Low-frequency rTMS targeting individual self-initiated finger-tapping task activation modulates the amplitude of local neural activity in the putamen.

Repetitive transcranial magnetic stimulation (rTMS) has been used in the clinical treatment of Parkinson's disease (PD). Most of rTMS studies on PD used high-frequency stimulation; however, excessive nonvoluntary movement may represent abnormally cortical excitability, which is likely to be suppressed by low-frequency rTMS. Decreased neural activity in the basal ganglia on functional magnetic resonance imaging (fMRI) is a characteristic of PD. In the present study, we found that low-frequency (1 Hz) rTMS targeting individual finger-tapping activation elevated the amplitude of local neural activity (percentage amplitude fluctuation, PerAF) in the putamen as well as the functional connectivity (FC) of the stimulation target and basal ganglia in healthy participants. These results provide evidence for our hypothesis that low-frequency rTMS over the individual task activation site can modulate deep brain functions, and that FC might serve as a bridge transmitting the impact of rTMS to the deep brain regions. It suggested that a precisely localized individual task activation site can act as a target for low-frequency rTMS when it is used as a therapeutic tool for PD.

Higher reliability and validity of Wavelet-ALFF of resting-state fMRI: From multicenter database and application to rTMS modulation.

Amplitude of low-frequency fluctuation (ALFF) has been widely used for localization of abnormal activity at the single-voxel level in resting-state fMRI (RS-fMRI) studies. However, previous ALFF studies were based on fast Fourier transform (FFT-ALFF). Our recent study found that ALFF based on wavelet transform (Wavelet-ALFF) showed better sensitivity and reproducibility than FFT-ALFF. The current study aimed to test the reliability and validity of Wavelet-ALFF, and apply Wavelet-ALFF to investigate the modulation effect of repetitive transcranial magnetic stimulation (rTMS). The reliability and validity were assessed on multicenter RS-fMRI datasets under eyes closed (EC) and eyes open (EO) conditions (248 healthy participants in total). We then detected the sensitivity of Wavelet-ALFF using a rTMS modulation dataset (24 healthy participants). For each dataset, Wavelet-ALFF based on five mother wavelets (i.e., db2, bior4.4, morl, meyr and sym3) and FFT-ALFF were calculated in the conventional band and five frequency sub-bands. The results showed that the reliability of both inter-scanner and intra-scanner was higher with Wavelet-ALFF than with FFT-ALFF across multiple frequency bands, especially db2-ALFF in the higher frequency band slow-2 (0.1992-0.25 Hz). In terms of validity, the multicenter ECEO datasets showed that the effect sizes of Wavelet-ALFF with all mother wavelets (especially for db2-ALFF) were larger than those of FFT-ALFF across multiple frequency bands. Furthermore, Wavelet-ALFF detected a larger modulation effect than FFT-ALFF. Collectively, Wavelet db2-ALFF showed the best reliability and validity, suggesting that db2-ALFF may offer a powerful metric for inspecting regional spontaneous brain activities in future studies.

De novo disruptive heterozygous MMP21 variants are potential predisposing genetic risk factors in Chinese Han heterotaxy children.

BACKGROUND: Heterotaxy syndrome (HTX) is caused by aberrant left-right patterning early in embryonic development, which results in abnormal positioning and morphology of the thoracic and abdominal organs. Currently, genetic testing discerns the underlying genetic cause in less than 20% of sporadic HTX cases, indicating that genetic pathogenesis remains poorly understood. In this study, we aim to garner a deeper understanding of the genetic factors of this disease by documenting the effect of different matrix metalloproteinase 21 (MMP21) variants on disease occurrence and pathogenesis. METHODS: Eighty-one HTX patients with complex congenital heart defects and 89 healthy children were enrolled, and we investigated the pathogenetic variants related to patients with HTX by exome sequencing. Zebrafish splice-blocking Morpholino oligo-mediated transient suppression assays were performed to confirm the potential pathogenicity of missense variants found in these patients with HTX. RESULTS: Three MMP21 heterozygous non-synonymous variants (c.731G > A (p.G244E), c.829C > T (p.L277F), and c.1459A > G (p.K487E)) were identified in three unrelated Chinese Han patients with HTX and complex congenital heart defects. Sanger sequencing confirmed that all variants were de novo. Cell transfection assay showed that none of the variants affect mRNA and protein expression levels of MMP21. Knockdown expression of mmp21 by splice-blocking Morpholino oligo in zebrafish embryos revealed a heart looping disorder, and mutant human MMP21 mRNA (c.731G > A, c.1459A > G, heterozygous mRNA (wild-type&c.731G > A), as well as heterozygous mRNA (wild-type& c.1459A > G) could not effectively rescue the heart looping defects. A patient with the MMP21 p.G244E variant was identified with other potential HTX-causing missense mutations, whereas the patient with the MMP21 p.K487E variant had no genetic mutations in other causative genes related to HTX. CONCLUSION: Our study highlights the role of the disruptive heterozygous MMP21 variant (p.K487E) in the etiology of HTX with complex cardiac malformations and expands the current mutation spectrum of MMP21 in HTX.

Resting-State fMRI Functional Connectivity Strength Predicts Local Activity Change in the Dorsal Cingulate Cortex: A Multi-Target Focused rTMS Study.

Previous resting state functional magnetic resonance imaging (RS-fMRI) studies suggested that repetitive transcranial magnetic stimulation (rTMS) can modulate local activity in distant areas via functional connectivity (FC). A brain region has more than one connection with the superficial cortical areas. The current study proposed a multi-target focused rTMS protocol for indirectly stimulating a deep region, and to investigate 1) whether FC strength between stimulation targets (right middle frontal gyrus [rMFG] and right inferior parietal lobule [rIPL]) and effective region (dorsal anterior cingulate cortex [dACC]) can predict local activity changes of dACC and 2) whether multiple stimulation targets can focus on the dACC via FC. A total of 24 healthy participants received rTMS with two stimulation targets, both showing strong FC with the dACC. There were four rTMS conditions (>1 week apart, 10 Hz, 1800 pulses for each): rMFG-target, rIPL-target, Double-targets (900 pulses for each target), and Sham. The results failed to validate the multi-target focused rTMS hypothesis. But rMFG-target significantly decreased the local activity in the dACC. In addition, stronger dACC-rMFG FC was associated with a greater local activity change in the dACC. Future studies should use stronger FC to focus stimulation effects on the deep region.

VARAdb: a comprehensive variation annotation database for human.

With the study of human diseases and biological processes increasing, a large number of non-coding variants have been identified and facilitated. The rapid accumulation of genetic and epigenomic information has resulted in an urgent need to collect and process data to explore the regulation of non-coding variants. Here, we developed a comprehensive variation annotation database for human (VARAdb, http://www.licpathway.net/VARAdb/), which specifically considers non-coding variants. VARAdb provides annotation information for 577,283,813 variations and novel variants, prioritizes variations based on scores using nine annotation categories, and supports pathway downstream analysis. Importantly, VARAdb integrates a large amount of genetic and epigenomic data into five annotation sections, which include 'Variation information', 'Regulatory information', 'Related genes', 'Chromatin accessibility' and 'Chromatin interaction'. The detailed annotation information consists of motif changes, risk SNPs, LD SNPs, eQTLs, clinical variant-drug-gene pairs, sequence conservation, somatic mutations, enhancers, super enhancers, promoters, transcription factors, chromatin states, histone modifications, chromatin accessibility regions and chromatin interactions. This database is a user-friendly interface to query, browse and visualize variations and related annotation information. VARAdb is a useful resource for selecting potential functional variations and interpreting their effects on human diseases and biological processes.

Reliability and repeatability of 2021 ARCO classification and its guiding significance in treatment of nontraumatic osteonecrosis of the femoral head.

BACKGROUND: The study was designed to evaluate the interobserver reliability and intraobserver repeatability of the 2021 Association Research Circulation Osseous (ARCO) classification and explore its guiding significance in the treatment of nontraumatic osteonecrosis of the femoral head (ONFH). METHODS: In this retrospective study, we randomly selected and investigated 50 sets of preoperative computed tomography or magnetic resonance imaging scans from 96 patients (139 hips) to validate the reliability and repeatability of the 2021 ARCO classification. Patients with a nano-hydroxyapatite/polyamide-66 support rod were included in the clinical efficacy study. The Harris hip score (HHS) was used to assess hip function. Femoral head collapse of > 2 mm was considered radiological failure. Total hip arthroplasty (THA) was performed for clinical failure, and follow-up was discontinued. RESULTS: The average kappa value of interobserver consistency was 0.652. The average rate of consistency was 90.25%, and the average kappa value of intraobserver consistency was 0.836. Eighty-two patients (122 hips) were enrolled and followed up for a mean of 43.57 ± 9.64 months. There was no significant difference in the HHS among the three groups before surgery, but the difference was statistically significant at the last follow-up. Among them, types 1 and 2 had significantly higher scores at the last follow-up than preoperatively (P < 0.05), whereas type 3 had a lower score at the last follow-up than preoperatively, although the difference was not statistically significant (P > 0.05).According to the imaging evaluation, the failure rate of type 1, 2, and 3 at the last follow-up was 0%, 19%, and 87%, respectively. Univariate analysis showed that the femoral head survival rate of radiography was significantly affected by the new classification system (P = 0.00). At the last follow-up, the incidence rate of THA in type 1, 2, and 3 was 5%, 7%, and 31%, respectively. Univariate analysis showed that the femoral head survival rate was significantly affected by the new classification system (P = 0.001). CONCLUSIONS: The 2021 ARCO classification for early-stage ONFH shows substantial consistency and repeatability. We do not recommend femoral head-preserving surgery for patients with type 3 ONFH.

The role of prophylactic antibiotics in elective inguinal tension-free hernia repair: A systematic review and meta-analysis.

Whether to use antibiotics to prevent surgical site infection in elective inguinal tension-free hernia repair has been controversial. To systematically evaluate the effect of prophylactic antibiotic application in elective inguinal tension-free hernia repair, we identified all published randomised controlled trials of the effect of prophylactic antibiotic application on elective inguinal tension-free hernia repair were collected by computer retrieval from the China National Knowledge Infrastructure; VIP Database; Wanfang Database; China Biomedical Literature Database; and PubMed, EMBASE and Cochrane Library databases. Meta-analysis was performed by RevMan 5.3 software. The meta-analysis showed that the total incidence of surgical site infections [P = 0.003] and the incidence of superficial surgical site infections [P = 0.004] in the antibiotic group (AG) were lower than those in the non-antibiotic group (NAG). There was no significant difference in the total incidence of postoperative infections [P = 0.06], deep surgical site infections [P = 0.26] and seroma [P = 0.52] between the AG and the NAG. Based on current evidence, the application of prophylactic antibiotics in elective inguinal tension-free hernia repair can prevent the total incidence of surgical site infections and that of superficial surgical site infections but cannot prevent the total incidence of postoperative infection events, incidence of deep surgical site infections and incidence of seroma.

Evaluation of the diagnostic performance of the EFSUMB CEUS Pancreatic Applications guidelines (2017 version): a retrospective single-center analysis of 455 solid pancreatic masses.

OBJECTIVES: To explore the diagnostic performance of EFSUMB CEUS Pancreatic Applications guidelines (version 2017) before and after the addition of iso-enhancement and very fast/fast washout as supplementary diagnostic criteria for PDAC. METHODS: In this retrospective study, patients diagnosed with solid pancreatic lesions from January 2017 to December 2020 were evaluated. Pancreatic ductal adenocarcinoma (PDAC) is reported to show hypo-enhancement in all phases according to the EFSUMB guidelines. First, based on this definition, all lesions were categorized as PDAC and non-PDAC. Then, iso-enhancement and very fast/fast washout were added as supplementary diagnostic criteria, and all lesions were recategorized. The diagnostic performance was assessed in terms of the accuracy (ACC), sensitivity (SEN), specificity (SPE), positive predictive value (PPV), and negative predictive value (NPV). The reference standard consisted of histologic evaluation or composite imaging and clinical follow-up findings. RESULTS: A total of 455 nodules in 450 patients (median age, 58.37 years; 250 men) were included. The diagnostic performance using the EFSUMB CEUS guidelines for PDAC had an ACC of 69.5%, SEN of 65.4%, SPE of 84%, PPV of 93.5%, NPV of 40.6%, and ROC of 0.747. After recategorization according to the supplementary diagnostic criteria, the diagnostic performance for PDAC had an ACC of 95.8%, SEN of 99.2%, SPE of 84%, PPV of 95.7%, NPV of 96.6%, and ROC of 0.916. CONCLUSION: The EFSUMB guidelines and recommendations for pancreatic lesions can effectively identify PDAC via hypo-enhancement on CEUS. However, the diagnostic performance may be further improved by the reclassification of PDAC lesions after adding iso-enhancement and very fast/fast washout mode. KEY POINTS: • In the EFSUMB guidelines, the only diagnostic criterion for PDAC is hypo-enhancement, to which iso-enhancement and very fast/fast washout mode were added in our research. • Using hypo-enhancement/iso-enhancement with very fast/fast washout patterns as the diagnostic criteria for PDAC for solid pancreatic masses on CEUS has high diagnostic accuracy. • The blood supply pattern of PDAC can provide important information, and CEUS has unique advantages in this respect due to its real-time dynamic attenuation ability.

HSF-1 mediated combined ginsenosides ameliorating Alzheimer's disease like symptoms in Caernorhabditis elegans.

There are few effective medications to treat Alzheimer's disease (AD). It has been suggested that several ginsenosides possess mild or moderate anti-AD activity. In our present work, a preferred combined ginsenosides was shown to have a more significant benefit effect on AD-like symptoms of worm paralysis and hypersensitivity to exogenous 5-HT in C. elegans. The combined ginsenosides can suppress Aß deposits and Aß oligomers, alleviating the toxicity induced by Aß overexpression more effectively than used alone. Its anti-AD effect was partially abolished by hsf-1 RNAi knocked down or hsf-1 inactivation by point mutation, but not by daf-16 or skn-1 RNAi knocked down. Furthermore, it markedly activated hsp-16.2 gene expression downstream of HSF-1. Our results demonstrated that HSF-1 signaling pathway exerts an important role in mediating the therapeutic effect of combined ginsenosides on AD worms. These results provided powerful evidences and theoretical foundation for reshaping medicinal products of ginsenosides and ginseng on prevention of neurodegenerative diseases.

Light-triggered multifunctional nanoplatform for efficient cancer photo-immunotherapy.

Cancer immunotherapy is limited by the immune escape of tumor cells and adverse effects. Photo-immunotherapy, the combination of immunotherapy and phototherapy (such as photodynamic therapy (PDT) and photothermal therapy (PTT)), can improve the effectiveness of immunotherapy in cancer treatment. Here, we first explored mesoporous hexagonal core-shell zinc porphyrin-silica nanoparticles (MPSNs), which are composed of a zinc porphyrin core and a mesoporous silica shell, and exhibit high laser-triggered photodynamic and photothermal activity, as well as outstanding drug loading capacity. In other words, MPSNs can be used not only as excellent photosensitizers for photo-immunotherapy, but also as an ideal drug carrier to achieve more efficient synergy. After loading with R837 (imiquimod, a toll-like receptor-7 agonist), MPSNs@R837 will elicit high-efficiency immunogenic cell death via PDT and PTT, and promote dendritic cell maturation after the PH-responsive release of R837, thereby, inducing tumor-specific immune responses. When combined with a programmed death ligand-1 checkpoint blockade, the photo-immunotherapy system markedly restrains primary tumors and metastatic tumors with negligible systemic toxicity. Therefore, the therapeutic strategy of integrating PTT, PDT and checkpoint blockade, shows great potential for suppressing cancer metastasis.

Preliminary report of the outcomes and indications of single approach, double-channel core decompression with structural bone support and bone grafting for osteonecrosis of the femoral head.

BACKGROUND: To report the outcomes of the single approach to double-channel core decompression and bone grafting with structural bone support (SDBS) for osteonecrosis of the femoral head (ONFH) and define the indications. METHODS: One-hundred-and-thirty-nine hips in 96 patients (79 males, 17 females; mean age 37.53±10.31 years, range 14-58 years; mean body mass index 25.15±3.63 kg/m2) were retrospectively analysed. The Harris hip score (HHS) was used to assess hip function, and radiographs were used to assess the depth of femoral head collapse. Treatment failure was defined as the performance of total hip arthroplasty (THA). The variables assessed as potential risk factors for surgical failure were: aetiology, Japanese Osteonecrosis Investigation Committee (JIC) type, age, and Association Research Circulation Osseous (ARCO) stage. Complications were recorded. RESULTS: The mean follow-up time was 29.26±10.02 months. The HHS increased from 79.00±13.61 preoperatively to 82.01±17.29 at final follow-up (P=0.041). The average HHS improvement was 3.00±21.86. The combined excellent and good rate at final follow-up (65.6%) was significantly higher than that before surgery (34.5%) (P<0.05). On radiographic evaluation, 103 (74.1%) hips remained stable, while 36 (25.9%) had femoral head collapse or aggravation of ONFH. THA was performed in 18 hips. Thus, the overall femoral head survival rate was 87.05% (121/139). The success rate was adversely affected by JIC type, but not by aetiology, age, or ARCO stage. The only complication was a subtrochanteric fracture in one patient. CONCLUSION: The SDBS may be an effective method to delay or even terminate the natural progression of ONFH, especially for patients with JIC types B and C1. The SDBS represents a new option for treating early-stage ONFH.

[Reduning Injection protects flu-infected mice by inhibiting infiltration of inflammatory cells in lung and down-regulating cytokine storm].

This study aimed to explore the protective effect of Reduning Injection(RDN) on mice infected by influenza virus A/PR/8(PR8) and its immune regulatory roles during viral infection. In in vivo experiments, female C57 BL/6 mice were randomly divided into phosphate buffered saline(PBS) group, PR8-infected group, oseltamivir treatment group(OSV) and RDN treatment group. After 2 h of PR8 infection, mice in the oseltamivir group were gavaged with oseltamivir 30 mg·kg~(-1), and those in the RDN treatment group were injected intraperitoneally with RDN 1.5 mL·kg~(-1)once per day for seven consecutive days. The body weight of mice in each group was recorded at the same time every morning for 16 consecutive days. The line chart of body weight change was created to analyze the protective effect of RDN on flu-infected mice. The relative mRNA expression of different cytokines(IL-6, TNF-α, MCP-1, IL-1ß, MIP-2, IP-10 and IL-10) in lung samples of flu-infected mice was detected by PCR. Flow cytometry was utilized to analyze the composition of immune cells of mouse BALF samples on day 5 after infection. Mouse macrophage cell line RAW264.7 was planted and treated by different concentrations of RDN(150, 300, 600 µg·mL~(-1)) for 24 h or 48 h, and cell proliferation was detected by CCK-8 assay. RAW264.7 cells and mouse primary peritoneal macrophages were stimulated with synthetic single stranded RNA(R837), which elicited the inflammatory response by mimicking the infection of single-stranded RNA viruses. The expression of cytokines and chemokines in the supernatants of above culture system was detected by ELISA and qPCR. On days 4, 5, 6, 7 and 15 after infection, the body weight loss of mice in the RDN treatment group was alleviated compared with that of PR8-infected mice(P<0.05). RDN treatment obviously reduced lung index and the production of IL-6, TNF-α, MCP-1 and MIP-2 in lung tissues of flu-infected mice(P<0.05). The proportions of macrophages, neutrophils and T cells in mouse BALF samples were analyzed by flow cytometry, and compared with PR8-infected mice, RDN decreased the proportion of macrophages in BALF of flu-infected mice(P<0.05), and the proportion of T cells was recovered dramatically(P<0.001). In CCK-8 assay, the concentrations of RDN(150, 300, 600 µg·mL~(-1)) failed to cause cytotoxicity to RAW264.7 cells. In addition, RDN lowered the expression of inflammatory cytokines such as IL-6, TNF-α,MCP-1, IL-1ß, RANTES, and IP-10 and even anti-inflammatory cytokine IL-10 in R837-induced macrophages. RDN reduced the infiltration of inflammatory macrophages and the production of excessive inflammatory cytokines, alleviated the body weight loss of flu-infected mice. What's more, RDN restored the depletion of T cells, which might prevent secondary infection and deteriorative progression of the disease. Taken together, RDN may inhibit cytokine production and therefore down-regulate cytokine storm during the infection of influenza virus.

Yttrium-mediated red fluorescent carbon dots for sensitive and selective detection of calcium ions.

As the second messenger in cells, calcium ions are indispensable in various physiological activities of the body. In this work, a special red fluorescent carbon dot was designed and synthesized using the secondary hydrothermal method with yttrium, p-phenylenediamine, and ethylene glycol tetraacetic acid as precursors for the detection of calcium ions. The designed carbon dot exhibited bright red fluorescence, and the fluorescence emission wavelength showed good photostability. When the calcium ion concentration was controlled from 0 to 400 µM, the carbon dot tended to respond to fluorescence quenching. At the same time, a test paper experiment was carried out, which proved the potential application of the nano-sensor in detecting calcium ions.

[Exploration and Practice of the Whole-course Care Mode from Hospital to Home for an Advanced Malignant Tumor Patient].

This paper depicted the whole-course care for an advanced cancer patient from hospital to home.In this case,telemedicine was employed to provide guidance on the symptom control,comfort care,psychotherapy,and bereavement counseling.The patient got the holistic care from the whole family and team.The holistic care finally gave a good death of the patient and aided in the recovery of the family members from grief.

[Cryptotanshinone May Induce Ferroptosis of Human Liver Cancer HepG2 Cells].

Objective To observe the effect of cryptotanshinone on the ferroptosis of human liver cancer HepG2 cells. Methods The viability of the HepG2 cells cultured in vitro was determined using the Cell Counting Kit-8(CCK-8),and the half maximal inhibitory concentration(IC50)was calculated.The cell morphology was observed using an inverted microscope.The reactive oxygen species(ROS)level was detected with the 2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)probe.The glutathione(GSH)assay kit was used to determine the GSH level.Western blot analysis was employed to detect the expression of cystine/glutamate antiporter system light chain(xCT)and glutathione peroxidase 4(GPX4),two marker proteins in ferroptosis.Additionally,the cell viability,ROS level,GSH level,and the expression levels of xCT and GPX4 were detected for the cells treated with the ferroptosis inhibitor ferrostain-1(Fer-1),the iron chelator deferoxamine(DFO),and the ROS scavenger N-acetylcysteine(NAC).Results Cryptotanshinone significantly inhibited the cell viability of HepG2 cells with an IC50 of 93.73 µmol/L,and caused the morphological changes and death of the cells.It could significantly induce ROS accumulation,reduce GSH level,and down-regulate the expression of xCT and GPX4 in HepG2 cells.Fer-1,DFO,and NAC can remedy the cryptotanshinone-caused decrease in the cell viability of HepG2 cells.Fer-1 could inhibit cryptotanshinone-induced ROS accumulation,restore GSH level,and recover the expression of xCT and GPX4. Conclusion Cryptotanshinone may increase the accumulation of ROS by inhibiting the expression of xCT and GPX4 to induce the ferroptosis of HepG2 cells.

Transcriptome analysis of mild hypothermia protection against radiation-induced rat lung injury based on RNA-seq. / 基于RNA-SeqæŠ€æœ¯çš„äºšä½Žæ¸©é˜²æŠ¤å¤§é¼ æ”¾å°„æ€§è‚ºæŸä¼¤çš„è½¬å½•ç»„å­¦åˆ†æž.

OBJECTIVES: To analyze the differentially expressed genes (DEGs) with radiation-induced rat lung injury, and to reveal the protective mechanism for mild hypothermia in the radiation-induced lung injury in rats at the transcriptome level. METHODS: A total of 10 male SD rats aged 6-8 weeks were randomly divided into 2 groups to establish a rat model of radiation-induced lung injury, and one group was treated with mild hypothermia. RNA was extracted from left lung tissue of each group, and sequenced by BGISEQ-500 platform. Significance analysis of DEGs was carried out by edgeR software. Gene ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to analyze the gene function. Then 5 key DEGs were verified by real-time reverse transcription PCR (real-time RT-PCR). RESULTS: There were 2 790 DEGs (false discovery rate<0.001, |log2(fold change)|>1) in the mild hypothermia group compared with the model group, in which 2 257 genes were up-regulated and 533 genes were down-regulated. When real-time RT-PCR was used to validate the 5 key genes, the result was consistent with the RNA-seq. GO functional enrichment analysis showed that these DEGs were related to cell binding, metabolic process and cell membrane structure, etc. KEGG pathway enrichment analysis showed that these genes were involved in important biological pathways such as cell adhesion molecules, mammalian target of rapamycin, tight junction, and NF-κB. CONCLUSIONS: The DEGs and pathways related to mild hypothermia protection against radiation-induced lung injury in rats are obtained, which provides an experimental basis for the protection of mild hypothermia against radiation-induced lung injury.

An improved quantitative real-time polymerase chain reaction technology for Helicobacter pylori detection in stomach tissue and its application value in clinical precision testing.

BACKGROUND: Helicobacter pylori (H. pylori) infection is a serious human health threat. The empiric H. pylori treatment paradigm guided by traditional testing technologies has led to antibiotic resistance. Here, we improved the qPCR method to provide technical support for precision H. pylori diagnosis and treatment. METHODS: Two pairs of primers and probes targeting the glmM gene were designed to detect H. pylori, and a multiplex qPCR method was established for virulence factor detection. Then, a rapid urease test (RUT), culturing and qPCR were performed on 141 specimens collected from Xinqiao Hospital of China in 2017 to evaluate the qPCR detection capability. Finally, the H. pylori infectious amount and virulence genes were detected by qPCR. RESULTS: 1. The improved qPCR method which used two pairs of primers had a higher detection rate (100%) and better accuracy (p = 0.000), compared with the qPCR using a pair of primers. It also had better consistency with the bacterial culture than with RUT (Kappa =0.440, p < 0.001). 2. The H. pylori infectious amount was significantly positively associated with gastritis in corpus (p = 0.003) and gastric erosion (p = 0.043). The H. pylori infectious amount in gastric precancerous patients was significantly lower than that in H. pylori-positive patients (p < 0.05), and the infectious H. pylori-vacA s1+ amount was significantly greater than that of H. pylori-vacA s1- (p < 0.05). 3. The vacA s1 frequency was significantly higher than that of vacA m1/cagA+/babA2+ in chronic superficial gastritis (p = 0.000), peptic ulcer (p = 0.037) and gastric erosion (p = 0.009). The H. pylori-vacA+/cagA+/babA2+ frequency showed a significant positive correlation (p < 0.05). CONCLUSIONS: The H. pylori infectious amount and presence of H. pylori virulence factors showed complex correlations with gastric disease occurrence and development. The improved qPCR with good detection performance can be used for quantitative H. pylori detection and testing for the virulence genes vacA s1, vacA m1, cagA and babA2 simultaneously. These findings will provide valuable information for disease diagnosis and treatment.

The effect of the necrotic area on the biomechanics of the femoral head - a finite element study.

BACKGROUND: Femoral head collapse is the key to the progress of osteonecrosis of the femoral head (ONFH), but the causes of collapse are not completely clear. The better understanding of the progress of femoral head collapse will guide the treatment strategy for ONFH patients. The purpose of this study was to evaluate the biomechanical influence of necrosis area on the collapse of the femoral head by finite element analysis. METHODS: CT and MRI data from the hip joint of a healthy volunteer were collected to establish a finite element (FE) model of a normal hip. Subsequently, five categories of osteonecrosis FE models were established by using the normal model and computer software according to China-Japan Friendship Hospital (CJFH) classification for ONFH. The CJFH system includes five types based on the size and location of necrosis lesions in the femoral head (type M, C, L1, L2, and L3) and the stage of ONFH. The collapse indices of each model were analyzed by FE method, including the displacement, peak von Mises stress and stress index of the simulated necrotic area as well as the lateral pillar contact area of the femoral head to acetabular. RESULTS: (1) The displacement increments in the simulated necrotic areas of type M, C, L1, L2, and L3 models were 3.75 µm, 8.24 µm, 8.47 µm, 18.42 µm, and 20.44 µm respectively; the peak von Mises stress decrements were 1.50 MPa, 3.74 MPa, 3.73 MPa, 4.91 MPa, and 4.92 MPa respectively; and the stress indices were 0.04, 0.08, 0.08, 0.27, and 0.27 respectively. (2) The displacement increments in the lateral pillar contact areas of five type models were significantly different (P < 0.001) and increased in sequence as follows: 1.93 ± 0.15 µm, 5.74 ± 0.92 µm, 5.84 ± 1.42 µm, 14.50 ± 3.00 µm, and 16.43 ± 3.05 µm. The peak von Mises stress decrements were also significantly different (P < 0.001) and increased in sequence as follows: 0.52 ± 0.30 MPa, 0.55 ± 0.12 MPa, 0.67 ± 0.33 MPa, 4.17 ± 0.59 MPa, and 4.19 ± 0.60 MPa. (3) The collapse indices including the displacement increments and peak von Mises stress decrements of type L2 and L3 models were markedly higher than those of type M, C, and L1 models (P < 0.001). CONCLUSIONS: The collapse indices of the femoral heads of type L2 and L3 FE models were significantly higher than those of type M, C, and L1. Different areas of necrosis result in varied impact on the femoral head collapse.

Searching for valuable differentially expressed miRNAs in postmenopausal osteoporosis by RNA sequencing.

AIM: Postmenopausal osteoporosis is a systemic and chronic bone disease in women. In order to understand the pathological mechanism of postmenopausal osteoporosis, we aimed to find the potential differentially expressed miRNAs in the disease. METHODS: Firstly, RNA sequencing was used to identify differentially expressed miRNAs, followed by the construction of the miRNA-target mRNA regulatory network. Then, Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes were used to analyze the biological function of target mRNAs. Finally, electronic validation of identified differentially expressed miRNAs and target mRNAs was performed. RESULTS: A total of 33 differentially expressed miRNAs (18 upregulated and 15 downregulated miRNAs) and 6820 miRNA-mRNA pairs were identified. Among which, seven miRNAs with high degree including hsa-miR-17-5p, hsa-miR-1-3p, hsa-miR-193b-3p, hsa-miR-125b-5p, hsa-miR-10b-5p, hsa-miR-100-5p and hsa-miR-30a-3p were obtained in the miRNA-mRNA regulatory network. TGF-beta was the most significantly enriched signaling pathway of target mRNAs. The electronic validation result of hsa-miR-1-3p, hsa-miR-193b-3p, hsa-miR-10b-5p, hsa-miR-100-5p, hsa-miR-133b, hsa-miR-708-5p, CRK, RAB5C, CCND1 and PCYOX1 was consisted with the RNA sequencing analysis. CONCLUSION: Dysfunctional miRNAs may play significant roles in postmenopausal osteoporosis.

Competence of pharmacy mentors: a survey of the perceptions of pharmacy postgraduates and their mentors.

BACKGROUND: Although mentorship can bring many benefits to medical education, mentors' need for professional development is typically ignored. This study aims to acquire insight into the development of pharmacy mentors' competence by comparing differences between mentors' and postgraduates' perspectives. METHODS: We used ANOVAs, independent-sample T-tests and paired-sample T-tests to analyze data collected via an anonymous survey, which included a prepared questionnaire completed by 118 pharmacy mentors and 118 pharmacy postgraduates from 8 Chinese universities and colleges. RESULTS: 1. Research competence, professional knowledge, and communication competence exhibited the highest means. 2. Research competence was highly correlated with communication competence and moderately correlated with professional knowledge, educational competence, academic achievement and supportive competence. 3. Mentors' educational competence was significantly more important to mentors than to postgraduates, and mentors' supportive competence was significantly more important to postgraduates than to mentors. 4. Educational competence, supportive competence and academic achievement were significantly more important to mentors with a bachelor's degree than to mentors with a master's or doctoral degree. 5. Research competence, educational competence and communication competence were significantly more important to female students than male students. CONCLUSIONS: Good mentors should possess three core competencies: research competence, professional knowledge and communication competence. They are related rather than independent. The construction of a harmonious mentoring relationship should take full account of a student's characteristics and expectations because graduate students care more about supportive competence and female students assign greater importance to mentors' competence than male students. There should be more development opportunities for less educated mentors, as they have a greater need to increase their competence than more qualified mentors.