Prevalence and genotype distribution of human papillomavirus infection among 66000 women from 2014 to 2023 in the plateau region of Southwest China.

BACKGROUND: Persistent infection with high-risk human papillomavirus (HR-HPV) plays a key role in the onset of cervical cancer. This study was designed to examine the epidemiological trends and genotype distribution of HPV from 2014 to 2023 in the plateau region of Southwest China. METHODS: The findings could offer valuable insights for clinical screening of cervical cancer and the formulation of HPV vaccination policies. This retrospective study analyzed 66,000 women who received HPV-DNA testing at the First People's Hospital of Qujing, Yunnan, China, between 2014 and 2023. The cohort consisted of 33,512 outpatients, 3,816 inpatients, and 28,672 individuals undergoing health examinations. Cervical cells were collected for DNA extraction, and PCR amplification along with Luminex xMAP technology were used to detect 27 HPV genotypes. The data analysis was conducted using GraphPad Prism and IBM SPSS Statistics 27 software. RESULTS: The overall HPV infection rate at the First People's Hospital of Qujing declined from 24.92% in 2014 to 16.29% in 2023, averaging 16.02%. Specific infection rates were 18.50% among outpatients, 12.97% among inpatients, and 13.53% for health examination attendees. The predominant high-risk HPV genotypes identified were HPV52 (2.61%), HPV16 (2.06%), HPV58 (1.81%), HPV53 (1.55%), and HPV39 (1.09%). Meanwhile, the most frequent low-risk HPV genotypes were HPV6 (1.30%), HPV61 (1.21%), and HPV11 (0.85%). In HPV-positive cases, the distribution of single, double, triple, and quadruple or more infections were 79.90%, 15.17%, 3.59%, and 1.33%, respectively. The proportions of pure LR-HPV, pure HR-HPV, and mixed infections were 22.16%, 67.82%, and 10.02%, respectively. Age-specific analysis revealed a bimodal distribution of HPV infection, with the infection rate rapidly decreasing from 44.02% in the ≤ 19 age group to 19.55% in the 20-29 age group and 13.84% in the 30-39 age group, followed by a gradual increase to 14.64% in the 40-49 age group, 16.65% in the 50-59 age group, and 22.98% in the ≥ 60 age group. The coverage rates of the three available vaccines are all below 50%. The results of this study indicated a declining trend in HPV prevalence in the plateau region of Southwest China over the period from 2014 to 2023, especially in the reduction of genotypes targeted by vaccines. CONCLUSION: There were significant variations in the genotypes prevalent among different age groups, years, and patient sources within the same region. The underwhelming vaccination rates emphasize the critical need for developing either a multivalent vaccine or a personalized vaccine that targets the HPV genotypes common in the Chinese population. Furthermore, vaccinating adolescents to curb HPV infection and ensuring regular cervical cancer screenings for postmenopausal women are crucial steps.

Synergistic Effects of TiO2 and Carbon Black for Water Evaporation-Induced Electricity Generation.

Water evaporation-induced electricity generators (WEGs) have drawn widespread attention in the field of hydrovoltaic technology, which can convert atmospheric thermal energy into sustainable electric power. However, it is restricted in the wide application of WEGs due to the low power output, complex fabrication process, and high cost. Herein, we present a simple and effective approach to fabricate TiO2-carbon black film-based WEGs (TC-WEGs). A single TC-WEG device can sustainably output an open-circuit voltage of 1.9 V and a maximum power density of 40.9 µW/cm2. Moreover, it has been shown that TC-WEGs exhibit stable electrical energy output when operating in seawater, which can yield a short-circuit current of 1.2 µA. The superior electricity generation performance can be attributed to the intrinsic characteristics of the TC-WEGs, including hydrophilicity, porous structure, and electrical conductivity. This work provides an important reference for the constant harvesting of clean energy.

Revealing the role of interfacial water and key intermediates at ruthenium surfaces in the alkaline hydrogen evolution reaction.

Ruthenium exhibits comparable or even better alkaline hydrogen evolution reaction activity than platinum, however, the mechanistic aspects are yet to be settled, which are elucidated by combining in situ Raman spectroscopy and theoretical calculations herein. We simultaneously capture dynamic spectral evidence of Ru surfaces, interfacial water, *H and *OH intermediates. Ru surfaces exist in different valence states in the reaction potential range, dissociating interfacial water differently and generating two distinct *H, resulting in different activities. The local cation tuning effect of hydrated Na+ ion water and the large work function of high-valence Ru(n+) surfaces promote interfacial water dissociation. Moreover, compared to low-valence Ru(0) surfaces, high-valence Ru(n+) surfaces have more moderate adsorption energies for interfacial water, *H, and *OH. They, therefore, facilitate the activity. Our findings demonstrate the regulation of valence state on interfacial water, intermediates, and finally the catalytic activity, which provide guidelines for the rational design of high-efficiency catalysts.

Gastrodia elata and parishin ameliorate aging induced 'leaky gut' in mice: Correlation with gut microbiota.

BACKGROUND: The aging-induced decrease in intestinal barrier function contributes to many age-related diseases. Studies on preventive measures for "leaky gut" may help improve the quality of life of geriatric patients. The potent anti-aging effect of Gastrodia elata and parishin, which is one of its active ingredients, has been reported previously. However, their effects on the gut remain elusive, and the effect of parishin on mammals has not been studied. METHODS: We used quantitative RT-PCR, western blotting, immunohistochemical analysis, and 16S rRNA sequencing to investigate the effect of G. elata and parishin on the intestinal barrier function of D-Gal-induced aging mice. RESULTS: G. elata and parishin prevented the decrease in tight junction protein (TJP) expression and morphological changes, modulated the composition of fecal microbiota to a healthier state, and reversed the translocation of microbial toxins and systemic inflammation. The correlation analyses showed that TJP expression and systemic inflammation were significantly positively or negatively correlated with the composition of fecal microbiota after G. elata and parishin administration. Additionally, TJP expression was also correlated with systemic inflammation. Moreover, G. elata and parishin administration reversed the decreased or increased expression of aging-related biomarkers, such as FOXO3a, SIRT1, CASPASE3 and P21, in the gut. CONCLUSIONS: These results suggested that G. elata and parishin could prevent gut aging and ameliorate the "leaky gut" of aged mice and that the underlying mechanism is related to the mutual correlations among barrier function, fecal microbiota composition, and inflammation.

Concurrent definitive chemoradiation incorporating intensity-modulated radiotherapy followed by adjuvant chemotherapy in high risk locally advanced cervical squamous cancer: a phase II study.

BACKGROUND: Although the prognosis of locally advanced cervical cancer has improved dramatically, survival for those with stage IIIB-IVA disease or lymph nodes metastasis remains poor. It is believed that the incorporation of intensity-modulated radiotherapy into the treatment of cervical cancer might yield an improved loco-regional control, whereas more cycles of more potent chemotherapy after the completion of concurrent chemotherapy was associated with a diminished distant metastasis. We therefore initiated a non-randomized prospective phaseII study to evaluate the feasibility of incorporating both these two treatment modality into the treatment of high risk locally advanced cervical cancer. OBJECTIVES: To determine whether the incorporation of intensity-modulated radiotherapy and the addition of adjuvant paclitaxel plus cisplatin regimen into the treatment policy for patients with high risk locally advanced cervical cancer might improve their oncologic outcomes. STUDY DESIGN: Patients were enrolled if they had biopsy proven stage IIIA-IVA squamous cervical cancer or stage IIB disease with metastatic regional nodes. Intensity-modulated radiotherapy was delivered with dynamic multi-leaf collimators using 6MV photon beams. Prescription for PTV ranged from 45.0 ~ 50.0 Gy at 1.8 Gy ~ 2.0 Gy/fraction in 25 fractions. Enlarged nodes were contoured separately and PTV-nodes were boosted simultaneously to a total dose of 50.0-65 Gy at 2.0- 2.6 Gy/fraction in 25 fractions. A total dose of 28 ~ 35 Gy high-dose- rate brachytherapy was prescribed to point A in 4 ~ 5 weekly fractions using an iridium- 192 source. Concurrent weekly intravenous cisplatin at 30 mg/m2 was initiated on the first day of radiotherapy for over 1-h during external-beam radiotherapy. Adjuvant chemotherapy was scheduled within 4 weeks after the completion of concurrent chemo-radiotherapy and repeated 3 weeks later. Paclitaxel 150 mg/m2 was given as a 3-h infusion on day1, followed by cisplatin 35 mg/m2 with 1-h infusion on day1-2 (70 mg/m2 in total). RESULTS: Fifty patients achieved complete response 4 weeks after the completion of the treatment protocol, whereas 2 patients had persistent disease. After a median follow-up period of 66 months, loco-regional (including 2 persistent disease), distant, and synchronous treatment failure occurred in 4,5, and 1, respectively. The 5-year disease-free survival, loco-regional recurrence-free survival, distant-metastasis recurrence-free survival was 80.5%, 90.3%, and 88.0%, respectively. Four of the patients died of the disease, and the 5-year overall survival was 92.1%. Most of the toxicities reported during concurrent chemo-radiotherapy were mild and transient. The occurrence of hematological toxicities elevated mildly during adjuvant chemotherapy, as 32% (16/50) and 4% (2/50) patients experienced grade 3-4 leukopenia and thrombocytopenia, respectively. Grade 3-4 late toxicities were reported in 3 patients. CONCLUSIONS: The incorporation of intensity-modulated radiotherapy and adjuvant paclitaxel plus cisplatin chemotherapy were highly effective and well-tolerated in the treatment of high-risk locally advanced cervical cancer. The former yields an improved loco-regional control, whereas distant metastases could be effectively eradicated with mild toxicities when adjuvant regimen was prescribed.

Three-dimensional electroanatomical mapping guidelines for the selection of pacing site to achieve cardiac resynchronization therapy.

Objectives: We aimed to evaluate the feasibility of left ventricular electroanatomical mapping to choose between left bundle branch area pacing (LBBAP) or coronary venous pacing (CVP). Background: There are several ways to achieve left ventricular activation in cardiac resynchronization therapy (CRT): LBBAP and CVP are two possible methods of delivering CRT. However, the criteria for choosing the best approach remains unknown. Methods: A total of 71 patients with heart failure, reduced ejection fraction, and left bundle branch block (LBBB) were recruited, of which 38 patients underwent the three-dimensional electroanatomical mapping of the left ventricle to accurately assess whether the left bundle branch was blocked and the block level, while the remaining 33 patients were not mapped. Patients with true LBBB achieved CRT by LBBAP, while patients with pseudo-LBBB achieved CRT by CVP. After a mean follow-up of 6 months and 1 year, the QRS duration and transthoracic echocardiography, including mechanical synchrony indices, were evaluated. Results: Twenty-five patients with true LBBB received LBBAP, while 13 without true LBBB received CVP. Seventeen patients received LBBAP, and 16 patients received CVP without mapping. Paced QRS duration after the implantation of LBBAP and CVP was significantly narrower in the mapping subgroup compared to the non-mapping subgroup. A significant increase in post-implantation left ventricular ejection fraction was observed in patients with LBBAP or CVP, and the mapping subgroup were better than the non-mapping subgroup. After a 12-month follow-up, atrioventricular, intraventricular, and biventricular synchronization were significantly improved in the mapping subgroup compared to non-mapping groups in both LBBAP and CVP. Conclusion: In our study, three-dimensional electroanatomical mapping was used to choose LBBAP or CVP for heart failure patients, which proved feasible, with better cardiac resynchronization in the long-term follow-up. Therefore, three-dimensional electroanatomical mapping before CRT appears to be a reliable method for heart failure patients with LBBB who are indicated for CRT.

[Non-targeted metabolomics study and biomarker screening of prehypertensive liver-fire hyperactivity syndrome based on UPLC-Q-Exactive MS technology].

In this study, patients with prehypertensive liver-fire hyperactivity syndrome(LFHS) were selected as the research objects. The plasma samples of healthy volunteers and patients with prehypertensive LFHS were analyzed by non-targeted metabolomics based on UPLC-Q-Exactive MS. The differential biomarkers and metabolic pathways were screened out by multivariate statistics and metabolic pathway analysis, which revealed the characteristics of metabolic patterns of the syndrome. Thirty-three potential biomarkers such as androsterone and lysophosphatidylcholine and 16 related metabolic pathways such as steroid hormone metabolism and lipid metabolism were identified, and a partial least squares-discriminant analysis(PLS-DA) model of traditional Chinese medicine(TCM) syndromes was preliminarily constructed: Y =-0.070X_(13)-0.006X_8+ 0.040X_5-0.152X_1+0.131X_(10)+0.036X_(11)+0.043X_(23)+0.076X_(16)+0.132X_(20)+0.081X_(19)-0.101X_(31)+0.082X_(15)-0.038X_9+0.079X_(24). The predictive value of the model was 88.1%, and the explanatory power was 88.4%. In this study, the characteristic metabolic pattern of the prehypertensive LFHS was distinguished and revealed by metabolomics. The constructed PLS-DA model is expected to provide an objective basis for the identification of TCM syndromes in prehypertension, and inspiration for exploring the biological basis of TCM syndromes at small-molecular and overall levels.

Design, synthesis and evaluation of tetrahydrocarbazole derivatives as potential hypoglycemic agents.

Two series of tetrahydrocarbazole derivatives have been designed and synthesized based on ZG02, a promising candidate developed in our previous studies. The newly prepared compounds were screened for glucose consumption activity in HepG2 cell lines. Aza-tetrahydrocarbazole compound 12b showed the most potent hypoglycemic activity with a 45% increase in glucose consumption when compared to the solvent control, which had approximately 1.2-fold higher activity than the positive control compounds (metformin and ZG02). An investigation of the potential mechanism indicated that 12b may exhibit hypoglycemic activity via activation of the AMPK pathway. Metabolic stability assays revealed that 12b showed good stability profiles in both artificial gastrointestinal fluids and blood plasma from SD rats. An oral glucose tolerance test (OGTT) was performed and the results further confirmed that 12b was a potent hypoglycemic agent.

Association between microRNA 25 expression in serum and lung cancer: A protocol for systematic review and meta-analysis.

BACKGROUND: This study aims to identify the association between microRNA 25 (mRNA 25) expression in serum and lung cancer (LC). METHODS: This planned study will cover all eligible case-controlled studies that report association between mRNA 25 expression in serum and LC. It will include published studies from inception to the present in Cochrane Library, PUBMED, EMBASE, Web of Science, Allied and Complementary Medicine Database, VIP database, and China National Knowledge Infrastructure regardless language and geographical location. We will also search other sources, such as conference abstracts and reference lists of related known studies and experts in the domain consulted to avoid missing potential studies. Two contributors will independently examine and select studies, collect all necessary data, and judge study quality for all included studies. We will perform statistical analysis using RevMan V.5.3 software and Stata V.12.0 software. RESULTS: This study will summarize current evidence to present first systematic review of research on the association between mRNA 25 expression in serum and LC. CONCLUSION: This study will present comprehensive evidence to determine whether mRNA 25 expression in serum is associated with LC, and will provide helpful evidence for the future studies. SYSTEMATIC REVIEW REGISTRATION: INPLASY202040056.

Early oral nutrition improves postoperative ileus through the TRPA1/CCK1-R-mediated mast cell-nerve axis.

BACKGROUND: The mechanism of early oral nutrition that regulates the mast cell-nerve axis to improve postoperative ileus (POI) remains unclear. This study aims to investigate whether early oral nutrition can improve POI through Transient receptor potential ankyrin-1 (TRPA1)/cholecystokinin 1 receptor (CCK1-R) in the mast cell-nerve axis. METHODS: Experiment 1: Male Sprague-Dawley (SD) rats were randomly divided into the TRPA1 inhibitor + oral nutrition group (TI + ON + POI), oral nutrition group (ON + POI), POI group (POI) and sham surgery group (Sham). Nine rats in each group were treated. Experiment 2: Primary cultures of mast cells and dorsal root ganglion cells were created, and a non-contact co-culture system was established. The cells were divided into the dorsal root ganglion (DRG) group, mast cell group, DRG + mast cell group, TRPA1 inhibitor or enhancer group, mast cell stabilizer or enhancer group, CCK1-R inhibitor or enhancer group. The results of expression of TRPA1, CCK1-R and histamine in colon tissue, portal vein blood, supernatant or dorsal root ganglia, intestinal transport test and mast cell morphology were analysed. RESULTS: In experiment 1, Early oral nutrition could alleviate the degranulation and activation of mast cells and alleviate the inflammatory reaction of intestinal wall muscles (P<0.05). Early oral nutrition improved POI by stabilizing mast cells with TRPA1. TRPA1 inhibitor decreased CCK1-R concentrations in portal vein blood and CCK1-R expression in colonic smooth muscle (P<0.05). In experiment 2, the change in mast cell function regulated the secretion of CCK1-R by neurons, CCK1-R negatively regulated the degranulation and activation of mast cells (P<0.05), and mast cells positively regulated the expression of TRPA1 protein in DRG (P<0.05). CONCLUSIONS: Early enteral nutrition can improve POI through the TRPA1/CCK1-R-mediated mast cell-nerve axis. TRPA1 positively regulates CCK1-R to stabilize mast cells, but TRPA1 is not the target of the downstream CCK1-R pathway.

Screening and combining serum biomarkers to improve their diagnostic performance in the detection of intestinal barrier dysfunction in patients after major abdominal surgery.

BACKGROUND: The aim of this prospective study was to screen and combine effective biomarkers to improve their diagnostic performance in detecting intestinal barrier dysfunction in patients after major abdominal surgery. METHODS: Patients undergoing major abdominal surgery were enrolled after signing informed consent in this study. The serum concentrations of α-GST, DAO, D-lactate, citrulline and I-FABP were detected 24 hours before and after surgery. The diagnostic performance of five biomarkers on intestinal barrier dysfunction was assessed using logistic regression models and receiver operating characteristic (ROC) curve analyses. RESULTS: Thirty-nine patients with major abdominal surgery were enrolled in and successfully completed this study. ROC analysis revealed that the sensitivities of D-lactate, citrulline and I-FABP were very high (0.91, 0.91 and 1.00, respectively), but the specificities of these biomarkers were less than 0.70. The sensitivity of DAO was very low [0.25; 95% confidence interval (CI), 0.05-0.57], but its specificity was high (0.92; 95% CI, 0.75-0.99). The accuracies of D-lactate and I-FABP were very high, and the areas under the curves (AUCs) of the biomarkers were 0.84 (95% CI, 0.68-0.93) and 0.81 (95% CI, 0.65-0.92), respectively. Different combinations of five biomarkers were also analysed. The sensitivity, specificity and AUC values of the combination of I-FABP, citrulline and D-lactate were 1.00, 0.74 and 0.89, respectively. These results were similar to those derived from the combination of α-GST, DAO, D-lactate, citrulline and I-FABP (P=1.000). CONCLUSIONS: The combination of serum D-lactic acid, citrulline and I-FABP greatly improved the diagnostic performance for identifying intestinal barrier dysfunction in patients after major abdominal surgery.

[Acupuncture of intraorbital and extraorbital acupoints reduces apoptosis of retinal ganglion by down-regulating expression of Caspase-3 and ratio of Bax/Bcl-2 in rabbits with nonarteritis anterior ischemic optic neuropathy].

OBJECTIVE: To observe the effect of acupuncture of intraorbital and extraorbital acupoints on apoptosis and expression of Bax, Bcl-2 and Caspase-3 proteins of retinal ganglion tissue in rabbits with nonarteritis anterior ischemic optic neuropathy (NAION), so as to reveal its mechanism underlying improvement of NAION. METHODS: Female New Zealand rabbits were randomly divided into four groups: model, intraocular needling (ION), extraocular needling (EON), ION＋EON groups (n＝5 per group), and the 5 healthy eyes of those rabbits in the model group were selected to be used as the control group. The NAION model of the right eye was established by photodynamic stroke method. For ION group, acupoints "Jingming" (BL1), "Chengqi" (ST1) and "Qiuhou" (EX-HN7) were needled, and for EON group, "Cuanzhu" (BL2), "Yuyao" (EX-HN4) and "Qiaoming" (EX) were needled with filiform needles, followed by retaining the needles for 30 min. For ION＋EON group, the 6 acupoints were needled simutaneously. The treatment was conducted once daily for 3 days. The apoptosis of retinal ganglion tissue was detected by using TUNEL fluorescence labeling, and the expression of Bax, Bcl-2 and active Caspase-3 in the retinal ganglion were detected by immunohistochemistry. RESULTS: Following modeling and compared with the control group, the number of the apoptotic cells, and the expression levels of Bax and Caspase-3 proteins, as well as the ratio of Bax/Bcl-2 were significantly increased in the model group (P<0.01), while the expression of Bcl-2 was significantly decreased (P<0.01). After intervention, the number of the apoptotic cells in the ION, EON and ION＋EON groups, and the ratio of Bax/Bcl-2 in EON and ION＋EON groups, and the expression of Caspase-3 proteins in the ION and ION＋EON groups were significantly down-regulated (P<0.01, P<0.05), and the expression levels of Bcl-2 in both EON and ION＋EON groups were significantly up-regulated in comparison with the model group (P<0.01). No significant changes were found in the expression levels of Bax in the 3 needling groups relevant to the model group (P>0.05). CONCLUSION: Acupuncture of intraorbital and extraorbital acupoints can reduce apoptosis of retinal ganglion in NAION rabbits via inhibiting the activation of Caspase-3 protein and ratio of Bax/Bcl-2, and up-regulating the expression of Bcl-2 protein.

[Randomized controlled clinical trial of acupuncture treatment for knee osteoarthritis in the early stage].

OBJECTIVE: To observe the therapeutic effect of acupuncture in the treatment of patients with knee osteoarthritis (KOA) in the early stage. METHODS: A total of 60 KOA patients were randomized into medication group and acupuncture combined with medication (acupuncture) group (n＝ 30 in each group). Patients of the medication group were treated by external application of Diclofenac Diethylamine Emulgel around the affected joint, 3 times a day for 2 successive weeks and reasonable exercising training. Patients of the acupuncture group received routine medication and reasonable exercising training and acupuncture of Ashi-points, Zusanli (ST36), Yanglingquan (GB34), Yinlingquan (SP9), Neixiyan (EX-LE4) and Dubi (ST35) at affected side with filiform needles which were manipulated with uniform reinforcing-reducing method for a while, followed by retaining the needles for 30 min. The treatment was conducted once every other day for 2 weeks. The pain degree was assessed by using visual analog scale (VAS) and the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) scale (0－240 points) was used to evaluate the severity of KOA, and the "Diagnosis of Syndromes of Traditional Chinese Medicine" was used to assess the therapeutic effect after the treatment. RESULTS: After the treatment, the VAS and WOMAC scores of both medication and acupuncture groups were significantly and respectively decreased in comparison with their own pre-treatment (P<0.05), and the scores of the two indexes of the acupuncture group were evidently lower than those of the medication group (P<0.05). Of the two 30 cases in the medication and acupuncture groups, 5 (16.67%) and 6 (20.00%) were cured, 17 (56.67%) and 19 (63.33%) experienced marked improvement, 6 (20.00%) and 4 (13.33%) were effective, 2 (6.67%) and 1 (3.33%) were ineffective, with the effective rate of cure plus marked effectiveness being 73.33% and 83.33%, respectively. No significant difference was found between the two groups in the therapeutic effect (P>0.05). CONCLUSION: Acupuncture combined with medication has a better therapeutic effect in the treatment of KOA in the early stage than that of the simple medication.

Efficacy of pirfenidone for the treatment of pulmonary fibrosis: An updated systematic review protocol of randomized controlled trial.

BACKGROUND: This study will systematically assess the efficacy and safety of pirfenidone for the treatment of patients with pulmonary fibrosis (PF). METHODS: We will search potential records from following literature sources from their inceptions to the present without language, and publication status limitations: Cochrane Library, EMBASE, PUBMED, the Cumulative Index to Nursing and Allied Health Literature, the Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. In addition, we also search grey literature sources, such as dissertations, conference proceedings, as well as the reference lists of included studies. All randomized controlled trials related to the pirfenidone for treating PF will be included. All the process of study selection, data extraction, and methodological evaluation will be carried out by 2 authors independently. The primary outcome comprises of all-cause-mortality, and lung function status, as measured by forced vital capacity. The secondary outcomes consist of 6-minute walk distance, progression-free survival, dyspnea, acute exacerbation, quality of life, and adverse events. Whenever possible, all results data will be pooled and meta-analysis will be performed. RESULTS: This study will systematically assess the efficacy and safety of pirfenidone for the treatment of patients with PF. CONCLUSION: The findings of the present study will summarize most recent evidence of pirfenidone for PF. ETHICS AND DISSEMINATION: No individual data will be analyzed in this study, thus, no research ethics approval is required in this study. The findings of this study are expected to be disseminated in a peer-reviewed journal or conference presentations. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42019126958.

Characterization of the Multi-Drug Resistance Gene cfr in Methicillin-Resistant Staphylococcus aureus (MRSA) Strains Isolated From Animals and Humans in China.

We investigated cfr-positive and -negative MRSA strains isolated from animals and humans in different geographical areas of China, from 2011 to 2016. Twenty cfr-positive strains (15.6%) were identified from 128 MRSA strains including 17 from food animals and three from humans. The resistance rates and prevalence of the tested antibiotic resistance genes (ARGs) in the cfr-positive MRSA isolates were higher than that in the cfr-negative MRSA isolates. All cfr-positive MRSA isolates were co-carrying fexA and ermC, and had significantly higher optrA incidence rate vs. the cfr-negative isolates (P < 0.05). In addition, multilocus sequence typing (MLST) assays showed that ST9 and spa-type t899 were the most prevalent ST and spa types in the study strains. However, all of the 20 cfr-positive and 10 randomly selected cfr-negative MRSA isolates were clonally unrelated as determined by pulsed-field gel electrophoresis (PFGE) analyses. Importantly, the cfr gene was successfully transferred to a recipient Staphylococcus aureus strain RN4220 from 13 of the 20 cfr-positive MRSA isolates by electroporation. Among these 13 cfr-positive MRSA isolates, two different genetic contexts surrounding cfr were determined and each was associated with one type of cfr-carrying plasmids. Of note, the predominant genetic context of cfr was found to be a Tn558 variant and locate on large plasmids (∼50 kb) co-harboring fexA in 11 of the 13 MRSA isolates. Furthermore, the cfr gene was also identified on small plasmids (∼ 7.1 kb) that co-carried ermC in two of the 13 MRSA isolates. Our results demonstrated a high occurrence of multi-drug resistance in cfr-positive MRSA isolates, and the spread of cfr might be attributed to horizontal dissemination of similar cfr-carrying transposons and plasmids.

Biomechanical properties of novel transpedicular transdiscal screw fixation with interbody arthrodesis technique in lumbar spine: A finite element study.

PURPOSE: The purpose of this study was to investigate finite element biomechanical properties of the novel transpedicular transdiscal (TPTD) screw fixation with interbody arthrodesis technique in lumbar spine. METHODS: An L4-L5 finite element model was established and validated. Then, two fixation models, TPTD screw system and bilateral pedicle screw system (BPSS), were established on the validated L4-L5 finite element model. The inferior surface of the L5 vertebra was set immobilised, and moment of 7.5 Nm was applied on the L4 vertebra to test the range of motion (ROM) and stress at flexion, extension, lateral bending and axial rotation. RESULTS: The intact model was validated for prediction accuracy by comparing two previously published studies. Both of TPTD and BPSS fixation models displayed decreased motion at L4-L5. The ROMs of six moments of flexion, extension, left lateral bending, right lateral bending, left axial rotation and right axial rotation in TPTD model were 1.92, 2.12, 1.10, 1.11, 0.90 and 0.87°, respectively; in BPSS model, they were 1.48, 0.42, 0.35, 0.38, 0.74 and 0.75°, respectively. The screws' peak stress of above six moments in TPTD model was 182.58, 272.75, 133.01, 137.36, 155.48 and 150.50 MPa, respectively; and in BPSS model, it was 103.16, 129.74, 120.28, 134.62, 180.84 and 169.76 MPa, respectively. CONCLUSION: Both BPSS and TPTD can provide stable biomechanical properties for lumbar spine. The decreased ROM of flexion, extension and lateral bending was slightly more in BPSS model than in TPTD model, but TPTD model had similar ROM of axial rotation with BPSS model. The screws' peak stress of TPTD screw focused on the L4-L5 intervertebral space region, and more caution should be put at this site for the fatigue breakage. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Our finite element study provides the biomechanical properties of novel TPTD screw fixation, and promotes this novel transpedicular transdiscal screw fixation with interbody arthrodesis technique be used clinically.

[ACE2 agonist DIZE alleviates lung injury induced by limb ischemia-reperfusion in mice].

This study was aimed to explore the effect of angiotensin converting enzyme 2 (ACE2) agonist diminazene aceturate (DIZE) on acute lung injury (ALI) induced by limb ischemia-reperfusion (LIR) in mice. Male 8-week-old wild-type and hACE2 transgenic ICR mice were randomly divided into 6 groups (6 in each group), including wild-type control (W), wild-type model (WL), wild-type model with DIZE administration (WLD), transgenic control (T), transgenic model (TL), and transgenic model with DIZE administration (TLD) groups. LIR model was established by 4 h reperfusion following 2 h ischemia of bilateral hindlimbs with rubber bands in mice. The WLD and TLD groups were pretreated with DIZE (15 mg/kg, i.p.) for 4 weeks before LIR. At the end of LIR, the mice were sacrificed and lung tissues were sampled. Indexes for evaluating lung injury include organ coefficient and wet/dry weight ratio (W/D), cell count and protein concentration of bronchoalveolar lavage fluid (BALF), as well as morphological change and pathological score were detected. Angiotensin II (Ang II) and Ang (1-7) levels in lung tissue were determined by using ELISA commercial kits. And the protein expressions of angiotensin II type 1 receptor (AT1) and Mas receptor protein in lung tissue were detected by Western blot. The results were as follows: (1) There was obvious lung injury in both the WL and TL groups. The lung injury in the TL group was lighter than that in the WL group. DIZE could attenuate the lung injury in both the two groups. (2) The WL group showed increased Ang II and decreased Ang (1-7) levels, whereas the TL group did not exhibit any changes of these two proteins. DIZE decreased the level of Ang II in both the WL and TL groups, and increased the level of Ang (1-7) in the WL group. (3) In the WL and TL groups, AT1 and Mas receptor protein expressions were up-regulated. DIZE reversed the change of AT1 protein expression, whereas further increased Mas receptor expression in both the two groups. These results suggest that DIZE may improve the renin-angiotensin system homeostasis by regulating ACE2-Ang (1-7)-Mas axis in local lung tissue and play a protective role in LIR-induced ALI in mice.

Discovery of tetrahydrocarbazoles with potent hypoglycemic and hypolipemic activities.

A series of tetrahydrocarbazole derivatives was designed and synthesized on the basis of the AMP-activated protein kinase activator GY3. All the synthesized compounds were screened in HepG2 cell lines for glucose consumption activity and several of them showed potent glucose decreasing activity. In vivo evaluation of the hypoglycemic and hypolipemic effects indicated that 7a exhibited comparable activity with pioglitazone, but with a weaker body-weight increasing effect. The pharmacokinetic profiles of 7a were also investigated.

Neoadjuvant Bleomycin, Etoposide, and Cisplatin (BEP) Chemotherapy in the Treatment of Extensively Advanced Yolk Sac Tumors: A Single Center Experience.

OBJECTIVE: This study aimed to investigate the role of neoadjuvant bleomycin, etoposide, and cisplatin (BEP) regimen in patients with extensively advanced yolk sac tumors (YSTs). METHODS: Between July 1982 and December 2015, a total of 58 patients with YST were initially treated at our institution, among which 18 were evaluated to be inoperable and received neoadjuvant BEP regimen. They were either too debilitated by the disease [Eastern Cooperative Oncology Group Performance Status Scale (ECOG ps) ≥2] to undergo a major surgery or were with too extensively disseminated lesions to be optimally debulked. This cohort of patients was retrospectively reviewed. RESULTS: One or 2 cycles of BEP regimen were prescribed to the majority of patients preoperatively. At the completion of neoadjuvant chemotherapy, 17 of them had ECOG ps of 1 or less. Seventeen (94.4%) exhibited clinical partial tumor regression, and 1 (5.6%) had clinical stable disease. Pathological complete tumor regression was observed in 2 (11.1%) patients, whereas the remaining 16 (88.9%) had nearly complete pathological regression. Seventeen patients were cytoreduced to no macroscopic residual disease; the remaining 1 was cytoreduced to macroscopic residual disease of 2 cm or less. No major surgical complications occurred. After a median follow-up of 83.5 months, 17 patients were free of recurrence. Five-year disease-free survival and overall survival were both 94.4%. Fertility-sparing surgery was carried out in all the 17 patients with the desire to preserve their fertility, and 5 infants were delivered in 6 patients who attempted conception. CONCLUSIONS: One or 2 cycles of neoadjuvant BEP regimen followed by cytoreductive surgery offer a chance for cure in extensively advanced patients with YSTs and help pave the way for fertility-sparing surgery.