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Objective: To investigate the clinical effect of total hip replacement (THA) in the treatment of traumatic arthritis secondary to acetabular fracture., Methods: From October 2019 to June 2022, 15 patients with secondary traumatic arthritis of acetabulum fracture were treated with THA. There were 8 males and 7 females, aged from 40 to 76 years old with an average of (59.20±9.46) years old. Prosthesis loosening, dislocation of hip joint, range of motion of hip joint, nerve injury and other conditions were recorded before and after surgery. Harris score, visual analogue scale (VAS) and imaging were used to evaluate hip joint function and surgical effect., Results: Follow-up time ranged 6 to 39 months with an average of (18.33±9.27) months. All the 15 patients successfully completed the operation, no nerve and blood vessel injury during the operation, postoperative wound healing was stageⅠ, no infection, one case of acetabular side prosthesis loosening at half a year after operation, and recovered well after revision surgery, one case of hip dislocation was cured after open reduction treatment, no adverse consequences. Harris score at the last postoperative follow-up was (88.60±4.01) points, compared with the preoperative (47.20±11.77) points, the difference was statistically significant ( P <0.05), and VAS at the lateat postoperative follow-up was 1 (1) points, compared with the preoperative 8 (2) points, the difference was statistically significant ( P <0.05). At the last follow-up, the pain symptoms were relieved or disappeared, and the joint function was satisfactory. The imaging data of the latest follow-up showed joint was well pseudoradiated, no abnormal ossification occurred, and the prosthesis was not loose., Conclusion: THA is effective in the treatment of traumatic arthritis secondary to acetabular fracture and can effectively improve the quality of life of patients. Preoperative comprehensive evaluation and bone defect evaluation of patients, and intraoperative management of acetabulum, femur, internal fixation and bone defect are key factors for the success of surgery.

Background: Clonorchis sinensis (CS) is classified as a group 1 carcinogen and can cause intrahepatic cholangiocarcinoma (ICC). CS extracellular vesicles (CsEVs) play important roles in mediating communication between parasitic helminths and humans. Ferroptosis is a novel cell death mechanism that is mainly induced by lipid peroxidation and iron overload. However, the role of CsEVs in the regulation of ferroptosis in ICC remains unclear. This study aimed to explore the role of CS-secreted miR-96-5p (csi-miR-96-5p) delivered by CsEVs in ICC progression and ferroptosis., Methods: Tissue samples were collected from ICC patients with CS infection (CS-ICC) or without CS infection (NC-ICC). The levels of csi-miR-96-5p and PTEN gene were determined by quantitative polymerase chain reaction (qPCR) and western blotting, and survival analysis was performed. CsEVs were isolated and identified by ultracentrifugation and transmission electron microscopy. Lentiviruses were used to establish stable cell lines with csi-miR-96-5p mimic expression, PTEN overexpression (PTEN-EXO) and PTEN CRISPR/Cas9-based knockout (PTEN-KO) and their respective negative controls. Cell proliferation was assessed by performing Cell Counting Kit-8 assays in vitro and in a tumor xenograft model in vivo, and cell migration was assessed by performing Transwell assays. Erastin is used to induce ferroptosis. Ferroptosis levels were evaluated using biomarkers., Results: High csi-miR-96-5p and low PTEN expression was observed in CS-ICC tissues and was associated with poor overall survival. csi-miR-96-5p was highly enriched in CsEVs and was taken up by ICC cells. csi-miR-96-5p mimics or PTEN-KO significantly promoted the growth and migration of ICC cells in vitro and in vivo, whereas PTEN-EXO exerted the opposite effect. Mechanistically, csi-miR-96-5p mimics or PTEN-KO inhibited erastin-induced ferroptosis, including reducing the accumulation of Fe 2+ , lipid reactive oxygen species, and malondialdehyde, increasing the GSH/GSSG ratio and levels of SLC7A11 and GPX4, whereas PTEN-EXOs exerted the opposite effect., Conclusions: csi-miR-96-5p delivered by CsEVs reduced ferroptosis by regulating the expression of the PTEN/SLC7A11/GPX4 axis, thereby promoting ICC proliferation and migration. For the first time to our knowledge, we found that CS miRNAs could promote tumor development through ferroptosis., (© 2023. The Author(s).)

Objective: The aim of the present study was to evaluate the bioequivalence and safety of two types of daclatasvir hydrochloride tablets administered to healthy Chinese subjects under fasting and postprandial conditions., Materials and Methods: A total of 72 healthy Chinese subjects were randomly divided into two groups: the fasting group (n = 36) and the postprandial group (n = 36). A dose of 60 mg of both the test and reference preparations of the daclatasvir hydrochloride tablets was taken orally under fasting and postprandial conditions., Results: The main plasma pharmacokinetic parameters of the test and reference preparations in the fasting group were as follows: T 1/2 was 9.82 ± 1.00 and 9.67 ± 0.99 hours, respectively; t max was 1.00 hour in both; C max was 1,528.25 ± 428.80 and 1,504.25 ± 414.50 ng/mL -1 , respectively; AUC 0-t was 14,553.04 ± 4,013.26 and 14,391.97 ± 4,078.18 h/ng/mL -1 , respectively; the AUC 0-∞ was 14,660.80 ± 4,018.37 and 14,494.85 ± 4,095.57 ng/mL -1 , respectively. Meanwhile, the main plasma pharmacokinetic parameters of the test and reference preparations in the postprandial group were as follows: T 1/2 was 10.18 ± 1.38 and 10.18 ± 1.69 hours, respectively; t max was 2.00 and 1.75 hours, respectively; C max was 974.92 ± 248.50 and 981.44 ± 237.11 ng/mL -1 , respectively; AUC 0-t was 9,597.00 ± 3,094.28 and 9,982.83 ± 3,512.07 h/ng/mL -1 , respectively; AUC 0-∞ was 9,712.92 ± 3,130.43 and 10,113.97 ± 3,593.47 ng/mL -1 , respectively., Conclusion: Both types of daclatasvir hydrochloride tablets demonstrated good safety levels in healthy Chinese subjects under both fasting and postprandial conditions. Moreover, the two preparations were bioequivalent.

In this study, an inexact multistage stochastic mixed-integer programming (IMSMP) method was developed for supporting regional-scale energy system planning (EPS) associated with multiple uncertainties presented as discrete intervals, probability distributions and their combinations. An IMSMP-based energy system planning (IMSMP-ESP) model was formulated for Qingdao to demonstrate its applicability. Solutions which can provide optimal patterns of energy resources generation, conversion, transmission, allocation and facility capacity expansion schemes have been obtained. The results can help local decision makers generate cost-effective energy system management schemes and gain a comprehensive tradeoff between economic objectives and environmental requirements. Moreover, taking the CO 2 emissions scenarios mentioned in Part I into consideration, the anti-driving effect of carbon emissions on energy structure adjustment was studied based on the developed model and scenario analysis. Several suggestions can be concluded from the results: (a) to ensure the smooth realization of low-carbon and sustainable development, appropriate price control and fiscal subsidy on high-cost energy resources should be considered by the decision-makers; (b) compared with coal, natural gas utilization should be strongly encouraged in order to insure that Qingdao could reach the carbon discharges peak value in 2020; (c) to guarantee Qingdao's power supply security in the future, the construction of new power plants should be emphasised instead of enhancing the transmission capacity of grid infrastructure., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objectives: To assess the safety and tolerance of healthy volunteers to as tragalosides injection (AGI), and to determine a safe dose range for phase II clinical trial., Methods: A total of 62 healthy volunteers participated in this study, with 26 being given a single AGI of 100 mL, 200 mL, 300 mL, 400 mL, 500 mL, or 600 mL and 36 subjects being given 500 mL, 400 mL, 200 mL or 300 mL of AGI once a day for 7 d. Discomfortsymptoms, vital signs and safety problems were recorded 3 d and 7 d after the administration of AGI. The results were analyzed., Results: Of the 62 participants, 40 adverse events (AEs) were reported by 31 participants, which included 23 mild adverse reactions (ADRs) and 4 moderate ADRs. Nine AEs were reported by 9 participants with single AGI, including 7 ADRs. Fourteen AEs were reported by 10 participants with 500 mL and 400 mL multiple AGI, including 12 ADRs occurred in 9 participants.Seventeen AEs were reported by 12 participants with 300 mL and 300 mL multiple AGI, including 3 mild ADRs. The main ADRs included abnormal liver function [slightly elevated glutamic pyruvic transaminase (ALT), glutamic oxaloacetic transaminase (AST),and serum total bilirubin (TBil)], low blood potassium, increased urine red blood cell count, rash, and phlebitis., Conclusions: The maximum tolerance is 600 mL for single-dose treatment, and 400 mL for multiple-dose (7 d). The dose guidance given in this study should be examined its effects and safety in patients with coronary heart disease in phase II clinical trial.

As a gynecological oncology, ovarian cancer has high incidence and mortality. To study the mechanisms of ovarian cancer, the present study analyzed the GSE37582 microarray. GSE37582 was downloaded from Gene Expression Omnibus and included data from 74 ovarian cancer cases and 47 healthy controls. The differentially-expressed genes (DEGs) were screened using linear models for microarray data package in R and were further screened for functional annotation. Next, Gene Ontology and pathway enrichment analysis of the DEGs was conducted. The interaction associations of the proteins encoded by the DEGs were searched using the Search Tool for the Retrieval of Interacting Genes, and the protein-protein interaction (PPI) network was visualized by Cytoscape. Moreover, module analysis of the PPI network was performed using the BioNet analysis tool in R. A total of 284 DEGs were screened, consisting of 145 upregulated genes and 139 downregulated genes. In particular, downregulated FBJ murine osteosarcoma viral oncogene homolog (FOS) was an oncogene, while downregulated cyclin-dependent kinase inhibitor 1A (CDKN1A) was a tumor suppressor gene and upregulated cluster of differentiation 44 (CD44) was classed as an 'other' gene. The enriched functions included collagen catabolic process, stress-activated mitogen-activated protein kinases cascade and insulin receptor signaling pathway. Meanwhile, FOS (degree, 15), CD44 (degree, 9), B-cell CLL/lymphoma 2 (BCL2; degree, 7), CDKN1A (degree, 7) and matrix metallopeptidase 3 (MMP3; degree, 6) had higher connectivity degrees in the PPI network for the DEGs. These genes may be involved in ovarian cancer by interacting with other genes in the module of the PPI network (e.g., BCL2-FOS, BCL2-CDKN1A, FOS-CDKN1A, FOS-CD44, MMP3-MMP7 and MMP7-CD44). Overall, BCL2, FOS, CDKN1A, CD44, MMP3 and MMP7 may be correlated with ovarian cancer.

A new esterase gene abmbh, encoding a benzoate hydrolase which can enantioselectively hydrolyze l-menthyl benzoate to l-menthol, was recently identified from the genomic library of a soil isolate Acinetobacter sp. ECU2040. The abmbh gene contains a 1080-bp open reading frame encoding a protein of 360 amino acids with a calculated molecular mass of 40.7 kDa. The corresponding enzyme AbMBH was functionally expressed in Escherichia coli BL21 (DE3), purified, and characterized. The AbMBH displayed the maximum activity towards p-nitrophenyl butyrate at 50 °C, and an optimum pH of 8.5. A K M of 2.6 mM and a k cat of 0.26 s(-1) were observed towards dl-menthyl benzoate. The AbMBH exhibited a moderate enantioselectivity (E = 27.5) towards dl-menthyl benzoate. It can also catalyze the enantioselective hydrolysis of a variety of racemic menthyl esters, including dl-menthyl acetate, dl-menthyl chloroacetate, and dl-menthyl butyrate.

A series of chlorophyll a-based chlorins conjugated with pyridyl or quinoxalyl group at different positions were synthesized, characterized and evaluated for their photodynamic effect in vitro. It was found that all the pyridyl and quinoxalyl chlorins showed promising photocytotoxicities but nontoxic without irradiation in HeLa cells, and the substituted types and positions had a significant influence on the photocytotoxicities of the chlorophyll a-based chlorins. All the chlorins with a pyridyl group at the C-D ring end exhibited relatively high photocytotoxicity as compared to those with 3(2)-pyridyl. Among them, compound 12 conjugated with a pyridyl group at its C12 position showed the best photodynamic effect in HeLa cells with an IC50 value of 0.033μM. These facts, associated with the relative high long wavelength absorptions of those chlorins may provide valuable ways to design and prepare promising photosensitizers for application in photodynamic therapy., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Ethnopharmacological Relevance: Hydroxysafflor yellow A (HSYA), the major active marker compound isolated from Carthamus tinctorius L., has been demonstrated to possess various attractive pharmacological activities. However, there is a lack of information about the complete clinical pharmacokinetic profiles of HSYA following the administration of its pure preparations. The purpose of this study was to fully characterize the pharmacokinetic (PK) properties of HSYA in healthy Chinese volunteers following drip intravenous infusion of injectable powder of pure HSYA (IPPH), a new drug recently approved for the phase I clinical study by China Food and Drug Administration., Materials and Methods: 36 healthy subjects of either sex were recruited in this single-center, and open-label, single doses (25, 50, and 75 mg) and multiple doses (50 mg, once daily, 7 consecutive days) study. Plasma samples were analyzed with a validated LC-MS/MS method. Various PK parameters were estimated from the plasma concentration versus time data using non-compartmental methods., Results: After single dose administration of IPPH, the values of AUC(0-t), AUC(0-∞) and C(max) for HSYA were statistically proportional over the dose range of 25-75 mg. After 7 repeated doses of 50 mg IPPH, both C(max) and AUC(0-∞) were significantly decreased, from 3207 to 2959 μg L(-1), and from 12,811 to 12,135 µg h L(-1) respectively, while t(1/2) was significantly prolonged from 3.912 to 4.414 h. The minimum plasma concentrations on day 5, 6 and 7 showed good stability with no significant difference. Both Cmax and AUC of HSYA in male volunteers were generally lower than that in females. IPPH was generally well tolerated in healthy volunteers by either single or multiple dosing., Conclusion: HSYA displayed moderately linear PK properties over the doses ranging from 25 to 75 mg of IPPH. Repeated administration of IPPH once daily could not lead to the in-vivo drug accumulation, but significantly affect PK behavior of HSYA. Gender difference should be considered for dosage recommendation in the clinic., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Treatment of methyl mesopyropheophorbide a with formaldehyde under basic conditions gave a novel 13(2)-methylene derivative in 85% yield; under acidic conditions, the corresponding 20-hydroxymethyl derivative was obtained in 65% yield. The high reactivity of the enone structural motif existed in the former product provides a unique way to construct some novel chlorophyll a derivatives for various applications. Stereoselective Michael reaction of this compound is studied and discussed.