a natural-derived alkaloid), as well as the internal molecular mechanism. In vitro, cell viability, apoptosis, and productions of inflammatory cytokines including IL-1ß, IL-6, and TNF-α were tested by MTT, Annexin V-FITC/PI staining, and ELISA, respectively. The expression levels of LINC01116 and miR-592 were measured by qRT-PCR. Bcl-2 and PCNA expression, and JAK/STAT3 pathway activity were evaluated by western blotting. Besides, an AML mouse xenograft model was established to further analyze the anti-AML activity of matrine. We found that matrine suppressed cell proliferation and levels of inflammatory factors, induced cell apoptosis, reduced LINC01116 expression, and raised miR-592 expression in AML cells. LINC01116 directly bound to miR-592 and downregulated its expression. Both LINC01116 overexpression and miR-592 knockdown attenuated the effects of matrine on AML cells. Moreover, miR-592 overexpression reversed the influences of LINC01116 overexpression on matrine-treated AML cells. Matrine inactivated the JAK/STAT3 pathway in AML cells via modulating LINC01116/miR-592. Additionally, matrine inhibited tumor growth via modulating LINC01116/miR-592 in vivo. To sum up, matrine exhibited the anti-AML activity through regulating the LINC01116/miR-592 axis, thereby inactivating the JAK/STAT3 pathway.

Periacetabular osteotomy with or without femoral osteotomy for the treatment of hip subluxation in children and young adults with cerebral palsy.

BACKGROUND: This study is aimed to investigate retrospectively the radiographic and clinical outcomes in children and young adults with cerebral palsy (CP) undergoing periacetabular osteotomy (PAO) with or without femoral osteotomy (FO) for hip subluxation. METHODS: A consecutive cohort of twenty-one patients (23 hips) with symptomatic CP hip subluxation were treated with PAO with or without FO and reviewed retrospectively. Two patients (2 hips) were excluded due to insufficient follow-up and lost to follow-up, respectively. The Reimers migration percentage, lateral center-edge angle (LCEA), Sharp angle, neck-shaft angle (NSA), femoral anteversion (FNA), Gross Motor Function Classification System (GMFCS) and hip pain were assessed. RESULTS: Twenty-one hips (19 patients) with CP treated with PAO with or without FO were included. Five hips received PAO. Sixteen hips underwent PAO with FO. Mean age at surgery was 19 ± 6 and 15 ± 4 years for PAO and PAO plus FO, respectively. Mean follow-up was 44.0 ± 28.3 months for PAO and 41.5 ± 17.2 months for PAO + FO. All hips were painful before surgery and painless at final visits. The GMFCS improved by one level in 10 of 19 patients. There was significant increase in LCEA (p < 0.001) and decrease in the Reimer's MP (p < 0.001), NSA (p < 0.001) and Tonnis angle(p < 0.001) postoperatively. Resubluxation occurred in 7 hips (30%) due to insufficient correction and loosening of fixation. Nervus cutaneus femoris lateralis was impaired in 4 patients after surgery. There was no avascular necrosis of the femoral head, resubluxation or infection. CONCLUSION: PAO with or without FO can be effective for children and young adults with concomitant hip subluxation and CP.

Characteristics of the patellofemoral joint of patients with DDH and the effects of Bernese periacetabular osteotomy on the patellofemoral joint.

BACKGROUND: Some patients with developmental dysplasia of the hip (DDH) complained of anterior knee pain (AKP) before and after Bernese periacetabular osteotomy (PAO) surgery. The purpose of this study was to (1) identify the characteristics of patellofemoral joint (PFJ) deformities in patients with DDH and (2) to determine the effects of PAO on the PFJ. METHODS: Seventy patients (86 hips) were included in the DDH group. Thirty-three patients (33 knees) without AKP and hip pain were included in the control group. All patients underwent simultaneous CT scans of the hip and knee joints before PAO and after hardware removal surgery. The distance from the anterior inferior iliac spine to the ilioischial line (DAI), was measured in DDH patients. Imaging parameters of knees, including the sulcus angle (SA), femoral trochlear depth (FTD), patellar width (PW), tibial tuberosity-trochlear groove (TT-TG), patellar tilt angle (PTA) and lateral shift of the patella (LSP) were measured in patients in both the DDH and control group. TT-TG, PTA, and LSP of DDH patients were measured before PAO and after hardware removal. The DAI, PTA, LSP and TT-TG of all DDH patients before and after Bernese PAO were compared using paired t-tests. The FTD, PW, and SA of the DDH patients and the control group were analyzed using independent t-tests. PTA, TT-TG, and LSP between the control group and preoperative DDH patients, between the control group and post PAO patients were compared using independent t-tests. RESULTS: The DAI changed from 4.04 ± 0.61 mm before PAO surgery to 5.44 ± 0.63 mm after PAO surgery. The SA of the DDH group (140.69 ± 11.30 degree) was greater than that of the control group (130.82 ± 6.43 degree). The FTD and the PW of the DDH group (5.45 ± 1.59 mm, 4.16 ± 0.36 mm) were smaller than that of the control group (7.39 ± 1.20 mm, 4.24 ± 0.38 mm). The changes in LSP, PTA, and TT-TG before and after surgery were not statistically significant. Both before and after PAO, there was no statistically significant difference in the parameters of LSP, PTA, and TT-TG compared with the control group. CONCLUSION: The knee joints of DDH patients presented a certain degree of femur trochlear groove dysplasia and patellofemoral instability. PAO surgery did not change PFJ stability, although the origination point of the rectus femoris muscle moved laterally during PAO surgery.

What is the agreement between intraoperative fluoroscopy and postoperative radiographs in Bernese periacetabular osteotomy?

BACKGROUND: It is important to reorient the acetabular fragment into an optimal position and version to ensure a good long-term outcome after Bernese periacetabular osteotomy (PAO). Unfortunately, the intraoperative balance between overcorrection and undercorrection remains challenging for the surgeon. The purpose of this study was to answer two questions: (1) Does the femoral head coverage measured on intraoperative fluoroscopy agree with that measured on postoperative radiography? (2) What is the reliability of intraoperative fluoroscopy in identifying hip center correction in PAO? METHODS: A total of 173 patients (173 hips) who underwent PAO for developmental dysplasia of the hip (DDH) at our center from July 01, 2020, to December 31, 2020, were retrospectively reviewed. Imaging data from 111 patients (female/male, 98/13; right/left, 72/39; mean age, 28.93 years) were included in this study. The analysis included measurement of the lateral center-edge angle (LCEA), acetabular index (AI), anterior wall index (AWI), posterior wall index (PWI), extrusion index (EI), and medial offset distance (MO). These measurements were acquired from intraoperative fluoroscopic images and postoperative radiographs and compared by paired t test using SPSS (version 24.0). Significance was determined at a p value of < 0.05. Bland-Altman analysis, conducted using GraphPad Software (version 9), was used to quantify the agreement between intraoperative fluoroscopic images and postoperative radiographs. RESULTS: The means (standard deviations, SDs) of the LCEA, AI, AWI, PWI, EI, and MO obtained on intraoperative fluoroscopy were 32.86° (5.73°), 0.66° (5.55), 0.29 (0.10), 0.75 (0.17), 11.15% (6.50%), and 8.49 mm (3.68 mm), respectively. On postoperative radiography, the corresponding values were 32.91° (6.31°), 1.63° (5.22°), 0.29 (0.15), 0.85 (0.14), 11.27% (7.36%), and 9.60 mm (3.79 mm). The differences in the LCEA, AWI, and EI acquired from intraoperative fluoroscopic images and postoperative radiographs were not significant (p = 0.90, 0.95, and 0.83, respectively), but those in the AI, PWI, and MO were significant (p < 0.05). The mean biases (95% limits of agreement) of the LCEA, AI, AWI, PWI, EI, and MO were - 0.04 (- 6.85), - 0.97 (- 7.78), 0 (- 0.30), - 0.11 (- 0.36), - 0.12 (- 11.92), and - 1.11 (- 5.51), respectively. CONCLUSION: The LCEA, EI, and AWI can be used to reliably predict postoperative femoral head coverage at the level of 2D graphics. Acetabular inclination can be cautiously assessed using AI on intraoperative fluoroscopy. In the absence of intraoperative 3D image evaluation, the AWI and PWI demonstrate acceptable agreement between fluoroscopy and radiography in assessing the acetabular version. Although the MO shows slight bias, it can be helpful in properly positioning the acetabulum during PAO.

Variations in lower limb alignments indicate pelvic tilt after total hip arthroplasty.

OBJECTIVE: We sought to correlate various spinopelvic and lower limb alignments, and to examine the current spinopelvic theories on a Chinese cohort. METHODS: We retrospectively reviewed 166 patients undergoing THA. Among them, 138 patients with unilateral THA met the inclusion criteria. Sagittal alignments and cup orientations were measured on standing and sitting lateral EOS images. Patients were categorized into two groups with a scoring system for lumbar spine degeneration. Patients' demographics including age, sex, lumbar spine degeneration and radiographic measurements were studied. RESULTS: PT, SS, LL and TK differed significantly between standing and sitting within each group except for TK in degenerative group (32.8 ± 13.9 vs. 32.9 ± 14.2, p = 0.905). Compared with degenerative spine group, non-degenerative spine patients have great pelvic mobility (ΔPT, -24.4 ± 12.5° vs. -17.6 ± 10.7, p = 0.0008), greater lumbar mobility (ΔLL, -34.8 ± 15.2 vs. -21.7 ± 12.2, p = < 0.0001) and compensatory cup orientation changes (ΔRA, -15.5 ± 11.1 vs. -12.0 ± 8.4, p = 0.00920; ΔRI, -10.8 ± 11.5 vs. -5.6 ± 7.5, p = 0.0055). Standing PT and ankle dorsiflexion angle correlated positively (R2 = 0.236, p = 0.005). CONCLUSION: THA patients in this cohort showed a spinopelvic motion paradigm similar to that from previous studies on Caucasians. Ankle dorsiflexion indicate greater posterior pelvic tilt on standing. Surgeons should beware of risks of instability in patients with lower limb compensations. ADVANCES IN KNOWLEDGE: This study provides new insights into the clinical relevance of lower limb alignments to spinopelvic motion after THA in a relatively young Chinese population.

Low-Frequency Vibrational Spectroscopy Characteristic of Pharmaceutical Carbamazepine Co-Crystals with Nicotinamide and Saccharin.

The pharmaceutical co-crystal has attracted increasing interest due to the improvement of physicochemical properties of active pharmaceutical ingredients. The characterization of pharmaceutical co-crystal is an integral part of the pharmaceutical field. In this paper, the low-frequency vibrational properties for carbamazepine co-crystals with nicotinamide and saccharin (CBZ-NIC and CBZ-SAC) have been characterized by combining the THz spectroscopy with low-wavenumber Raman spectroscopy. The experiment results show that, compared with the individual constituents, CBZ-NIC and CBZ-SAC co-crystals not only have different characteristic absorption peaks in the 0.3-2.5 THz region, but also have significant low-wavenumber Raman characteristic peaks in 0-100 cm-1. Density functional theory was performed to simulate the terahertz and low-wavenumber Raman spectra of the two co-crystals, where the calculation agreed well with the measured vibrational peak positions. The vibrational modes of CBZ-NIC and CBZ-SAC co-crystals were assigned through comparing theoretical results with the experimental spectra. Meanwhile, the low-frequency infrared and/or Raman active of characteristic peaks for such co-crystals were discussed. The results indicate the combination of THz spectroscopy and low-wavenumber Raman spectroscopy can provide more comprehensive low-frequency vibrational information for pharmaceutical co-crystals, such as collective vibration and skeleton vibration, which could play an important role in pharmaceutical science.

Selective adsorption of heavy metals from water by a hyper-branched magnetic composite material: Characterization, performance, and mechanism.

The development of adsorbents to remove heavy metal ions from water with recyclable, high adsorption capacity, strong selectivity, safe, and economic performances has always been the focus and challenge of current research. A hyper-branched magnetic composite material (Fe3O4@SiO2-S4) was fabricated by a method combining "grafting,", "branching," and "modification,", and the structure was characterized by FTIR, XRD, SEM, TEM, SAED, VSM, TGA, and BET. In addition, the adsorption performance and mechanism for heavy metal ions in water were studied. The as-prepared composite material had excellent selective absorbability for Hg2+, Cd2+, and Ag+ in the presence of Fe3+, Fe2+, Cu2+, Mn2+, CO2+, Zn2+, and Ni2+, and when pH = 6, T = 30 °C, t = 4 h, it reached a saturated adsorption capacity of 2.42, 2.18, and 1.94 mmol/g to Hg2+, Cd2+, and Ag+, respectively. The adsorption isotherm was consistent with the Langmuir isotherm adsorption model, and the Dubinin Redushcke (D-R) model identified that the adsorption was chemical adsorption in nature. The adsorption kinetic followed the pseudo-second-order model and Boyd film diffusion models. The adsorption capacity of as-prepared material remained about 83% after five elutions. The adsorption mechanism and selective adsorption were revealed by FTIR, EDS, XPS, and DFT calculation. N atoms and O atoms of the active functional groups complexed with metal ions to form stable 2 heptachate chelates and 1 tridentate chelate to achieve the effect of adsorption; furthermore, the adsorption was mainly governed by N atoms of Schiff base groups. This work not only explored an innovative method for the construction of adsorbing materials but also provided a promising adsorbent to selectively remove heavy metal ions in water with potential application.

Spectrum-Effect Relationship-Based Strategy Combined with Molecular Docking to Explore Bioactive Flavonoids from Sceptridium ternatum.

Sceptridium ternatum is a herbaceous plant with significant potential for pharmaceutical and cosmetic applications. In this study, we established a spectrum-effect relationship-based strategy to investigate the bioactive basis and tissue distribution in S. ternatum. First, a phytochemical analysis on the ethanol extracts from roots, stems, and leaves of S. ternatum was performed using the colorimetric method, high-performance liquid chromatography-ultraviolet (HPLC-UV), and high-performance liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-Q-TOF-MS/MS). Then, radical scavenging assays and the lipopolysaccharide-stimulated RAW 264.7 cell model were used to estimate the antioxidant and anti-inflammatory activities, respectively. Spectrum-effect relationship analysis and molecular docking were further employed to evaluate the correlation between the phytochemical profile and anti-inflammatory activity. Our results demonstrate that S. ternatum leaves contained the most abundant flavonoids and exerted the best biological activities. Their IC50 values for scavenging 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) and 1,1-diphenyl-2-picrylhydrazyl radicals were 2.43 ± 0.13 and 5.36 ± 0.54 mg/mL, respectively. In lipopolysaccharide-stimulated RAW 264.7 cells, the leaf extract caused the greatest reduction in nitric oxide production (38.15%) and interleukin-6 release (110.86%). Spectrum-effect relationship analysis and molecular docking indicated that quercetin 3-O-rhamnoside-7-O-glucoside possessed high anti-inflammatory activity by binding with interleukin-6. In conclusion, S. ternatum is a rich source of bioactive flavonoids with potential for exploitation in the prevention and treatment of oxidative stress and inflammation-related pathologies.

The preparation of polyclonal antibody against chlordimeform and establishment of detection by indirect competitive ELISA.

Objective: Chlordimeform is a chemical pesticide that is highly carcinogenic and toxic. The purpose of this study was to establish an enzyme-linked immunosorbent assay (ELISA) method for the detection of chlordimeform in aquaculture and fish farming. METHODS: Chlordimeform was coupled with bovine serum albumin (BSA) and ovalbumin (OVA) as carrier proteins. A chlordimeform-BSA conjugate was used as an immunogen, and chlordimeform-OVA was used as a coating antigen. Chlordimeform-BSA was used to immunize rabbits, and a polyclonal antibody was prepared. An indirect competitive enzyme-linked immunosorbent assay (IC-ELISA) was established to detect chlordimeform. RESULTS: The working range of the established IC-ELISA method for chlordimeform detection was 1-20 ng/mL. The IC50 was 3.126 ng/mL, and the lower limit of detection (LOD) of chlordimeform was 0.637 ng/mL. The recovery of chlordimeform from spiked water samples ranged from 81% to 107%. CONCLUSION: An anti-chlordimeform polyclonal antibody was successfully developed, and a novel IC-ELISA was established to detect chlordimeform in aquaculture.

Alterations in the gut microbiota and metabolic profiles coincide with intestinal damage in mice with a bloodborne Candida albicans infection.

Candida albicans is an opportunistic fungus that can threaten life especially in patients with candidemia. The morbidity and mortality of candidemia originating from a central venous catheter (CVC) and illicit intravenous drug use (IVDU) are increasing. However, the mechanism underlying the bloodborne C. albicans infection remains unclear. Herein, we evaluated the gut microbiome, metabolites and intestinal mucosa by constructing the mouse models with candidemia. Model mice were injected with C. albicans via tail vein. Control mice underwent sham procedures. We observed basic life characteristics, intestinal damage-related alterations using hematoxylin and eosin (H&E) staining, intestinal tight junction protein levels, and intestinal permeability in these mice. Fecal samples were analyzed by performing 16S rRNA gene sequencing of the microbiota and LC-MS metabolomics to reveal the perturbations in intestinal flora and metabolism exacerbating intestinal damage. Weight loss, a decreased survival rate, C. albicans infection spread, and colonic epithelial damage occurred in the model group. Furthermore, the intestinal flora abundance was reduced. Several probiotics, such as Lactobacillus, and butyrate-producing bacteria, including Roseburia, Lachnospiraceae, and Clostridia, were depleted, and some pathogenic bacteria, such as Escherichia-Shigella and Proteus, belonging to the Proteobacteria phylum, and the inflammation mediators Ruminococcus and Parabacteroides were enriched in model mice. Multiple differentially altered metabolic pathways were observed and mainly related to bile acid, arachidonic acid, bile secretion, and arachidonic acid metabolism. This study illustrated the effects of a bloodborne C. albicans on the intestinal microbiota, metabolites, and intestinal barrier, which may provide new insights into tests or treatments for candidemia originating from CVC or IVDU.