Micro-kinetic modelling of the CO reduction reaction on single atom catalysts accelerated by machine learning.

Electrochemical CO2 transformation to fuels and chemicals is an effective strategy for conversion of renewable electric energy into storable chemical energy in combination with reducing green-house gas emission. Metal-nitrogen-carbon (M-N-C) single atom catalysts (SAC) have shown great potential in the electrochemical CO2 reduction reaction (CO2RR). However, exploring advanced SACs with simultaneously high catalytic activity and high product selectivity remains a great challenge. In this study, density functional theory (DFT) calculations are combined with machine learning (ML) for rapid and high-throughput screening of high performance CO reduction catalysts. Firstly, the electrochemical properties of 99 M-N-C SACs were calculated by DFT and used as a database. By using different machine learning models with simple features, the investigated SACs were expanded from 99 to 297. Through several effective indicators of catalyst stability, inhibition of the hydrogen evolution reaction, and CO adsorption strength, 33 SACs were finally selected. The catalytic activity and selectivity of the remaining 33 SACs were explored by micro-kinetic simulation based on Marcus theory. Among all the studied SACs, Mn-NC2, Pt-NC2, and Au-NC2 deliver the best catalytic performance and can be used as potential catalysts for CO2/CO conversion to hydrocarbons with high energy density. This effective screening method using a machine learning algorithm can promote the exploration of CO2RR catalysts and significantly reduce the simulation cost.

Utility of intra-procedural cone-beam computed tomography imaging for the determination of the artery of Adamkiewicz suspected by angiography during transarterial embolization for hemoptysis.

PURPOSE: To evaluate the role of cone-beam computed tomography (CT) performed for the determination of the artery of Adamkiewicz (AKA) suspected by angiography during trans-catheter bronchial artery embolization for hemoptysis. METHODS: In this retrospective study, 17 patients with hemoptysis who underwent cone-beam CT for evaluation of the AKA prior to arterial embolization from December 2014 to March 2022 were included. During the angiographic session, two interventional radiologists selected the possible AKAs that were defined as obscured hairpin-curved vessels arising from the dorsal branch of the intercostal arteries and running towards the midline in the arterially enhanced phase. Contrast-enhanced cone-beam CT was performed as an adjunct to angiography to determine whether the indefinite AKA was a real AKA based on whether it was found to connect to the anterior spinal artery. RESULTS: Selective cone-beam CT was performed at 17 possible AKAs detected by selective arteriogram of the intercostal artery (ICA). Cone-beam CT allowed for the determination of AKAs in 16 cases (94.1%). As a result of cone-beam CT findings, 9 of 16 study arteries (56.3%) were judged as definite AKAs, and the remaining 7 (43.7%) were judged as definitely not AKAs but as the musculocutaneous branching from the dorsal branch of the ICA. In 1 of 17 cases (5.9%), cone-beam CT could not determine the AKA because of poor image quality caused by inadequate breath holding. An additional anterior radiculomedullary artery arising from the dorsal branch of the lower ICA because of the inflow of the contrast medium through the anastomosis was detected in one case by conebeam CT but not by angiography. CONCLUSION: Intraprocedural enhanced cone-beam CT performed as an adjunctive technique to angiography is sufficient for confident determination of the AKA, which is essential for the operators to perform accurate and safe arterial embolization for hemoptysis.

Chiral nanocrystals grown from MoS2 nanosheets enable photothermally modulated enantioselective release of antimicrobial drugs.

The transfer of the concept of chirality from molecules to synthesized nanomaterials has attracted attention amongst multidisciplinary teams. Here we demonstrate heterogeneous nucleation and anisotropic accumulation of Au nanoparticles on multilayer MoS2 planes to form chiroptically functional nanomaterials. Thiol amino acids with chiral conformations modulate asymmetric growth of gold nanoarchitectures on seeds of highly faceted Au/MoS2 heterostructures. Consequently, dendritic plasmonic nanocrystals with partial chiral morphologies are synthesized. The chirality of dendritic nanocrystals inherited from cysteine molecules refers to the structural characteristics and includes specific recognition of enantiomeric molecules. With integration of the intrinsic photothermal properties and inherited enantioselective characteristics, dendritic Au/MoS2 heterostructures exhibit chirality-dependent release of antimicrobial drugs from hydrogel substrates when activated by exogenous infrared irradiation. A three-in-one strategy involving synthesis of chiral dendritic heterostructures, enantioselective recognition, and controlled drug release system is presented, which improves nanomaterial synthetic technology and enhances our understanding of crucial chirality information.

Analysis of the network pharmacology and the structure-activity relationship of glycyrrhizic acid and glycyrrhetinic acid.

Licorice, a herbal product derived from the root of Glycyrrhiza species, has been used as a sweetening agent and traditional herbal medicine for hundreds of years. Glycyrrhizic acid (GL) and glycyrrhetinic acid (GA) are the most important active ingredients in licorice. Both GL and GA have pharmacological effects against tumors, inflammation, viral infection, liver diseases, neurological diseases, and metabolic diseases. However, they also exhibit differences. KEGG analysis indicated that licorice is involved in neuroactive ligand‒receptor interactions, while 18ß-GA is mostly involved in arrhythmogenic right ventricular cardiomyopathy. In this article, we comprehensively review the therapeutic potential of GL and GA by focusing on their pharmacological effects and working mechanisms. We systemically examine the structure-activity relationship of GL, GA and their isomers. Based on the various pharmacological activities of GL, GA and their isomers, we propose further development of structural derivatives of GA after chemical structure modification, with less cytotoxicity but higher targeting specificity. More research is needed on the clinical applications of licorice and its active ingredients.

HBV triggers APOBEC2 expression through miR­122 regulation and affects the proliferation of liver cancer cells.

Hepatitis B virus (HBV) infection is responsible for 50% of liver cancer cases globally; this disease is one of the leading causes of cancer­associated mortality. One reported mechanism underlying the development of liver cancer is the mutation of tumor suppressor genes induced by the overexpression of apolipoprotein B mRNA­editing enzyme catalytic subunit 2 (APOBEC2) in hepatocytes. In addition, it has been observed that HBV inhibited microRNA (miR)­122 expression in hepatocytes; however, the molecular mechanisms involved in liver cancer development remain unknown and further investigations are required. In the present study, the mechanistic roles of HBV infection in modulating the expression of miR­122 and APOBEC2, and the development of liver cancer, were investigated. Reverse transcription­quantitative PCR and western blot analyses revealed that APOBEC2 expression was markedly upregulated following HBV infection. Of note, the expression profile of APOBEC2 in the Huh7 and HepG2 liver cancer cell lines opposed that of miR­122; this miR is the most abundant miRNA in the liver and has been associated with hepatocarcinogenesis. Mechanistically, it was demonstrated via a dual­luciferase assay that miR­122 could specifically bind to the 3'­untranslated region (3'UTR) of APOBEC2 mRNA, inhibiting its expression. Collectively, the findings of the present study may provide insight into the mechanistic role of HBV infection in modulating the expression of miR­122, which targets the 3'UTR of APOBEC2 mRNA, subsequently inducing liver carcinogenesis.

Pneumonic plague epidemic in Northeast China in 1910-1911: Dr. Wu Lien-Teh's epidemic preventive system for plague control.

Pneumonic plague that originated in Russian Siberia broke out in Northeast China in October 1910-March 1911. On the basis of field visits, autopsy, bacteriological identification, and close collaboration with local authorities and international colleagues, Dr. Wu Lien-Teh implemented a series of efficient antiplague measures, which successfully controlled the development of an extraordinary epidemic plague. In his subsequent work, Dr. Wu demonstrated the respiratory transmission of pneumonic plague and tarbagans' role in this spread. Dr.Wu's academic and cultural contributions are valuable in the medical progress in China.

Solid-state pulse forming module with adjustable pulse duration.

A new solid-state pulse forming module is described in this paper. The pulse forming module is fabricated on a glass ceramic substrate, with the dimension of 250 mm × 95 mm × 4 mm. By changing the copper strips used in the pulse forming modules, the pulse duration of the obtained pulsed can range from 80 ns to 140 ns. Both the simulation and tests show that the pulse forming module has a good pulse forming ability. Under a high voltage in microsecond's time, the new pulse forming modules can hold off a voltage up to 25 kV higher than that of the previous study. In addition, future optimization for the field enhancement near the thin electrode edge has been proposed and simulated.

[Imaging features of hip joint in patients with ankylosing spondylitis undergoing total hip arthroplasty].

Objective: To study the imaging features of the hip joint by measuring the imaging parameters of spine, pelvis, and hip joint before and after total hip arthroplasty (THA) in patients with ankylosing spondylitis (AS) undergoing THA so as to provide reference for selection of operation methods and prosthesis. Methods: Between January and July 2015, 38 patients (56 hips) with AS underwent primary THA as AS group, and 36 patients (45 hips) with osteonecrosis of the femoral head underwent THA as control group. There was no significant difference in side ( χ2=1.14, P=0.95). The acetabular abduction angle (ABA), acetabular anteversion angle (AVA), center collum diaphyseal (CCD), offset, height from rotation center to lesser trochanter (HRCLT), femoral intertrochanteric distance (FID) were measured by CT three-dimensional morphology. The canal flare index (CFI), cortical thickness index (CTI), pelvic incidence (PI), sacral slope (SS), and pelvic tilt (PT) were measured by X-ray film before operation. The AVA, ABA, and the filling ratio were measured on the postoperative X-ray film. Results: There was no significant difference in preoperative AVA and ABA and postoperative ABA between 2 groups ( P>0.05), but significant difference was found in postoperative AVA ( t=6.71, P=0.00). The mean PI, SS, and PT in AS group were 48.37° (range, 41-58°), 5.64°(range, 2-11°), and 12.85° (range, 5-26°), respectively. There was significant difference in CCD, CFI, and CTI between 2 groups ( t=3.63, P=0.04; t=5.12, P=0.02; t=3.91, P=0.04), but offset, HRCLT, and FID all showed no significant difference ( t=0.41, P=0.36; t=0.33, P=0.56; t=0.59, P=0.12). On the basis of the Noble classification, medullary cavity of the femur was rated as chimney type, ordinary type, and champagne flute type in 32, 18, and 6 hips of AS group, and in 4, 28, and 13 hips of control group respectively. Filling ratio of distal segment in AS group was significantly lower than that in control group ( t=5.64, P=0.02), but there was no significant difference in the filling ratio of middle and proximal segments between 2 groups ( t=0.29, P=0.61; t=0.55, P=0.13). Conclusion: Compared with patients having osteonecrosis of the femeral head, there is no significant difference in preoperative AVA and ABA, but postoperative AVA significantly increase in patients with AS. Because AS patients have mainly chimney type medullary cavity of the femur, the filling ratio of middle and distal segment is lower when tapered stems are used, and the filling ratio of anatomic stems is higher.

Two-stage revisions for culture-negative infected total knee arthroplasties: A five-year outcome in comparison with one-stage and two-stage revisions for culture-positive cases.

BACKGROUND: Culture-negative periprosthetic joint infection (PJI) is very intractable when dealing with an infected total knee arthroplasty (TKA) patient. Two-stage revision has been proved to be a reliable solution for PJI patients. Whether it is still credible for culture-negative infected patients remains uncertain. METHODS: Our group retrospectively reviewed all total knee revision patients from January 2003 to January 2014, 145 PJI patients were diagnosed as infection with the PJI diagnostic criteria and 129 patients were successfully followed. As different treating strategies were utilized, these patients were divided into culture-negative (18 cases, CN) group, culture-positive with one-stage revision group (CP1, 21 cases) and culture-positive with two-stage revision group (CP2, 87 cases) groups. The CN group and CP2 group underwent two-stage revision with antibiotic loaded cement spacers and intravenous antibiotics, CP1 group received one-stage revision. All the culture results and relevant medical records were thoroughly reviewed. RESULTS: The mean follow-up time was 59.5 ± 32.3 months (range 12-158 months). The culture-negative rate was 14.2%. The overall infection control rate was 92.12%. Infection recurrence was observed in two cases in CP1 group (9.09%), six cases in CP2 group (6.90%) and two cases in CN group (11.1%). The reinfection rate of culture-negative patients and culture-positive patients was 7.34% and 11.1% with no significant difference (p = 0.94). No statistically difference was observed between CP2 group and CN group (p = 0.90). No Spacer fracture or dislocation was observed. CONCLUSION: With combined or broad spectrum antibiotics, two-stage revision showed comparable outcome when treating culture-negative infected TKA patients at five-year follow-up.

Chlorpromazine inhibits mitochondrial apoptotic pathway via increasing expression of tissue factor.

Chlorpromazine (CPZ) is a widely used antipsychotic drug with antagonistic effect on dopamine receptors. Accumulating evidence has shown that CPZ plays a neuroprotective role in various models of toxicity and apoptosis. However, the underlying mechanism contributing to this protective effect remains unclear. Here, we evaluate the effect of CPZ on mitochondrial apoptotic pathway in the neuron system. Higher levels of B-cell lymphoma-2 (Bcl-2) and tissue factor (TF) but lower apoptotic rate were found in hippocampus of CPZ-treated schizophrenic patients compared with non-antipsychotic treated controls. Additionally, both short-term and long-term treatment of CPZ in rats could up-regulate the levels of Bcl-2 and TF with no cytotoxic effects. In the in vitro experiment, expression of Bcl-2 was up-regulated in the C6 glioma cells transfected with pEGFP-N1-TF recombinant plasmid. Furthermore, in another independent rat model of apoptosis, compared with the group administrated with alcohol only, the brains of the CPZ-pretreated rats showed lower expression of cleaved caspase-3, cytochrome c and Bax, but higher expression of Bcl-2 and TF. Our data demonstrate that CPZ exerts its neuronal protective effects through inhibiting the activation of mitochondrial apoptotic pathway by up-regulating TF expression, thus providing new insight into CPZ function and application.

[COMPARISON OF CEMENTLESS TOTAL HIP ARTHROPLASTY BETWEEN WITH AND WITHOUT SUBTROCHANTERIC FEMORAL SHORTENING OSTEOTOMY IN Crowe TYPE IV DEVELOPMENTAL DYSPLASIA OF HIP].

OBJECTIVE: To investigate the clinical characteristic differences of cementless total hip arthroplasty (THA) between with and without subtrochanteric femoral shortening osteostomy in Crowe type IV developmental dysplasia of the hip (DDH). METHODS: Between January 2006 and March 2012, 21 patients (21 hips) with Crowe type IV DDH who underwent primary THA were enrolled according to inclusion criteria. According to whether subtrochanteric femoral shortening osteostomy was performed during THA or not, the patients were divided into 2 groups: THA with osteostomy group (n = 9) and THA without osteotomy group (n = 12). There was no significant difference in gender, age, body mass index, and hip Harris score between 2 groups (P > 0.05) except leg length discrepancy (t = -3.170, P = 0.005). The operation time, blood loss, postoperative drainage, complications, and radiography data were compared to evaluate the clinical characteristics. RESULTS: The operation time, blood loss, and postoperative drainage of osteotomy group were all significantly greater than those of no osteotomy group (P < 0.05). All patients achieved primary healing of incision; 1 patient (1 hip) had transient sciatic nerve symptom in osteotomy group. The average follow-up time was 53 months (range, 28-88 months). The X-ray films showed good fracture healing at 3-6 months after operation in osteostomy group. No prosthetic loosening or dislocation was found. The hip Harris score was 90.67 ± 4.06 in osteostomy group and 92.17 ± 3.27 in no osteostomy group, showing no significant difference between 2 groups (t = -0.938, P = 0.360). The leg length discrepancy was (0.22 ± 0.26) cm in osteostomy group and (0.18 ± 0.27) cm in no osteostomy group, showing no significant.difference (t = 107.000, P = 0.546). The leg length discrepancy was found in 6 patients of osteotomy group and 5 patients of no osteotomy group. One patient complained of thigh pain in osteotomy group; 2 patients had slight limp (Trendelenburg +) in no osteotomy group. CONCLUSION: THA can improve joint function and increase limb length in the treatment of Crowe type IV DDH. Subtrochanteric shortening osteotomy is an effective treatment which can be performed according to preoperative template measurement, leg length shortening, and the soft tissue tension.

Development of a multiplex PCR system and its application in detection of blaSHV, blaTEM, blaCTX-M-1, blaCTX-M-9 and blaOXA-1 group genes in clinical Klebsiella pneumoniae and Escherichia coli strains.

Resistance to ß-lactam antibiotics through ß-lactamase production by Enterobacteriaceae continues to burden the health-care sector worldwide. Traditional methods for detection of ß-lactamases are time-consuming and labor-intensive and newer methods with varying capabilities continue to be developed. The objective of this study was to develop a multiplex PCR (M-PCR) system for the detection of blaSHV, blaTEM, blaCTX-M-1, blaCTX-M-9 and blaOXA-1 group genes and to apply it in clinical Klebsiella pneumoniae and Escherichia coli strains. To do this, we used group-specific PCR primers in singleplex reactions followed by optimization into multiplex reactions. Specificity and sensitivity of the M-PCR were then evaluated using 58 reference strains before its application to detect bla group genes in 203 clinical Enterobacteriaceae strains. PCR amplicons were sequenced to determine the ß-lactamase subtypes. The M-PCR system exhibited 100% specificity and sensitivity. In all, 83.7% of K. pneumoniae and 89.8% of E. coli clinical strains harbored bla group genes with 46.9%, 40.1%, 15.0%, 21.1% and 6.1% of K. pneumoniae having blaSHV, blaTEM, blaCTX-M-1, blaCTX-M-9 and blaOXA-1 group genes, respectively, whereas 12.2%, 77.6%, 22.4%, 36.7% and 8.2% of E. coli had blaSHV, blaTEM, blaCTX-M-1, blaCTX-M-9 and blaOXA-1 group genes, respectively. BlaSHV-1, blaSHV-11, blaSHV-27, blaSHV-33, blaSHV-144, blaTEM-1, blaTEM-135, blaOXA-1, blaCTX-M-3, blaCTX-M-9, blaCTX-M-14, blaCTX-M-15, blaCTX-M-27, blaCTX-M-55, blaCTX-M-65 and blaCTX-M-104 were detected. In conclusion, the M-PCR system was efficient and versatile with an advantage of simultaneously detecting all the targeted bla group genes. Hence, it is a potential candidate for developing M-PCR kits for the screening of these genes for clinical or epidemiological purposes.

[Application of modular cementless femoral stems in complex revision hip arthroplasty].

OBJECTIVE: To investigate and clarify the key surgical techniques and evaluate clinical effectiveness of modular cementless femoral stems(LINK MP modular stem) in complex revision hip arthroplasty. METHODS: From January 2002 to December 2013, 470 patients in Chinese PLA General Hospital received revision hip arthroplasties using MP stems. Among them, 246 patients were followed for an average of 5.7 years (ranged, 0.5 to 11 years). There were 148 males and 98 females, with an average age of 62.5 years old (ranged from 26 to 83 years old). The most common reason for revision was aseptic loosening of femoral stems (107 cases, 43.5%), followed by prosthetic joint infection (104 cases, 42.3%). Other reasons included unexplained hip or thigh pain, periprosthetic femoral fracture, prosthesis wear and dislocation. According to Paprosky classification of femoral deficiency, there were 171 cases of type IIIA (69.5%), 14 cases of type I, 39 cases of type II, and 22 cases of type IIIB. The average preoperative Harris hip score (HHS) was 37.4 ± 7.5. In addition, radiographic presentation, degree of patients' subjective satisfaction, and clinical effectiveness were assessed as well. RESULTS: The average Harris score was im- proved to 87.8 ± 4.2 after operation,with significant statistical difference when compared to preoperative score (t = 92.13,P = 0.00). Analysis of patients' subjective satisfaction for leg length discrepancy, stability and overall degree of satisfaction showed that the number of patients with great satisfaction were 27, 60, 61 respectively. The most common complication was the periprosthetic fracture (intraoperatively 21 cases and postoperatively 8 cases). Other complications included infection (7 cases), dislocation (5 cases), numbness possibly caused by incomplete sciatic nerve injury (6 cases) and thigh swelling (3 cases). The X-ray taken at the final follow-up revealed that prosthesis subsidence occurred in 4 cases, 2 of which needed a second revision. CONCLUSION: The application of modular cementless femoral stems (LINK MP modular stem) in complex revision hip arthroplasty (especially in cases with the serious defect of proximal femoral bone) shows good results at both the short-term and long-term follow-up, especially in the revision for prosthetic infection with the high success rate. In order to avoid complications and improve clinical outcomes,the surgeons should carefully select proper surgery candidates,perform the procedure with care, and master the key surgical techniques.

Serum metabolites as potential biomarkers for diagnosis of knee osteoarthritis.

Knee osteoarthritis (OA) is a highly prevalent chronic degenerative joint disease that mainly affects the elderly population. The aim of this study was to investigate serum signature metabolites as potential biomarkers for early diagnosis of knee OA. Global serum metabolic profiles of 40 patients with knee OA and 20 healthy controls (HC) were analyzed by ultra-performance liquid chromatography coupled to mass spectrometry. An OA-specific metabolic profile was established that can clearly discriminate patients with OA from HCs. Fourteen metabolites that are involved in the metabolism of amino acids, purine, energy, glycolysis, fatty acids, and lipids were significantly altered in patients with OA compared to HCs. These metabolites could be potentially used as biomarkers for the diagnosis of knee OA.

Down-regulation of suppressor of cytokine signaling 3 by miR-122 enhances interferon-mediated suppression of hepatitis B virus.

MicroRNA-122 (miR-122) is involved in the pathogenesis of several liver diseases, including chronic hepatitis B infection and hepatocellular carcinoma. This study aimed to explore the potential role of miR-122 in the interferon (IFN)-mediated suppression of hepatitis B virus (HBV) in hepatocytes. We found that elevated expression of suppressor of cytokine signaling 3 (SOCS3) following HBV infection, contributed to the inactivation of the IFN signaling pathway. Based on previous studies from our laboratory showing that miR-122 can modulate type I IFN expression by inhibiting SOCS1 expression, we analyzed the SOCS3 mRNA sequence for putative miR-122 binding sites. We demonstrate that miR-122 inhibits SOCS3 expression by targeting the 3'-untranslated region of the SOCS3 mRNA within the region 1887-1910 nucleotides. Finally, we demonstrate that significantly increased levels of IFN lead to decreased HBV expression in miR-122 mimic-treated Huh7 cells, whereas inhibition of endogenous miR-122 leads to enhanced viral production, owing to a marked decrease in IFN expression. Taken together, our results demonstrate that miR-122 down-regulates SOCS3, thus positively affecting the anti-HBV efficiency of endogenous type I IFN. Our study suggests that suppression of miR-122 induced by HBV infection, leads to the inactivation of IFN expression, which in turn enhances HBV replication, contributing to viral persistence and hepatocarcinogenesis.

No evidence of superiority in reducing outliers of component alignment for patient-specific instrumentation for total knee arthroplasty: a systematic review.

Patient-specific instrumentation (PSI) technology has been developed to improve alignment when implanting total knee arthroplasty (TKA) and is a new focus in the orthopaedic community. Current controversial data concerning PSI are discussed. A systematic review to compare PSI with conventional instrumentation and assess the radiographic outcomes was performed. Electronic databases (including PubMed, Medline, Embase, the Cochrane Library and the Science Citation Index database) and conference proceedings from 1950 to 2014 in the English language were searched. Data, including relevant patient characteristics, sample size, radiographic method, PSI system manufacturer and outliers of implant positioning and alignment on radiography were independently extracted from all eligible studies by two of the authors. A total of 2739 TKAs were included (1410 performed with PSI and 1329 with conventional instrumentation). There were more TCA outliers (malalignment >3°) and tibial slope outliers (malalignment >3°) in the PSI group than in the conventional group. The other radiographic outcomes assessed, including coronal, sagittal or rotational alignment outliers did not differ between the two groups. With regard to radiographic outcomes, our findings indicate that PSI technology is not superior in reducing outliers of component alignment.

[COMPARISON OF PERIOPERATIVE INFLAMMATORY MARKERS BETWEEN PATIENTS WITH ANKYLOSING SPONDYLITIS AND NON-INFLAMMATORY DISEASES UNDERGOING TOTAL HIP ARTHROPLASTY].

OBJECTIVE: To evaluate the inflammatory markers in patients with ankylosing spondylitis (AS) or non-inflammatory diseases undergoing total hip arthroplasty (THA) and to ascertain the variation trend of perioperative inflammatory markers and the influence of inflammation markers after THA. METHODS: Between January 2013 and December 2014, 153 consecutive patients with AS were included. According to the range of motion (ROM), the patients were divided into ankylosis group (ROM: 0 degrees; group A, n = 92) and stiff group (ROM: 3-46 degrees; group B, n = 61); 120 non-inflammatory diseases patients having no bacterial infection and undergoing primary THA served as non-inflammatory group (group C). The inflammatory markers including C-reactive protein (CRP), interleukin-6 (IL-6), and erythrocyte sedimentation rate (ESR) concentrations were measured before operation and at 1, 3, 5, and 7 days after operation, and the complication was observed. RESULTS: Perioperative serum CRP, IL-6, and ESR increased at first after operation, and then decreased in 3 groups. There were significant differences in CRP and ESR between at pre- and post-operation (P < 0.05); the IL-6 at 1, 3, and 5 days after operation were significantly higher than that at preoperation (P<0.05), but no significant difference was found between at 7 days and at preoperation (P > 0.05). CRP, IL-6, and ESR of group B were significantly higher than those of group A at preoperation (P < 0.05); CRP and IL-6 of groups A and B were significantly higher than those of group C at preoperation and at 1 day after operation (P < 0.05); ESR of groups A and B was significantly higher than that of group C at preoperation, and at 1 day and 3 days after operation (P < 0.05); and no significant difference was shown among 3 groups at the other time points (P > 0.05). No inflammatory activity or increased complication was observed. CONCLUSION: AS and non-inflammatory diseases show similar change trend of inflammatory markers at pre- and post-operation. The inflammatory activity of AS has no significant effect on the changes of inflammation markers and does not increase the incidence of postoperative complications.

MiR-122 directly inhibits human papillomavirus E6 gene and enhances interferon signaling through blocking suppressor of cytokine signaling 1 in SiHa cells.

Human Papillomavirus (HPV) 16 infection is considered as one of the significant causes of human cervical cancer. The expression of the viral oncogenes like E6 and E7 play an important role in the development of the cancer. MiR-122 has been reported to exhibit a strong relationship with hepatitis viruses and take part in several tumor development, while the effects of miR-122 on HPV infection and the HPV viral oncogenes expression still remain unexplored. In this study, using RNAhybrid software, the potential binding sites between miR-122 and HPV16 E6 and E7 mRNAs were identified. Over and loss of miR-122 function showed that miR-122 could directly bind with HPV16 E6 mRNA and significantly inhibit its expression in SiHa cells, which was further confirmed by constructing the miR-122-E6-mu to eliminate the miR-122 binding effects with E6. The increase of the expression of type I interferon (IFN) and its classical effective molecules and the phosphorylation of signal transducers and activators of transcription (STAT1) protein indicated that miR-122 might enhance type I interferon in cervical carcinoma cells, which explained the significant reduction of HPV16 E7 and E6*I mRNA expression. This might be due to the binding between miR-122 and suppressor of cytokine signaling 1 (SOCS1) mRNA, which is the suppressor of interferon signaling pathway. Moreover, it was identified that the miR-122 binding position was nt359-nt375 in SOCS1 mRNA. Taken together, this study indicated that HPV16 could be effectively inhibited by miR-122 through both direct binding with E6 mRNA and promoting SOCS1-dependent IFN signaling pathway. Thus, miR-122 may serve as a new therapeutic option for inhibiting HPV infection.

Interleukin-12 gene adjuvant increases the immunogenicity of virus-like particles of human papillomavirus type 16 regional variant strain

Objectives: To analyze the immunogenicity of virus-like particles (VLP) of human papillomavirus type 16 (HPV16) isolated in East China and the adjuvant potential of interleukin-12 (IL-12). Methods: The variant HPV16 L1VLP expressed in sf9 insect cells were purified with cesium chloride gradient centrifugation. BALB/c mice were vaccinated with VLP (L1N), VLP with Freund's adjuvant (L1A) or VLP with IL-12 recombinant plasmid (L1P). HPV16 VLP specific IgG and IFN-γ level in the serum were detected by ELISA, and the percentage of CD4+ and CD8+ in spleen cells was detected with flow cytometry. Results: The titers of serum IgG antibodies in vaccinated groups were higher than in negative control and the serum antibodies mainly recognized conformation-dependent HPV16 VLP epitopes. Splenic CD4+ and CD8+ T cell subsets increased after vaccination in every experimental group, and CD8+ increased obviously in L1P group. The ratio of CD4+/CD8+ decreased in L1P group and increased in the other two groups, compared to control group. Vaccination induced specific secretion of IFN-γ in the serum of vaccinated group (p < 0.05), especially in the L1P group. Conclusions: VLP of HPV16 variant strain isolated in East China could induce humoral immunity and cellular immunity in mice, and IL-12 recombinant plasmid can enhance cellular immunity. .