The coinfection of respiratory viruses and bacteria is a major cause of morbidity and mortality worldwide, despite the development of vaccines and powerful antibiotics. As a macromolecule that is difficult to absorb in the gastrointestinal tract, a homogeneous polysaccharide from Houttuynia cordata (HCPM) has been reported to exhibit anti-complement properties and alleviate influenza A virus (H1N1)-induced lung injury; however, the effects of HCPM without in vitro antiviral and antibacterial activities on more complicated pulmonary diseases resulting from viral-bacterial coinfection remains unclear. This study established a representative coinfection murine pneumonia model infected with H1N1 (0.2 LD₅₀) and methicillin-resistant Staphylococcus aureus (MRSA, 10⁷ CFU). HCPM significantly improved survival rate and weight loss, and ameliorated gut-lung damage and inflammatory cytokine production. Interestingly, the therapeutic effect of HCPM on intestinal damage preceded that in the lungs. Mechanistically, HCPM inhibited the overactivation of the intestinal complement (C3a and C5a) and suppressed the activation of the NLR family pyrin domain-containing 3 (NLRP3) pathway, which contributes to the regulation of the Treg/Th17 cell balance in the gut-lung axis. The results indicate the beneficial effects of an anti-complement polysaccharide against viral-bacterial coinfection pneumonia by modulating crosstalk between multiple immune regulatory networks.

BACKGROUND:At present,there is still controversy in clinical practice about the choice of internal fixation of Pauwels type Ⅲ femoral neck fracture,and the selection of internal fixation that provides stable fixation strength is the key basis for achieving Pauwels type Ⅲ fracture fixation. OBJECTIVE:The three-dimensional finite element analysis method was used to test the difference in biomechanical strength of three types of internal fixation in Pauwels type Ⅲ femoral neck fracture,which provided a reference for its clinical treatment. METHODS:Using the CT data of the left femur of a healthy male volunteer,a complete femur and its cancellous bone were reconstructed in Mimics software,and Geomagic studio software was used for reverse modeling.Cannulated compression screw,dynamic hip screw,and femoral neck system were created in UG-NX software.Three kinds of internal fixation models were assembled on the femur model,and Pauwels type Ⅲ femoral neck fracture was simulated by Hypermesh software.Finally,Abaqus software was used to carry out finite element experimental analysis to analyze and compare the stress distribution,stress peak,strain,and displacement distribution caused by fixed femoral neck fracture of different internal fixation systems. RESULTS AND CONCLUSION:(1)The stress of the proximal femur bone mass was mainly distributed in the area below the femoral neck near the fracture end,with the highest stress peak in the dynamic hip screw group and the smallest in the femoral neck system group.(2)The stress distribution of the internal fixation device was mainly concentrated on the screw surface near the fracture line,with the highest stress peak in the femoral neck system group and the smallest in the dynamic hip screw group.(3)The main strain field of the proximal femur bone mass was distributed in the upper surface area where the bone and screw contacted,and the yield strain was the smallest in the femoral neck system group and the largest in the cannulated compression screw group.(4)The main strain field of the internal fixation device model was distributed on the upper surface of the femoral neck screw,with the yield strain being the smallest in the femoral neck system group and the largest in the cannulated compression screw group.(5)The displacement distribution values of femur,proximal bone mass,distal bone block,internal fixation device and internal fixation with the femur as a whole in the three femoral neck fracture internal fixation models decreased gradually from proximal to distal,and the peak displacement of the femoral neck system group was the largest and the lowest in the dynamic hip screw group.(6)The results showed that when the Pauwels type Ⅲ femoral neck fracture was fixed,the stress distribution of femoral neck system was more uniform,the mechanical conduction characteristics were better,and it was subjected to lower yield strain,higher stress and higher displacement.It has relatively better biomechanical stability and can provide a superior mechanical environment for fracture healing.

Assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) is a technique widely used to investigate genome-wide chromatin accessibility. The recently published Omni-ATAC-seq protocol substantially improves the signal/noise ratio and reduces the input cell number. High-quality data are critical to ensure accurate analysis. Several tools have been developed for assessing sequencing quality and insertion size distribution for ATAC-seq data;however, key quality control (QC) metrics have not yet been established to accurately determine the quality of ATAC-seq data. Here, we optimized the analysis strategy for ATAC-seq and defined a series of QC metrics for ATAC-seq data, including reads under peak ratio (RUPr), background (BG), promoter enrichment (ProEn), subsampling enrichment (SubEn), and other measurements. We incorporated these QC tests into our recently developed ATAC-seq Integrative Analysis Package (AIAP) to provide a complete ATAC-seq analysis system, including quality assurance, improved peak calling, and downstream differential analysis. We demonstrated a significant improvement of sensitivity (20％–60％) in both peak calling and differential analysis by processing paired-end ATAC-seq datasets using AIAP. AIAP is compiled into Docker/Singularity, and it can be executed by one command line to generate a comprehensive QC report. We used ENCODE ATAC-seq data to benchmark and generate QC recommendations, and developed qATACViewer for the user-friendly interaction with the QC report. The software, source code, and documentation of AIAP are freely available at https://github.com/Zhang-lab/ATAC-seq_QC_analysis.

Objective:To explore the effect of neurolysis and tendon transplantation in functional reconstruction of the upper limb with severe thermal crush injury.Methods:A retrospective case series study was conducted to analyze the clinical data of 12 patients with thermal crush injuries of the upper limb admitted to Changhai Hospital of Naval Medical University from January 2014 to December 2018. There were 9 males and 3 females, aged 22-54 years (mean, 38 years). The percentage of total body surface area (TBSA) burn ranged from 3% to 8% [(4.9±1.4)%], and wound depth was III degree. According to the damage condition of nerve/tendon and whether there was any dysfunction of the affected limb after wound healing, 12 patients received 2 to 4 times of neurolysis and tendon transplant-related surgeries, with an average surgery of 2.7 times. Among them, a total of 18 times of neurolysis were performed, including 7 times of radial neurolysis, 6 times of median nerve neurolysis and 5 times of ulnar neurolysis, and 14 times of tendon transplantation were done, including 6 times of anastomosis of superficial flexor tendon and long thumb extensor tendon, 5 times of tendon repair transplantation and 3 times of anastomosis of lateral wrist extensor tendon and long thumb extensor tendon. The time interval of each operation was 3-6 months [(4.5±1.0) months]. The Changhai pain ruler, disability of arm-shoulder-hand table (DASH) and joint activity assessment table were assessed before the first operation, 3 months and 6 months after the last operation.Results:All the patients were followed up for 6-12 months (mean, 9.2 months). The score of Changhai pain ruler in the affected limb improved from 3 (2, 3)points before surgery to 1 (0.5, 1)points 3 months after surgery and 1 (0, 1)points 6 months after surgery ( P<0.01). The score of DASH improved from (69.9±2.7) points before surgery to (35.1±1.7) points 3 months after surgery and (33.8±2.0) points 6 months after surgery ( P<0.01). The range of motion score was improved from (1.3±0.5) points before surgery to (2.4±0.5) points 3 months after surgery and (2.8±0.4) points 6 months after surgery ( P<0.01). Conclusion:Neurolysis and tendon transplantation in the treatment of severe thermal crush injuries of the upper limb can alleviate pain in the affected limbs, improve upper limb dysfunction, increase mobility of the palm and upper limb joints, and enhance the quality of life of the patients.

Objective Thresholds for auditory brain stem responses (ABRs) to tone burst and tone burst in notched noises of two different intensities were tested in adults with sensorineural hearing loss.The relationship between ABR and puretone thresholds was analyzed to identify an acoustic stimuli with better frequency-specificity.Methods Thirty-eight adults with sensorineural hearing loss (totally 45 ears) were included in the study.Tone burst used to elicit ABRs had 2.5 cycles on the rise and fall and no plateau.Notched noises of two different intensities were used to mask tone burst ipsilaterally when recording ABRs.Those two kinds of notched noises were 25 dB (intensity A) and 15 dB (intensity B) lower than tone burst in intensity respectively.Tone burst ABRs without masking were named tb-ABR,while tone burst ABRs in notched noises of intensity A and B named as amtb-ABR and bmtb-ABR.Thresholds for tb ABR,amtb ABR and bmtb-ABR were tested and analyzed.Results The regression coefficients between puretone thresholds and thresholds for tb-ABR,amtb-ABR and bmtb-ABR of all frequencies were greater than 0.8.The mean differences between ABR and puretone thresholds were all less than 10 dB.Tb-ABR thresholds the were the closest to puretone thresholds at 500 Hz,while bmtb ABR thresholds were the closest at the other three frequencies.Bmtb-ABR thresholds were more close to puretone thresholds in patients with steeply sloping hearing loss.Conclusion Thresholds for all those three ABRs could be used to predict puretone thresholds.In most condition,tb-ABR thresholds were able to estimate puretone thresholds.In some condition,different stimuli could be chosen to elicit ABR at different frequencies.It was reasonable to choose bmtb -ABR for puretone thresholds estimation in patients with steeply sloping hearing loss.

Thunb. is a traditional herb used for clearing heat and eliminating toxins, and has also been used for the treatment of severe acute respiratory syndrome (SARS). the crude polysaccharides (CHCP) exhibited potent anti-complementary activity through both the classical and alternative pathways by acting on components C3 and C4 of the complement system without interfering with the coagulation system. This study was to investigate the preventive effects of CHCP on acute lung injury (ALI) induced by hemorrhagic shock plus lipopolysaccharide (LPS) instillation (two-hit) and LPS-induced fever in rats. CHCP significantly attenuated pulmonary injury in the "two-hit" ALI model by reducing pulmonary edema and protein exudation in bronchoalveolar lavage fluid (BALF). In addition, it reduced the deposit of complement activation products in the lung and improved oxidant-antioxidant imbalance. Moreover, CHCP administration inhibited fever in rats, reduced the number of leukocytes and restored serum complement levels. The inhibition on the inappropriate activation of complement system by CHCP may play an important role in its beneficial effects on inflammatory diseases. The anti-complementary polysaccharides are likely to be among the key substances for the heat-clearing function of .

Objective To compare the results of TEOAE and DPOAE in the same population of normal newborns, to provide information on choosing appropriate screening tools.Methods A two-steps protocol was taken with the first screening during the first 48 to 72 hours of birth and rescreened from one to two months old if the newborns failed the first screening.For each step of screening, TEOAE and DPOAE were performed simultaneously using AccuScreen hearing screening instrument (Madsen-GN Otometrics, Taastrup, Denmark).A total of 1 062 normal newborns (F/M=508/554) delivered in Peking Union Medical College Hospital were enrolled in this research for the first screening.Infants who failed either TEOAE or DPOAE screening in the first screening were referred to a second screening.Among them, 135 performed both DPOAE and TEOAE in the second step.The newborns who failed the second screening would receive ABR when they were 3 months old.Results In the first screening,the failure rate for TEOAE was 11.0% (117/1 062) and 13.7% (145/1 062) for DPOAE.In the second screening step, the failure rates were 17.8% (24/135) and 20.7% (28/135) for TEOAE and DPOAE, respectively.Chi-square and Fisher's test showed that the failure rates of DPOAE were significant higher than TEOAE for both steps (P<0.001).The agreements between TEOAE and DPOAE were 96.0% and 95.6% for the first and second steps respectively, and the kappa values were 0.817 and 0.857.As to the average time taken to accomplish the screening for one ear, TEOAE was 24±25 s and DPOAE was 40±34 s during the first screening;in the rescreening, TEOAE was 52±41 s and DPOAE was 73±62 s.Paired-t tests showed that the differences between DPOAE and TEOAE testing time were statistically significant (P=0.000) in both screening steps.Finally, 7 newborns (10 ears) were diagnosed conductive hearing loss(except 1 ear was sensorineural hearing loss).Conclusion As a screening tool, TEOAE got lower refer rates and took less time than DPOAE implicating TEOAE a better screening tool for normal neonates.

Objective To determine the influences of quality control method of process decision program chart ( PDPC ) on preventing complications related to indwelling catheter in female patients with neurogenic urinary incontinence after stroke. Methods We selected 94 female patients with neurogenic urinary incontinence after the first stroke. A total of 48 patients without accepting PDPC interventions from January 2014 to January 2015 were selected as control group. A total of 46 patients accepting systematic PDPC interventions from February 2015 to January 2016 were selected as intervention group. Patients in control group were provided with nursing care based on the nursing requirements of the indwelling catheter in Basic Nursing Science. Patients in intervention group were provided with nursing care according to the process of PDPC. And then, we compared the catheter related complications of patients between two groups and the self-evaluation of nurses. Results The incidence of complications including urinary tract infection and urethral injury in intervention group was lower than that in control group with a significant difference ( P<0.05) . After the PDPC method was carried out, the self-evaluation involving responsibility, work enthusiasm, and self-confidence of nurses was significantly improved. Conclusions The application of PDPC in female patients with neurogenic urinary incontinence and indwelling catheter after stroke not only can reduce the incidence of complications, effectively improve nursing quality, but also can expand nurses′ thinking, hoisting their abilities to solve problems and improve their self-evaluations.

Traditionally, determination of inhibitory potency of complement inhibitors is performed by the hemolytic assay. However, this assay is not applicable to the lectin pathway, thus impeding the understanding of complement inhibitors against the overall function of the complement system. The main objective of our study was to develop a specific enzyme-linked immunosorbent assay (ELISA) as an alternative method to assess the anti-complement activity, particularly against the lectin pathway. By using respective coating substrates against different activation pathways, followed by capturing the stable C3c fragments, our ELISA method can be used to screen complement inhibitors against the classical pathway and the lectin pathway. The inhibitory effect of suramin on the classical pathway, as measured by our hemolytic assay is consistent with previous reports. Further assessment of suramin and Bupleurum polysaccharides against the lectin pathway showed a good reproducibility of the method. Comparison of the lectin pathway IC50 between Bupleurum smithii var. parvifolium polysaccharides (1.055 mg/mL) and Bupleurum chinense polysaccharides (0.98 mg/mL) showed that, similar to the classical and alterative pathway, these two Bupleurum polysaccharides had comparable anti-complementary properties against the lectin pathway. The results demonstrate that the described ELISA assay can compensate for the shortcomings of the hemolytic assay in lectin pathway.

PURPOSE: Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) are an inhibitor of receptor tyrosine kinases (RTKs) that was discovered in recent years, and many studies showed that LRIG1 is a tumor suppressor gene and may be related to tumor drug resistance. In this study, we explored whether LRIG1 protein expression can improve the chemosensitivity of glioma cells and what was its mechanism. MATERIALS AND METHODS: We collected 93 cases of glioma tissues and detected the expression of LRIG1 and BCL-2. We constructed a multidrug resistance cell line U251/multidrug resistance (MDR) and examined the change of LRIG1 and BCL-2 at mRNA and protein expression levels. LRIG1 expression was upregulated in U251/MDR cells and we detected the change of multidrug resistance. Meanwhile, we changed the expression of LRIG1 and BCL-2 and explored the relationship between LRIG1 and BCL-2. Finally, we also explored the relationship between LRIG1 and RTKs. RESULTS: LRIG1 was negatively correlated with BCL-2 expression in glioma tissue and U251/MDR cells, and upregulation of LRIG1 can enhance chemosensitivity and inhibit BCL-2 expression. Furthermore, LRIG1 was negatively correlated with RTKs in U251/MDR cells. CONCLUSION: These results demonstrated that LRIG1 can improve chemosensitivity by modulating BCL-2 expression and RTK signaling in glioma cells.
Astrocytoma/drug therapy/genetics/metabolism ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics/*physiology ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Glioma/drug therapy/*metabolism ; Humans ; Membrane Glycoproteins/metabolism/*physiology ; Proto-Oncogene Proteins c-bcl-2/*metabolism ; RNA, Messenger/metabolism ; Receptor Protein-Tyrosine Kinases/metabolism