A comparative study of three internal fixation techniques for split fractures of humeral greater tuberosity / 中华创伤骨科杂志

Objective:To compare the clinical effectiveness between arthroscopic hollow screws combined with a suture anchor, hollow screws and proximal humerus internal locking system (PHILOS) in the treatment of split-type fractures of humeral greater tuberosity.Methods:A retrospective study was conducted to analyze the 54 patients with split-type fracture of humeral greater tuberosity who had been admitted to Department of Joint Surgery, Hospital of Traditional Chinese Medicine, Affiliated to Southwest Medical University from May 2015 to August 2020. There were 17 males and 37 females with an age of (58.4±12.1) years. According to different treatment methods, they were divided into 3 groups. Group A of 18 cases was treated with arthroscopic hollow screws combined with a suture anchor, group B of 18 cases with hollow screws, and group C of 18 cases with PHILOS. The length of surgical incision, and range of shoulder motion, visual analogue scale (VAS), and American Shoulder and Elbow Surgeons (ASES) score at the last follow-up were recorded and compared between the 3 groups.Results:There was no statistically significant difference in the preoperative general information between the 3 groups, indicating the 3 groups were comparable ( P>0.05). The surgical incision in group A [(0.7±0.1) cm] was the shortest, followed by (5.0±1.4) cm in group B, and (12.8±2.1) cm in group C, showing statistically significant differences in pairwise comparison ( P<0.05). In the 3 groups at the last follow-up, respectively, the shoulder forward flexion was 159.7°±13.4°, 154.9°±16.2°, and 160.5°±12.9°, and the shoulder abduction 149.6°±11.3°, 142.4°±12.0°, and 145.1°±10.4°, showing no statistically significant difference among the 3 groups ( P>0.05); the external rotation was 41.1°±8.1°, 38.1°±7.8° and 43.7°±6.2°, showing a statistically significant difference between groups B and C ( P<0.05); the dorsal extension was T 12 (L 5 to T 6), T 12 (L 5 to T 7), and T 12 (L 3 to T 6), showing no statistically significant difference among the 3 groups ( P>0.05). There was no statistically significant difference among the 3 groups in the VAS score or ASES score at the last follow-up ( P>0.05). Respectively, there were 2, 6, and 4 patients in groups A, B and C who developed complications, showing statistically significant differences between the 3 groups ( P<0.05). Conclusions:In the treatment of split fractures of humeral greater tuberosity, arthroscopic hollow screws combined with a suture anchor, hollow screws and PHILOS can all relieve pain and restore joint function of the shoulder. However, arthroscopic hollow screws combined with a suture anchor are the most recommendable due to their advantages in minimally invasiveness and reduction in complications.

Saphenous vascular periosteal flap in prevention of bone bridge formation after epiphyseal plate injury: An experimental study / 中华显微外科杂志

Objective:To establish a model of epiphyseal plate injury in juvenile rabbits and explore the effect of periosteum flap with saphenous artery on preventing the formation of bone bridge after epiphyseal plate injury.Methods:From July 2017 to January 2018, 30 young New Zealand immature rabbit were randomly grouped into 3 groups (group A, B and C, with 10 rabbits per group). The blood vessels of knee joint were dissected and a periosteum flap with saphenous artery were designed. A model of distal femoral epiphyseal plate injury was established in immature rabbits with a 3.0 mm Kirschner wire on one side of the distal femoral epiphyseal plate as experimental side, and the other side of the distal femoral epiphyseal plate was assigned as control side. The injured epiphysis were prepared and described as follow: in experimental side of group A, a piece of periosteum with the same size as that in group C was resected and discarded. In experimental side of group B, a periosteal flap without vascular pedicle was filled in the injured area. And in experimental side of group C, a periosteum flap with saphenous artery was filled in the injured area. The length and varus angle of femur specimens of length and varus angle of femur specimens wihthin groups were measured at 24 weeks after surgery to evaluate the effect on bone growth in epiphyseal plate injury. The effect of the periosteum flap with saphenous artery on preventing a formation of bone bridge was assessed by section view of decalcified specimens, HE staining and toluidine blue staining. The measured data were expressed as Mean and standard deviation (Mean±SD), and data were compared within and between the groups using one-way analysis of variance (ANOVA). P<0.05 was considered as statistically significant. Results:The femur of experimental side of group A and B showed obvious short with valgus deformity compared with that of control side, and the difference of length and varus angle of femur specimens wihthin groups was statistically significant ( P<0.05). There were no significant differences in the length and valgus angle of the femur between experimental side and its control side in group C ( P>0.05). In experimental side of group A, there were bone bridges in the epiphyseal lesion area, with a clear boundary to the surrounding epiphyseal plate. In experimental side of group B, the periosteum flap in the injured area was absorbed, accompanied by the formation of a few pale white bone tissue, and with a clear boundary to the surrounding epiphyseal plate. In experimental side of group C, the lesion area was filled with milky white cartilage tissue with the same colour as the epiphyseal plate, and with an unclear boundary with the epiphyseal plate. HE stain and toluidine blue staining showed that the injured area of group A was filled with a large number of bone tissue, but no obvious cartilage tissue was observed. In group B, the area of lesion was filled mainly with fibrous tissue, with a small amount of bone tissue. In group C, a large number of hyaline cartilage tissues were formed along the tunnel of the injury area, and closely connected with the normal epiphyseal plate. Conclusion:Filling a periosteum flap with saphenous artery after epiphyseal plate injury can prevent the formation of bone bridge and prevent the affected limb form shortening and angulation.

A human monoclonal antibody potently pan-neutralizes SARS-CoV-2 VOCs by targeting RBD invariant sites

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel corona virus disease (COVID-19). The neutralizing monoclonal antibodies (mAbs) targeting the receptor binding domain (RBD) of SARS-CoV-2 are among the most promising strategies to prevent and treat COVID-19. However, SARS-CoV-2 variants of concern (VOCs) profoundly reduced the efficacies of most of mAbs and vaccines approved for clinical use. Herein, we demonstrated mAb 35B5 efficiently neutralizes both wild-type (WT) SARS-CoV-2 and VOCs, including B.1.617.2 (delta) variant, in vitro and in vivo. Cryo-electron microscopy (cryo-EM) revealed that 35B5 neutralizes SARS-CoV-2 by targeting a unique epitope that avoids the prevailing mutation sites on RBD identified in circulating VOCs, providing the molecular basis for its pan-neutralizing efficacy. The 35B5-binding epitope could also be exploited for the rational design of a universal SARS-CoV-2 vaccine.

Acquisition of the L452R mutation in the ACE2-binding interface of Spike protein triggers recent massive expansion of SARS-Cov-2 variants

The recent rise in mutational variants of SARS-CoV-2, especially with changes in the Spike protein, is of significant concern due to the potential ability for these mutations to increase viral infectivity, virulence and/or ability to escape protective antibodies. Here, we investigated genetic variations in a 414-583 amino acid region of the Spike protein, partially encompassing the ACE2 receptor-binding domain (RBD), across a subset of 570 nasopharyngeal samples isolated between April 2020 and February 2021, from Washington, California, Arizona, Colorado, Minnesota and Illinois. We found that samples isolated since November have an increased number of amino acid mutations in the region, with L452R being the dominant mutation. This mutation is associated with a recently discovered CAL.20C viral variant from clade 20C, lineage B.1.429, that since November-December 2020 is associated with multiple outbreaks and is undergoing massive expansion across California. In some samples, however, we found a distinct L452R-carrying variant of the virus that, upon detailed analysis of the GISAID database genomes, is also circulating primarily in California, but emerged even more recently. The newly identified variant derives from the clade 20A (lineage B.1.232) and is named CAL.20A. We also found that the SARS-CoV-2 strain that caused the only recorded case of infection in an ape - gorillas in the San Diego Zoo, reported in January 2021 - is CAL.20A. In contrast to CAL.20C that carries two additional to L452R mutations in the Spike protein, L452R is the only mutation found in CAL.20A. According to the phylogenetic analysis, however, emergence of CAL.20C was also specifically triggered by acquisition of the L452R mutation. Further analysis of GISAID-deposited genomes revealed that several independent L452R-carrying lineages have recently emerged across the globe, with over 90% of the isolates reported between December 2020 - February 2021. Taken together, these results indicate that the L452R mutation alone is of significant adaptive value to SARS-CoV-2 and, apparently, the positive selection for this mutation became particularly strong only recently, possibly reflecting viral adaptation to the containment measures or increasing population immunity. While the functional impact of L452R has not yet been extensively evaluated, leucine-452 is positioned in the receptor-binding motif of RBD, in the interface of direct contact with the ACE2 receptor. Its replacement with arginine is predicted to result in both a much stronger binding to the receptor and escape from neutralizing antibodies. If true, this in turn might lead to significantly increased infectivity of the L452R variants, warranting their close surveillance and in-depth functional studies.

Environmental monitoring shows SARS-CoV-2 contamination of surfaces in food plants

The SARS-CoV-2 pandemic has presented new challenges to food manufacturers. In addition to preventing the spread of microbial contamination of food, with SARS-CoV-2, there is an additional focus on preventing SARS-CoV-2 infections in food plant personnel. During the early phase of the pandemic, several large outbreaks of Covid-19 occurred in food manufacturing plants resulting in deaths and economic loss. In March of 2020, we assisted in implementation of environmental monitoring programs for SARS-CoV-2 in 116 food production facilities. All participating facilities had already implemented measures to prevent symptomatic personnel from coming to work. During the study period, from March 17, 2020 to September 3, 2020, 1.23% of the 22,643 environmental samples tested positive for SARS-CoV-2, suggesting that infected individuals are actively shedding virus. Virus contamination was commonly found on frequently touched surfaces. Most plants managed to control their environmental contamination when they became aware of the positive findings. Comparisons of the personnel test results to environmental contamination in one plant showed a good correlation between the two. Our work illustrates that environmental monitoring for SARS-CoV-2 can be used as a surrogate for identifying the presence of asymptomatic and pre-symptomatic personnel in workplaces and may aid in controlling infection spread. HighlightsO_LIEnvironmental contamination by SARS-CoV-2 virus was detected in food plants C_LIO_LIOut of 22,643 environmental swabs, 278 (1.23%) were positive for SARS-CoV-2 C_LIO_LIFrequently touched surfaces had the most contamination C_LIO_LISurface testing for SARS-CoV-2 may indicate presence of asymptomatic carriers C_LI

Disease severity dictates SARS-CoV-2-specific neutralizing antibody responses in COVID-19

COVID-19 patients exhibit differential disease severity after SARS-CoV-2 infection. It is currently unknown as to the correlation between the magnitude of neutralizing antibody (NAb) responses and the disease severity in COVID-19 patients. In a cohort of 59 recovered patients with disease severity including severe, moderate, mild and asymptomatic, we observed the positive correlation between serum neutralizing capacity and disease severity, in particular, the highest NAb capacity in sera from the patients with severe disease, while a lack of ability of asymptomatic patients to mount competent NAbs. Furthermore, the compositions of NAb subtypes were also different between recovered patients with severe symptoms and with mild-to-moderate symptoms. These results reveal the tremendous heterogeneity of SARS-CoV-2-specific NAb responses and their correlations to disease severity, highlighting the needs of future vaccination in COVID-19 patients recovered from asymptomatic or mild illness.

Human monoclonal antibodies block the binding of SARS-CoV-2 spike protein to angiotensin converting enzyme 2 receptor

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel corona virus disease (COVID-19). To date, no prophylactic vaccines or approved therapeutic agents are available for preventing and treating this highly transmittable disease. Here we report two monoclonal antibodies (mAbs) cloned from memory B cells of patients recently recovered from COVID-19, and both mAbs specifically bind to the spike (S) protein of SARS-CoV-2, block the binding of receptor binding domain (RBD) of SARS-CoV-2 to human angiotensin converting enzyme 2 (hACE2), and effectively neutralize S protein-pseudotyped virus infection. These human mAbs hold the promise for the prevention and treatment of the ongoing pandemic of COVID-19.

Pulse Wave Velocity Is Associated with Increased Plasma oxLDL in Ageing but Not with FGF21 and Habitual Exercise.

Fibroblast growth factor 21 (FGF21) and adiponectin increase the expression of genes involved in antioxidant pathways, but their roles in mediating oxidative stress and arterial stiffness with ageing and habitual exercise remain unknown. We explored the role of the FGF21-adiponectin axis in mediating oxidative stress and arterial stiffness with ageing and habitual exercise. Eighty age- and sex-matched healthy individuals were assigned to younger sedentary or active (18-36 years old, n = 20 each) and older sedentary or active (45-80 years old, n = 20 each) groups. Arterial stiffness was measured indirectly using pulse wave velocity (PWV). Fasted plasma concentrations of FGF21, adiponectin and oxidized low-density lipoprotein (oxLDL) were measured. PWV was 0.2-fold higher and oxLDL concentration was 25.6% higher (both p < 0.001) in older than younger adults, despite no difference in FGF21 concentration (p = 0.097) between age groups. PWV (p = 0.09) and oxLDL concentration (p = 0.275) did not differ between activity groups but FGF21 concentration was 9% lower in active than sedentary individuals (p = 0.011). Adiponectin concentration did not differ by age (p = 0.642) or exercise habits (p = 0.821). In conclusion, age, but not habitual exercise, was associated with higher oxidative stress and arterial stiffness. FGF21 and adiponectin did not differ between younger and older adults, meaning that it is unlikely that they mediate oxidative stress and arterial stiffness in healthy adults.

Precautions are Needed for COVID-19 Patients with Coinfection of Common Respiratory Pathogens

BackgroundWith the ongoing outbreak of Coronavirus Disease 2019 (COVID-19), infected patients within and beyond the epidemic area, Wuhan, China, showed different epidemiological and clinical characteristics. There is a paucity of data concerning coinfection with other common respiratory pathogens in COVID-19 patients outside of Wuhan. MethodsWe conducted a double-centre study recruiting 68 patients with severe acute respiratory coronavirus 2 (SARS-CoV-2) infection confirmed by nucleic acid testing in Qingdao and Wuhan from January 17 to February 16, 2020. Indirect immunofluorescence was performed to detect the specific IgM antibody against common respiratory pathogens in collected acute phase serum. ResultsOf the 68 patients with SARS-CoV-2 infection, 30 (44.12%) were from Qingdao. The median age of Qingdao and Wuhan patients were 50 (IQR: 37-59) and 31 (IQR: 28-38) years, respectively, and the majority of patients were female in Qingdao (60.00%) and Wuhan (55.26%). Among COVID-19 patients in Qingdao, 24 (80.00%) of them had IgM antibodies against at least one respiratory pathogen, whereas only one (2.63%) of the patients in Wuhan had positive results for serum IgM antibody detection (P<0.0001). The most common respiratory pathogens detected in Qingdao COVID-19 patients were influenza virus A (60.00%) and influenza virus B (53.33%), followed by mycoplasma pneumoniae (23.33%) and legionella pneumophila (20.00%). While the pattern for coinfection in patients with community-acquired pneumonia in Qingdao was quite different, with a positive rate of only 20.90%. InterpretationWe reported a large proportion of COVID-19 patients with coinfection of seasonal respiratory pathogens in Qingdao, northeast China, which differed greatly from the patients in Wuhan, central China. Precautions are needed when dealing with COVID-19 patients beyond the epidemic centre who have coinfection with other respiratory pathogens. We highly recommend adding SARS-CoV-2 to routine diagnostic testing in capable hospitals to prevent misdetection of the virus.

Teicoplanin potently blocks the cell entry of 2019-nCoV

Since the outbreak of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the public health worldwide has been greatly threatened. The development of an effective treatment for this infection is crucial and urgent but is hampered by the incomplete understanding of the viral infection mechanism and the lack of specific antiviral agents. We previously reported that teicoplanin, a glycopeptide antibiotic that has been commonly used in the clinic to treat bacterial infection, significantly restrained the cell entry of Ebola virus, SARS-CoV and MERS-CoV by specifically inhibiting the activity of cathepsin L (CTSL). Here, we found that the cleavage sites of CTSL on the Spike of SARS-CoV-2 were highly conserved among all the variants. The treatment with teicoplanin suppressed the proteolytic activity of CTSL on Spike and prevented the cellular infection of different pseudotyped SARS-CoV-2 viruses. Teicoplanin potently prevented the entry of authentic SARS-CoV-2 into the cellular cytoplasm with an IC50 of 2.038 M for the Wuhan-Hu-1 reference strain and an IC50 of 2.116 M for the SARS-CoV-2 (D614G) variant. The pre-treatment of teicoplanin also prevented SARS-CoV-2 infection in hACE2 mice. In summary, our data reveal that CTSL is required for both SARS-CoV-2 and SARS-CoV infection and demonstrate the therapeutic potential of teicoplanin for universal anti-CoVs intervention. ImportanceDisease prevention and treatment are two important countermeasures to end the coronavirus disease 2019 (COVID-19). However, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, evolves all the time, resulting in the emerging of many epidemic SARS-CoV-2 mutants, which significantly impairs the effectiveness of early strain-based vaccines and antibodies. Developing universal vaccines and broad-spectrum antiviral drugs are essential to confront SARS-CoV-2 mutants including those may emerge in the future. Our study reported here showed that the cleavage sites of cellular cathepsin L (CTSL) are highly conserved among all the SARS-CoV-2 mutants and SARS-CoV. The CTSL inhibitor teicoplanin not only inhibited the cell entry of two live SARS-CoV-2 strains and various pseudotyped viruses but also prevented live virus infection in animal models. Based on our previous finding that teicoplanin also inhibited SARS-CoV and MERS-CoV infection, we believe that teicoplanin possesses the potential to become a universal anti-CoVs drug.

Age-related bone loss is associated with FGF21 but not IGFBP1 in healthy adults.

What is the central question of this study? Fibroblast growth factor 21 (FGF21) plays important therapeutic roles in metabolic diseases but is associated with bone loss, through insulin-like growth factor binding protein 1 (IGFBP1), in animals. However, the effect of the FGF21-IGFBP1 axis on age-related bone loss has not been explored in humans. What is the main finding and its importance? Using 'genetically linked' parent and child family pairs, we show that the FGF21 concentration, but not the IGFBP1 concentration, is higher in older than in younger adults. Our results suggest that age-associated decline in bone mineral density is associated with FGF21 and increased bone turnover but not likely to involve IGFBP1 in healthy humans. ABSTRACT: Bone fragility increases with age. The fibroblast growth factor 21 (FGF21)-insulin-like growth factor binding protein 1 (IGFBP1) axis regulates bone loss in animals. However, the role of FGF21 in mediating age-associated bone fragility in humans remains unknown. The purpose of this study was to explore the FGF21-regulatory axis in bone turnover and the age-related decline in bone mineral density (BMD). Twenty 'genetically linked' family (parent and child) pairs were recruited. Younger adults were 22-39 years old and older adults 60-71 years old. The BMD and serum concentrations of FGF21, IGFBP1, receptor activator of nuclear factor-κB ligand (RANKL), tartrate-resistant acid phosphatase 5b (TRAP5b) and bone-specific alkaline phosphatase (BAP) were measured. Older adults had 10-18% lower BMD at the hip and spine (P < 0.008) and a twofold higher FGF21 concentration (P < 0.001). The IGFBP1 concentration was similar in younger and older adults (P = 0.961). The RANKL concentration was 44% lower (P = 0.006), whereas TRAP5b and BAP concentrations were 36 and 31% higher (P = 0.01 and P = 0.004), respectively, in older adults than in younger adults. Adjusting for sex did not affect these results. The FGF21 concentration was negatively correlated with BMD at the spine (r = -0.460, P = 0.003), but not with the IGFBP1 concentration (r = -0.144, P = 0.374). The IGFBP1 concentration was not correlated with BMD at the hip or spine (all P > 0.05). In humans, FGF21 might be involved in the age-associated decline in BMD, especially at the spine, through increased bone turnover. IGFBP1 is unlikely to be the downstream effector of FGF21 in driving the age-associated decline in BMD and in RANKL-associated osteoclast differentiation.

Fibroblast Growth Factor 21 Mediates the Associations between Exercise, Aging, and Glucose Regulation.

INTRODUCTION: Aging increases the prevalence of glucose intolerance, but exercise improves glucose homeostasis. The fibroblast growth factor 21 (FGF21)-adiponectin axis helps regulate glucose metabolism. However, the role of FGF21 in mediating glucose metabolism with aging and exercise remains unknown. PURPOSE: This study examined whether FGF21 responses to a glucose challenge are associated with habitual exercise, aging and glucose regulation. METHODS: Eighty age- and sex-matched healthy individuals were assigned to young sedentary and active (≤36 yr, n = 20 each group) and older sedentary and active (≥45 yr, n = 20 each group) groups. Fasted and postprandial blood glucose concentration and plasma concentration of insulin, FGF21, and adiponectin were determined during an oral glucose tolerance test (OGTT). RESULTS: During the OGTT, glucose concentrations were 9% higher (P = 0.008) and FGF21 concentrations were 58% higher (P = 0.014) in the older than the younger group, independent of activity status. Active participants had 40% lower insulin concentration and 53% lower FGF21 concentration than sedentary participants, independent of age (all P < 0.001). Adiponectin concentration during the OGTT did not differ by age (P = 0.448) or activity status (P = 0.611). Within the younger group, postprandial glucose, insulin and FGF21 concentrations during the OGTT were lower in active than in sedentary participants. In the older group, only postprandial insulin and FGF21 concentrations were lower in active participants. CONCLUSIONS: FGF21, but not adiponectin, response during the OGTT is higher in older than younger adults and lower in active than sedentary individuals. Exercise-associated reduction in OGTT glucose concentrations was observed in younger but not older adults.

Concentrations of Polybrominated Diphenyl Ethers in Maternal Blood, Placental Size, and Risk for Fetal Growth Restriction: A Nested Case-control Study / 生物医学与环境科学（英文）

Objective@#To explore the effects of prenatal exposure to polybrominated diphenyl ethers (PBDEs) on placental size and birth outcomes.@*Methods@#Based on the perspective Wenzhou Birth Cohort, this nested case-control study included 101 fetal growth restriction (FGR) and 101 healthy newborns. Maternal serum samples were collected during the third trimester and measured for PBDEs by gas chromatography tandem mass spectrometry. The basic information of mother-newborn pairs was collected from questionnaires, whereas the placental size and birth outcomes of newborns were obtained from hospital records.@*Results@#A total of 19 brominated diphenyle ether (BDE) congeners were detected in maternal serum samples. Higher concentrations of BDE-207, -208, -209, and ∑ @*Conclusion@#A negative association was found between PBDE levels in maternal serum and placental size and birth outcomes. Prenatal PBDE exposure may be associated with elevated risk of the incidence of FGR birth.

Heterogeneity of HIV-1 latent reservoirs / 中华医学杂志(英文版)

Antiretroviral therapy (ART) can effectively inhibit human immunodeficiency virus-1 (HIV-1) replication, but is not curative due to the existence of a stable viral latent reservoir harboring replication-competent proviruses. In order to reduce or eliminate the HIV-1 latent reservoir, characteristics of the latently infected cells need to be intensively studied, and a comprehensive understanding of the heterogenous nature of the latent reservoir will be critical to develop novel therapeutic strategies. Here, we discuss the different cell types and mechanisms contributing to the complexity and heterogeneity of HIV-1 latent reservoirs, and summarize the key challenges to the development of cure strategies for acquired immunodeficiency syndrome (AIDS).

Airway microbiome composition correlates with lung function and arterial stiffness in an age-dependent manner.

OBJECTIVE: To investigate age-associated changes in airway microbiome composition and their relationships with lung function and arterial stiffness among genetically matched young and elderly pairs. METHODS: Twenty-four genetically linked family pairs comprised of younger (≤40 years) and older (≥60 years) healthy participants were recruited (Total n = 48). Lung function and arterial stiffness (carotid-femoral pulse wave velocity (PWV) and augmentation index (AIx)) were assessed. Sputum samples were collected for targeted 16S rRNA gene amplicon sequencing and correlations between microbiome composition, lung function and arterial stiffness were investigated. RESULTS: Elderly participants exhibited reductions in lung function (FEV1 (p<0.001), FVC (p<0.001) and percentage FEV1/FVC (p = 0.003)) and a 1.3-3.9-fold increase in arterial stiffness (p<0.001) relative to genetically related younger adults. Elderly adults had a higher relative abundance of Firmicutes (p = 0.035) and lower relative abundance of Proteobacteria (p = 0.014), including specific genera Haemophilus (p = 0.024) and Lautropia (p = 0.020) which were enriched in the younger adults. Alpha diversity was comparable between young and elderly pairs (p>0.05) but was inversely associated with lung function (FEV1%Predicted and FVC %Predicted) in the young (p = 0.006 and p = 0.003) though not the elderly (p = 0.481 and p = 0.696). Conversely, alpha diversity was negatively associated with PWV in the elderly (p = 0.01) but not the young (p = 0.569). Specifically, phylum Firmicutes including the genus Gemella were correlated with lung function (FVC %Predicted) in the young group (p = 0.047 and p = 0.040), while Fusobacteria and Leptotrichia were associated with arterial stiffness (PWV) in the elderly (both p = 0.004). CONCLUSION: Ageing is associated with increased Firmicutes and decreased Proteobacteria representation in the airway microbiome among a healthy Asian cohort. The diversity and composition of the airway microbiome is independently associated with lung function and arterial stiffness in the young and elderly groups respectively. This suggests differential microbial associations with these phenotypes at specific stages of life with potential prognostic implications.

Impact of optional reconstruction kernel on image quality of pulmonary ground glass nodules using the third generation dual-source computed tomography / 中南大学学报(医学版)

To explore the value of the third generation dual-source computed tomography (CT) convolution kernel in display of pulmonary ground-glass nodule (GGN) in transverse image reconstruction.
 Methods: A total of 52 lung adenocarcinoma patients with lung CT data were selected from February 2018 to January 2019 for this study. The pulmonary CT data were reconstructed by convolutional nucleus B157, Br54, and Br49. The signal-to-noise ratio (SNR), the contrast-to-noise ratio (CNR), and the standard deviation (SD) of the image at the GGN were used as the objective evaluation standard of image quality. Subjective image quality was scored by 2 radiologists from 3 aspects (overall image quality, noise, and lesion outline).
 Results: Objective image quality evaluation, SNR and CNR of reconstructed convolution kernel Br49 (SNR: 11.36±5.39, CNR: 7.19±4.29), Br54 (SNR: 8.30±3.35, CNR: 5.09±2.86) are greater than those of Bl57 (SNR: 4.18±2.10, CNR: 3.25±1.78; all P<0.01). SD of reconstructed convolution kernel Br49 (61.80±20.17) and Br54 (80.45±20.31) is smaller than that of Bl57 (137.92±31.11, both P<0.01). In the subjective image quality evaluation, the overall image quality score 5.0(4.5, 5.0) of Br54 was higher than that of all other images [Br49: 3.0(3.0, 4.0), Bl57: 3.0(3.0, 3.5); both P<0.05]. The Br54 image showed that the lesion contour ability score 5.0(4.0, 5.0) was higher than all other images [Br49: 4.0(4.0, 5.0), Bl57: 3.0(3.0, 3.0); both P<0.05]; Br49 image noise score 3.0(3.0, 3.0) is the lowest one [Br54 4.0(4.0, 4.0), Bl57 5.0(5.0, 5.0); both P<0.05].
 Conclusion: The reasonable selection of CT convolution kernel plays an important role in the subjective and objective image quality of GGN. It is suggested that Br54 should be used as the reconstruction of convolutional kernel in pulmonary ground glass nodules, which is helpful for doctors to find and diagnose GGN.

Expression, purification and characterization of recombinant PLCζ protein in baculovirus-insect cell expression system / 生物工程学报

PLCζ is a new isoenzyme of the PLC family which plays an important role in activating mammalian oocytes. In recent years, large-scale expression and purification of active PLCζ protein in vitro for structural biology research has not been successful. In this study, the recombinant human PLCζ protein was expressed and purified in the baculovirus expression system. First, the full length of human PLCζ gene was cloned into the pFastBac-HTA plasmid to form the recombinant donor plasmid that was further transformed into DH10Bac Escherichia coli cells to construct the recombined bacmid by the site-specific transposition that was screened by resistance and blue-white spots. Then the bacmid was transfected to Sf9 insect cells via cellfectin to package the recombinant baculovirus. After the amplification of the recombinant baculovirous, the recombinant protein was expressed from the cells transduced by the recombinant baculovirus and was purified by Ni-NTA resin. Purified protein was identified by Western blotting and time-of-flight mass spectrometry and the enzyme activity was determined. The results showed that the recombinant PLCζ protein in the Sf9 cells was achieved at 72 hours after baculovirus infection and expressed in secreted form in cell culture medium. The recombinant protein purified by Ni²⁺ affinity column was identified as PLCζ by Western blotting and ionization time-of-flight mass spectrometry and the enzyme activity was up to 326.8 U/mL. The experimental results provide a reference for the large-scale production and biological application of recombinant human PLCζ protein.

Analysis of Influential Factors for Drug-induced Liver Injury Caused by Routine Lung Cancer Chemotherapy Plan and Ra- tionality Evaluation of Hepatoprotective Drugs in Our Hospital / 中国药房

OBJECTIVE： To evaluate the influential factors for drug-induced liver injury （DILI） caused by routine lung cancer chemotherapy plan and the rationality of hepatoprotective drugs. METHODS： The information of lung cancer patients receiving routine chemotherapy in our hospital from Feb. 1st， 2018 to Jan. 31st， 2019 were selected. The occurrence of DILI induced by different routine chemotherapy plans， the correlation of each influential factor with DILI and the rationality of hepatoprotective drugs were analyzed retrospectively. RESULTS： A total of 325 patients were involved in this study， among which 126 patients （38.77％） suffered from DILI， involving 109 first-level cases （33.54％） and 17 second-level cases （5.23％）. Routine chemotherapy plan included etoposide+cisplatin， gemcitabine+cisplatin， docetaxel+platinum， pemetrexed disodium+platinum. The clinical classification of DILI included hepatocyte injury type 44 cases （14.52％）， cholestasis type 38 cases （12.54％） and mixed type 37 cases （12.21％）. Totally 174 patients （53.54％） received hepatoprotective drugs during chemo-therapy， among whom 49 patients （28.16％） suffered from first-level DILI and 6 patients （3.45％） second-level DILI， with total incidence of 31.61％. Among patients without hepatoprotective drugs， 60 patients （39.74％） suffered from first-level DILI， and 11 patients （7.28％） suffered from second-level DILI， with total incidence of 47.02％. The incidence of DILI in patients without hepatoprotective drugs was significantly higher than those with hepatoprotective drugs （P＜0.05）. Among patients with hepatoprotective drugs， 23 patients （13.22％） used hepatoprotective drugs unreasonably， including 5 patients （2.87％） received 3 kinds or more hepatoprotective drugs； 3 patients （1.72％） received drugs with same mechanism repeatedly； 11 patients （6.32％） received 3 kinds or more drugs and drug with same mechanism repeatedly； 4 patients （2.30％） used drugs contrary to contraindication. Influential factor correlation analysis showed that there was a positive correlation between DILI and the dosage of chemotherapeutic drugs， treatment course and KPS before chemotherapy （P＜0.05）. CONCLUSIONS： KPS before chemotherapy， dosage of chemotherapeutic agents and treatment course are the main factors of DILI. There is still unreasonable use of drugs such as repeated use， unreasonable drug combination， violation of drug contraindications. The use of hepatoprotective drugs during chemotherapy can reduce the risk of DILI occurrence. Clinicians should be more aware of the methods and indications of hepatoprotective drugs in order to improve the effectiveness and safety of drug use.

Clinical value of IL-6 combined with CA125 and HE4 in the diagnosis of early ovarian cancer / 国际检验医学杂志

Objective To discuss the clinical value of IL-6 combined with CA125 and HE4 as a new association marker in the diagnosis of early ovarian cancer.Methods The expression of IL-6, CA125 and HE4 in 21 cases of early ovarian cancer (stageⅠ-Ⅱ), 36 cases of advanced ovarian cancer (stageⅢ-Ⅳ), 40 cases of benign ovarian tumor and 40 healthy women were measured by the Roche automatic chemiluminescence analyzer (electrochemiluminescence).The sensitⅣity, specificity, positive predictive value, negative predictive value and ROC curves were used to evaluate the diagnostic value.Results The serum levels of IL-6, CA125 and HE4 in patients with ovarian cancer were significantly higher than those in the benign ovarian tumor and the healthy control (P＜0.05).The sensitⅣity, specificity, positive predictive value and negative predictive value of IL-6 combined with CA125 and HE4 were respectively 85.7％, 90％, 81.8％, 92.3％in the diagnosis of early ovarian cancer (stageⅠ-Ⅱ) patients and respectively 94.4％, 97.5％, 97.1％and 95.1％for advanced ovarian cancer (stageⅢ-Ⅳ) patients.For IL-6 combined with CA125 and HE4, the ROC AUC was respectively 0.955 4 and 0.974 0 for early ovarian cancer (stageⅠ-Ⅱ) patients and advanced ovarian cancer (stageⅢ-Ⅳ) patients.It performed significantly better than any single test of IL-6, CA125 and HE4 and the 2-marker combination of CA125+HE4.Conclusion The marker panel, IL-6, CA125 and HE4, shows higher sensitⅣity, positive predictive value and ROC AUC.It is an ideal serum marker combination for the diagnosis of early ovarian cancer (stageⅠ-Ⅱ) patients, which can improve the diagnostic efficiency of early ovarian cancer.

One-stage repair of ankle fracture combined with grade Ⅲ injury to lateral ligament / 中华创伤骨科杂志

Objective To investigate the surgical outcomes of one-stage repair of the ankle fracture combined with grade Ⅲ injury to the lateral ligament.Methods From April 2015 to December 2017,23 patients with ankle fracture and lateral ligament injury were treated at Department of Traumatic Reconstruction Surgery/Foot and Ankle Surgery,Zhongnan Hospital.There were 15 males and 8 females,aged from 18 to 65 years (average,37.8 years).After intraoperative treatment of their fractures,22 ruptures of the ligamentous insertion were repaired with suture anchor and one rupture of the middle ligament with Internal Brace.Routine postoperative X-rays,physical examination and Sefton grading system were used to evaluate the stability of the ankle joint and the subtalar joint.The Karlsson-Peterson and American Orthopedic Foot and Ankle Society (AOFAS) scores were used to evaluate the function and pain of the ankle.Results The follow-up for this cohort ranged from 12 to 24 months (average,13.9 months).The bone union time ranged from 6 to 24 weeks,averaging 10.1 weeks.There was no chronic instability of lateral ankle or subtalar joint in all the cases.Two cases developed osteochondral lesion of the medial talus which was treated with micro-fracture surgery one year after injury;one case suffered subtalar arthritis which was treated by subtalar arthrodesis 14 months after injury.Their Karlsson-Peterson scores averaged 84.6 points and AOFAS ankle-hindfoot scores 93.7 points with 19 excellent and 4 good cases.The Sefton grading system gave 9 cases of grade Ⅰ and 14 ones of grade Ⅱ.Conclusion One-stage repair of the ankle fracture combined with grade Ⅲ injury to the lateral ligament can lead to the stability of the ankle joint and the subtalar joint and improved function of the ankle.