Injectable Phage-Loaded Microparticles Effectively Release Phages to Kill Methicillin-Resistant Staphylococcus aureus.

The increasing prevalence of bacterial multidrug antibiotic resistance has led to a serious threat to public health, emphasizing the urgent need for alternative antibacterial therapeutics. Lytic phages, a class of viruses that selectively infect and kill bacteria, offer promising potential as alternatives to antibiotics. However, injectable carriers with a desired release profile remain to be developed to deliver them to infection sites. To address this challenge, phage-loaded microparticles (Phage-MPs) have been developed to deliver phages to the infection site and release phages for an optimal therapeutic effect. The Phage-MPs are synthesized by allowing phages to be electrostatically attached onto the porous polyethylenimine-modified silk fibroin microparticles (SF-MPs). The high specific surface area of SF-MPs allows them to efficiently load phages, reaching about 1.25 × 1010 pfu per mg of microparticles. The Phage-MPs could release phages in a controlled manner to achieve potent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). Unlike the diffuse biodistribution of free phages post-intraperitoneal injection, Phage-MPs could continuously release phages to effectively boost the local phage concentration at the bacterial infection site after they are intraperitoneally injected into an abdominal MRSA-infected mouse model. In a mouse abdominal MRSA infection model, Phage-MPs significantly reduce the bacterial load in major organs, achieving an efficient therapeutic effect. Furthermore, Phage-MPs demonstrate outstanding biocompatibility both in vitro and in vivo. Overall, our research lays the foundation for a new generation of phage-based therapies to combat antibiotic-resistant bacterial infections.

Causal Connectivity Network Analysis of Ictal Electrocorticogram With Temporal Lobe Epilepsy Based on Dynamic Phase Transfer Entropy.

Temporallobe epilepsy (TLE) has been conceptualized as a brain network disease, which generates brain connectivity dynamics within and beyond the temporal lobe structures in seizures. The hippocampus is a representative epileptogenic focus in TLE. Understanding the causal connectivity in terms of brain network during seizures is crucial in revealing the triggering mechanism of epileptic seizures originating from the hippocampus (HPC) spread to the lateral temporal cortex (LTC) by ictal electrocorticogram (ECoG), particularly in high-frequency oscillations (HFOs) bands. In this study, we proposed the unified-epoch dynamic causality analysis method to investigate the causal influence dynamics between two brain regions (HPC and LTC) at interictal and ictal phases in the frequency range of 1-500 Hz by introducing the phase transfer entropy (PTE) out/in-ratio and sliding window. We also proposed PTE-based machine learning algorithms to identify epileptogenic zone (EZ). Nine patients with a total of 26 seizures were included in this study. We hypothesized that: 1) HPC is the focus with the stronger causal connectivity than that in LTC in the ictal state at gamma and HFOs bands. 2) Causal connectivity in the ictal phase shows significant changes compared to that in the interictal phase. 3) The PTE out/in-ratio in the HFOs band can identify the EZ with the best prediction performance.

Seizure onset zone identification using phase-amplitude coupling and multiple machine learning approaches for interictal electrocorticogram.

Automatic seizure onset zone (SOZ) localization using interictal electrocorticogram (ECoG) improves the diagnosis and treatment of patients with medically refractory epilepsy. This study aimed to investigate the characteristics of phase-amplitude coupling (PAC) extracted from interictal ECoG and the feasibility of PAC serving as a promising biomarker for SOZ identification. We employed the mean vector length modulation index approach on the 20-s ECoG window to calculate PAC features between low-frequency rhythms (0.5-24 Hz) and high frequency oscillations (HFOs) (80-560 Hz). We used statistical measures to test the significant difference in PAC between the SOZ and non-seizure onset zone (NSOZ). To overcome the drawback of handcraft feature engineering, we established novel machine learning models to learn automatically the characteristics of the obtained PAC features and classify them to identify the SOZ. Besides, to handle imbalanced dataset classification, we introduced novel feature-wise/class-wise re-weighting strategies in conjunction with classifiers. In addition, we proposed a time-series nest cross-validation to provide more accurate and unbiased evaluations for this model. Seven patients with focal cortical dysplasia were included in this study. The experiment results not only showed that a significant coupling at band pairs of slow waves and HFOs exists in the SOZ when compared with the NSOZ, but also indicated the effectiveness of the PAC features and the proposed models in achieving better classification performance .

Diagnostic value of high-frequency ultrasound (HFUS) in evaluation of subcutaneous lesions.

BACKGROUND: It is unknown whether high-frequency ultrasound (HFUS) can evaluate invisible subcutaneous lesions. We aimed to investigate the diagnostic value of HFUS in invisible subcutaneous lesions. METHOD: Patients with invisible subcutaneous lesions were prospectively recruited from two centres. Before undergoing biopsy or surgery, each lesion was independently evaluated by two clinicians. One provides a clinical diagnosis by only clinical examination and the other provides an integrated diagnosis by combining clinical examination and HFUS information. Diagnoses were classified as correct, wrong, and indeterminate. A total of 391 lesions from 355 patients were enrolled, including 225 epidermoid cysts, 77 lipomas, 25 pilomatrixomas, 21 haemangiomas, 19 dermatofibromas, 11 dermatofibrosarcoma protuberans (DFSP), 7 neurofibromas, and 6 leiomyomas. Using pathological results as the gold standard, diagnostic performance was compared. RESULTS: The number of correct diagnoses increased from 185 (47.3%) by clinical examination alone to 316 (80.8%) after the addition of HFUS (P < 0.05). Meanwhile, the indeterminate diagnosis rate decreased from 143 (36.6%) to 10 (2.6%). Using HFUS, the accuracy improved significantly for epidermoid cysts (59.6% vs. 86.7%), lipomas (50.6% vs. 94.8%), pilomatrixomas (0% vs. 48.0%), haemangiomas (23.8% vs. 57.1%), and DFSPs (0% vs. 81.8%) (all p < 0.05). However, HFUS did not significantly improve the diagnostic accuracy of dermatofibromas (15.8% vs. 21.1%, p > 0.999), neurofibromas (42.9% vs. 71.4%, p = 0.625), or leiomyomas (16.7% vs. 100%, p = 0.063). CONCLUSION: Combining HFUS and clinical examination can generally improve the diagnostic accuracy and decrease the indeterminacy of invisible subcutaneous lesions, especially epidermoid cysts, lipomas, pilomatrixomas, haemangiomas, and DFSPs. However, for some rare lesions, HFUS cannot provide useful information.

Three-dimensional convolutional neural network model to identify clinically significant prostate cancer in transrectal ultrasound videos: a prospective, multi-institutional, diagnostic study.

Background: Identifying patients with clinically significant prostate cancer (csPCa) before biopsy helps reduce unnecessary biopsies and improve patient prognosis. The diagnostic performance of traditional transrectal ultrasound (TRUS) for csPCa is relatively limited. This study was aimed to develop a high-performance convolutional neural network (CNN) model (P-Net) based on a TRUS video of the entire prostate and investigate its efficacy in identifying csPCa. Methods: Between January 2021 and December 2022, this study prospectively evaluated 832 patients from four centres who underwent prostate biopsy and/or radical prostatectomy. All patients had a standardised TRUS video of the whole prostate. A two-dimensional CNN (2D P-Net) and three-dimensional CNN (3D P-Net) were constructed using the training cohort (559 patients) and tested on the internal validation cohort (140 patients) as well as on the external validation cohort (133 patients). The performance of 2D P-Net and 3D P-Net in predicting csPCa was assessed in terms of the area under the receiver operating characteristic curve (AUC), biopsy rate, and unnecessary biopsy rate, and compared with the TRUS 5-point Likert score system as well as multiparametric magnetic resonance imaging (mp-MRI) prostate imaging reporting and data system (PI-RADS) v2.1. Decision curve analyses (DCAs) were used to determine the net benefits associated with their use. The study is registered at https://www.chictr.org.cn with the unique identifier ChiCTR2200064545. Findings: The diagnostic performance of 3D P-Net (AUC: 0.85-0.89) was superior to TRUS 5-point Likert score system (AUC: 0.71-0.78, P = 0.003-0.040), and similar to mp-MRI PI-RADS v2.1 score system interpreted by experienced radiologists (AUC: 0.83-0.86, P = 0.460-0.732) and 2D P-Net (AUC: 0.79-0.86, P = 0.066-0.678) in the internal and external validation cohorts. The biopsy rate decreased from 40.3% (TRUS 5-point Likert score system) and 47.6% (mp-MRI PI-RADS v2.1 score system) to 35.5% (2D P-Net) and 34.0% (3D P-Net). The unnecessary biopsy rate decreased from 38.1% (TRUS 5-point Likert score system) and 35.2% (mp-MRI PI-RADS v2.1 score system) to 32.0% (2D P-Net) and 25.8% (3D P-Net). 3D P-Net yielded the highest net benefit according to the DCAs. Interpretation: 3D P-Net based on a prostate grayscale TRUS video achieved satisfactory performance in identifying csPCa and potentially reducing unnecessary biopsies. More studies to determine how AI models better integrate into routine practice and randomized controlled trials to show the values of these models in real clinical applications are warranted. Funding: The National Natural Science Foundation of China (Grants 82202174 and 82202153), the Science and Technology Commission of Shanghai Municipality (Grants 18441905500 and 19DZ2251100), Shanghai Municipal Health Commission (Grants 2019LJ21 and SHSLCZDZK03502), Shanghai Science and Technology Innovation Action Plan (21Y11911200), and Fundamental Research Funds for the Central Universities (ZD-11-202151), Scientific Research and Development Fund of Zhongshan Hospital of Fudan University (Grant 2022ZSQD07).

Knowledge, attitude, behaviour, and influencing factors of home-based medication safety among community-dwelling older adults with chronic diseases: a cross-sectional study.

BACKGROUND: Older adults with chronic diseases require long-term medication. However, due to lack of drug knowledge and hypomnesia, older adults with chronic diseases are prone to adverse drug events and increased medical costs. This study aimed to explore the status and influencing factors of home-based medication safety among community-dwelling older adults with chronic diseases in China to provide a basis for follow-up to conduct targeted health education. METHODS: Overall, 427 community-dwelling older adults with chronic diseases participated in this study. The Knowledge, Attitude, and Behaviour of Medication Safety among Older Adults with Chronic Diseases Questionnaire was used to assess their home-based medication safety. Multivariate linear regression was used to identify the factors influencing knowledge, attitude, and behaviour regarding medication safety. RESULTS: The average score of home-based medication safety among older adults with chronic diseases was 68.26 ± 8.96, indicating that they had a moderate grasp of medication safety. The scoring rate of each subscale was ranked from high to low as follows: behaviour (84.51%), knowledge (63.33%), and attitude (47.39%). Stepwise linear regression analysis showed that medication safety knowledge, attitudes, and behaviours were significantly associated with higher monthly income, adverse drug events, and taking medicine several times a day (p < 0.05). Additional influencing factors included having fewer chronic diseases, being female, higher educational attainment, taking medicines multiple kinds a day, better self-care ability, and non-hospitalisation for chronic illnesses (p < 0.05). CONCLUSION: Medical staff and community workers should pay attention to the drug safety of older adults with different characteristics and mobilise their enthusiasm for participation to improve their medication self-management ability. TRIAL REGISTRATION: Chinese Clinical Trial Register: ChiCTR2200060987 ; reg. date: 15/06/2022.

Chronological changes in phase-amplitude coupling during epileptic seizures in temporal lobe epilepsy.

OBJECTIVE: To analyze chronological changes in phase-amplitude coupling (PAC) and verify whether PAC analysis can diagnose epileptogenic zones during seizures. METHODS: We analyzed 30 seizures in 10 patients with mesial temporal lobe epilepsy who had ictal discharges with preictal spiking followed by low-voltage fast activity patterns on intracranial electroencephalography. We used the amplitude of two high-frequency bands (ripples: 80-200 Hz, fast ripples: 200-300 Hz) and the phase of three slow wave bands (0.5-1 Hz, 3-4 Hz, and 4-8 Hz) for modulation index (MI) calculation from 2 minutes before seizure onset to seizure termination. We evaluated the accuracy of epileptogenic zone detection by MI, in which a combination of MI was better for diagnosis and analyzed patterns of chronological changes in MI during seizures. RESULTS: MIRipples/3-4 Hz and MIRipples/4-8 Hz in the hippocampus were significantly higher than those in the peripheral regions from seizure onset. Corresponding to the phase on intracranial electroencephalography, MIRipples/3-4 Hz decreased once and subsequently increased again. MIRipples/4-8 Hz showed continuously high values. CONCLUSIONS: Continuous measurement of MIRipples/3-4 Hz and MIRipples/4-8 Hz could help identify epileptogenic zones. SIGNIFICANCE: PAC analysis of ictal epileptic discharges can help epileptogenic zone identification.

Epileptic seizure focus detection from interictal electroencephalogram: a survey.

Electroencephalogram (EEG) is one of most effective clinical diagnosis modalities for the localization of epileptic focus. Most current AI solutions use this modality to analyze the EEG signals in an automated manner to identify the epileptic seizure focus. To develop AI system for identifying the epileptic focus, there are many recently-published AI solutions based on biomarkers or statistic features that utilize interictal EEGs. In this review, we survey these solutions and find that they can be divided into three main categories: (i) those that use of biomarkers in EEG signals, including high-frequency oscillation, phase-amplitude coupling, and interictal epileptiform discharges, (ii) others that utilize feature-extraction methods, and (iii) solutions based upon neural networks (an end-to-end approach). We provide a detailed description of seizure focus with clinical diagnosis methods, a summary of the public datasets that seek to reduce the research gap in epilepsy, recent novel performance evaluation criteria used to evaluate the AI systems, and guidelines on when and how to use them. This review also suggests a number of future research challenges that must be overcome in order to design more efficient computer-aided solutions to epilepsy focus detection.

Relationships between children-related factors, basic psychological need satisfaction, and multiple happiness among urban empty-nesters in China: a structural equation modeling.

BACKGROUND: Aging and empty-nesting in China are becoming more and more serious. Empty-nesters refer to older adults who were not living with their children, were living alone, or were living independently with their spouses. The mental health of empty-nesters needs timely attention. Satisfying the needs of older adults is primarily dependent on their children. Therefore, this study aimed to explore relationships between children-related factors, basic psychological need satisfaction, and multiple happiness among urban empty-nesters in China. METHODS: This study employs the Children-related Factors Questionnaire (CFQ), the Chinese Version of the Basic Psychological Need Satisfaction (BPNS) Scale, and the Multiple Happiness Questionnaire (MHQ) to explore children-related factors, basic psychological need satisfaction and multiple happiness of urban empty-nesters in Fuzhou, China. A total of 507 samples were recruited by cluster sampling. RESULTS: Factors that affect BPNS include physical condition, the number of children, satisfaction with children's marriage, employment and income, retirement, gender, monthly personal income, and self-care have statistical differences (P < 0.05). Factors that affect MHQ include physical condition, the number of children, satisfaction with children's marriage, employment and income, gender, monthly personal income, living status, and self-care have statistical significances (P < 0.05). Structural equation model results showed that BPNS directly impacted MHQ, and factors about children indirectly affect MHQ through BPNS. The mediating role of BPNS in the relationship between children-related factors and MHQ. CONCLUSION: We should encourage our children to spend more time with the empty-nesters and communicate with them, which could help them relieve their negative emotions, satisfy their psychological needs, and improve their well-being. TRIAL REGISTRATION: Reg date: 20/08/2021; No. ChiCTR2100050175.

Exploring urban empty-nesters' using WeChat influencing factors and quality of life: A qualitative descriptive study.

OBJECTIVE: To explore urban empty-nesters using WeChat influencing factors and experiences of improving their quality of life. METHODS: 14 registered empty-nesters who had used WeChat in Fuzhou communities were recruited via convenience and purposive sampling methods with a qualitative descriptive design. Data were collected through individual, semi-structured, and face-to-face interviews and analyzed according to content analysis. RESULTS: The research revealed two primary themes with associated sub-themes: 1) influencing factors of using WeChat, and 2) quality of life experiences. DISCUSSIONS: Physiological factors, education level, and social support were using WeChat influencing factors by urban empty-nesters. WeChat is a convenient channel to improve empty-nesters' daily lives and a practical platform to meet empty-nesters' needs. Identifying these experiences could help older adults, especially empty-nesters' accept the era of intelligence and provide inspiration and reference for the increasingly normalized empty nest life.

Higher phase-amplitude coupling between ripple and slow oscillations indicates the distribution of epileptogenicity in temporal lobe epilepsy with hippocampal sclerosis.

OBJECTIVE: We assessed the diagnostic utility of the occurrence rate of high-frequency oscillations and modulation index (MI) from intraoperative electrocorticography (ioECoG) in determining the extent of epileptogenicity in mesial temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS). METHODS: We enrolled 17 patients who underwent selective amygdalohippocampectomy (SelAH) for TLE due to HS. We analyzed the occurrence rate of ripples (80-200 Hz) and fast ripples (200-300 Hz); and MI between ripples and 3-4 Hz (MIRipples/3-4 Hz) and fast ripples and 3-4 Hz (MIFRs/3-4 Hz) from the amygdala, hippocampus, and lateral temporal lobe (LTL) pre-SelAH and the LTL post-SelAH, and subsequently categorized the patients into good and poor seizure outcome groups. We compared the occurrence rates and MIs over each region of interest between both groups. Receiver operating characteristic analysis was used to identify the most optimal indicator to predict poor surgical outcomes. RESULTS: In the poor seizure outcome group, an increase in the occurrence rate of ripples was seen in the hippocampus and LTL pre-SelAH and the LTL post-SelAH. The MIRipples/3-4 Hz from the LTL pre-SelAH was the most indicative factor of poor outcome. CONCLUSIONS: High occurrence rate of ripples and MIRipples/3-4 Hz from the LTL showed wide epileptogenicity in TLE patients with poor seizure outcomes after SelAH. Our data suggest that the analysis of the occurrence rate of HFOs and MIHFOs/3-4 Hz from ioECoG, especially from the LTL, can indicate the distribution of epileptogenicity in TLE with HS.

Emulating interactions between microorganisms and tumor microenvironment to develop cancer theranostics.

The occurrence of microorganisms has been confirmed in the tumor microenvironment (TME) of many different organs. Microorganisms (e.g., phage, virus, bacteria, fungi, and protozoa) present in TME modulate TME to inhibit or promote tumor growth in species-dependent manners due to the special physiological and pathological features of each microorganism. Such microorganism-TME interactions have recently been emulated to turn microorganisms into powerful cancer theranostic agents. To facilitate scientists to explore microorganisms-TME interactions further to develop improved cancer theranostics, here we critically review the characteristics of different microorganisms that can be found in TME, their interactions with TME, and their current applications in cancer diagnosis and therapy. Clinical trials of using microorganisms for cancer theranostics are also summarized and discussed. Moreover, the emerging technology of whole-metagenome sequencing that can be employed to precisely determine microbiota spectra is described. Such technology enables scientists to gain an in-depth understanding of the species and distributions of microorganisms in TME. Therefore, scientists now have new tools to identify microorganisms (either naturally present in or introduced into TME) that can be used as effective probes, monitors, vaccines, or drugs for potentially advancing cancer theranostics to clinical applications.

Protein nanoparticles directed cancer imaging and therapy.

Cancer has been a serious threat to human health. Among drug delivery carriers, protein nanoparticles are unique because of their mild and environmentally friendly preparation methods. They also inherit desired characteristics from natural proteins, such as biocompatibility and biodegradability. Therefore, they have solved some problems inherent to inorganic nanocarriers such as poor biocompatibility. Also, the surface groups and cavity of protein nanoparticles allow for easy surface modification and drug loading. Besides, protein nanoparticles can be combined with inorganic nanoparticles or contrast agents to form multifunctional theranostic platforms. This review introduces representative protein nanoparticles applicable in cancer theranostics, including virus-like particles, albumin nanoparticles, silk protein nanoparticles, and ferritin nanoparticles. It also describes the common methods for preparing them. It then critically analyzes the use of a variety of protein nanoparticles in improved cancer imaging and therapy.

Synthesis of selective PAK4 inhibitors for lung metastasis of lung cancer and melanoma cells

The p21 activated kinase 4 (PAK4) is serine/threonine protein kinase that is critical for cancer progression. Guided by X-ray crystallography and structure-based optimization, we report a novel subseries of C-3-substituted 6-ethynyl-1H-indole derivatives that display high potential and specificity towards group II PAKs. Among these inhibitors, compound 55 exhibited excellent inhibitory activity and kinase selectivity, displayed superior anti-migratory and anti-invasive properties against the lung cancer cell line A549 and the melanoma cell line B16. Compound 55 exhibited potent in vivo antitumor metastatic efficacy, with over 80% and 90% inhibition of lung metastasis in A549 or B16-BL6 lung metastasis models, respectively. Further mechanistic studies demonstrated that compound 55 mitigated TGF-β1-induced epithelial-mesenchymal transition (EMT).

Seizure Onset Zone Identification Based on Phase-Amplitude Coupling of Interictal Electrocorticogram.

Presurgical localization from interictal electrocorticogram (ECoG) and resection of seizure onset zone (SOZ) are difficult processes to achieve seizure freedom. Recently, high frequency oscillations (HFOs) have been recognized as reliable biomarkers for epilepsy surgery which has a relation with the phase of low frequency activities in ECoG. Considering the recent valid biomarker for epilepsy surgery, we hypothesize that the approach of coupling between HFOs and low frequency phases differs SOZ from non-seizure onset zone (NSOZ). This study proposes phase-amplitude coupling (PAC) method to identify SOZ by measuring whether the amplitude of HFOs is coupled with a phase at 2-34 Hz in ECoG. Besides, three machine learning models for PAC-based features are designed for SOZ detection. Four patients with focal cortical dysplasia (FCD) are examined to observe efficiency. Experimental results indicate that the mode of coupling is a potential feature to detect SOZ.Clinical relevance- This suggests the PAC feature between low frequency phase and HFO amplitude may be used as a candidate biomarker to detect SOZ.

Dynamic theta/beta ratio of clinical EEG in Alzheimer's disease.

BACKGROUND: EEG of a resting state in Alzheimer disease (AD) patients and healthy controls (HC) are analyzed to identify the characteristics of EEG in AD. NEW METHOD: A dynamic box plot approach to the theta/beta ratio with various window durations is proposed to analyze EEG. RESULTS: Spectral results during a resting state in AD patients demonstrate the effect of relatively greater power in the low-frequency bands (i.e. 'slowing down' of the EEG). A significant difference is observed in the dynamic distribution of the theta/beta ratio in the AD and HC groups, which is related to the effect of 'slowing down'. There is a more obvious visual separation between the theta/beta ratio results for the AD and HC groups with increasing window durations. Variability of the theta/beta ratio can be observed with shorter window durations with a dynamic functional box plot. This provides a better classification accuracy by using the dynamic theta/beta ratio as a sensor to discriminate AD EEG from HC EEG by using the receiver operating characteristics (ROC) curve and the area under curve (AUC) with various window durations. COMPARISON WITH EXISTING METHOD(S): EEG spectral analysis and theta/beta ratio used to evaluate EEG typically rely on long time averaging. CONCLUSIONS: The dynamic box plot approach to the theta/beta ratio with various window durations provides the possibility of observing features of the EEG. The dynamic theta/beta ratio is a better sensor to discriminate AD EEG from HC EEG. Moreover, the reliability and accuracy of results can be increased by combining spectral analysis and the dynamic box plot approach to theta/beta ratio with various window durations.

Efficacy and safety of weekly rifapentine and isoniazid for tuberculosis prevention in Chinese silicosis patients: a randomized controlled trial.

OBJECTIVE: The aim was to evaluate the efficacy, safety and completion rate of 3-month, once-weekly rifapentine and isoniazid for tuberculosis (TB) prevention among Chinese silicosis patients. METHODS: Male silicosis patients without human immunodeficiency virus infection, aged 18 years to 65 years, with or without latent TB infection, were randomized 1:1 to receive rifapentine/isoniazid under direct observation (3RPT/INH group) or were untreated (observation group). Active TB incidence was compared between the two groups with 37 months of follow-up. Safety profile and complete rates were evaluated. RESULTS: A total of 1227 adults with silicosis were screened; 513 eligible participants were enrolled and assigned to 3RPT/INH (n = 254) vs. observation (n = 259). Twenty-eight participants were diagnosed with active TB, and 9 and 19 in the 3RPT/INH group and observation groups, respectively. In the intention-to-treat analysis, the cumulative active TB rate was 3.5% (9/254) in the 3RPT/INH group and 7.3% (19/259) in the observation group (log rank p 0.055). On per protocol analysis, the cumulative active TB rates were 0.7% (1/139) and 7.3% (19/259), respectively (log rank p 0.01). Owing to an unexpected high frequency of adverse events (70.4%) and Grade 3 or 4 AEs (7.9%), the completion rate of the 3RPT/INH regimen was 54.7% (139/254). Twenty-six (10.8%) participants had flu-like systemic drug reactions; five (2.1%) experienced hepatotoxicity. DISCUSSION: Weekly rifapentine/isoniazid prophylaxis prevented active TB among Chinese people with silicosis when taken, irrespective of LTBI screening; efficacy was reduced by lack of compliance. The regimen must be used with caution because of the high rates of adverse effects. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number: NCT02430259.

Effectiveness comparisons of acupuncture for diabetic nephropathy proteinuria: A systematic review and meta-analysis: study protocol.

INTRODUCTION: Diabetic nephropathy (DN) is one of the microvascular complications of diabetes (DM). Proteinuria is the most important clinical feature of DN and an independent risk factor for the progression of DN. Therefore, reducing urinary protein is the primary goal of DN treatment. Acupuncture has long been widely used in the treatment of DN. Therefore, this paper conducted a meta-analysis of the clinical efficacy of acupuncture in the treatment of DN proteinuria, in order to comprehensively analyze the role of acupuncture in the treatment of DN. METHODS AND ANALYSIS: We will search for PubMed, Cochrane Library, AMED, EMbase, WorldSciNet; Nature, Science online and China Journal Full-text Database (CNKI), China Biomedical Literature CD-ROM Database (CBM), and related randomized controlled trials included in the China Resources Database. The time is limited from the construction of the library to September 2019.We will use the criteria provided by Cochrane 5.1.0 for quality assessment and risk assessment of the included studies, and use the Revman 5.3 and Stata13.0 software for meta-analysis of the effectiveness, recurrence rate, and symptom scores of DN proteinuria. ETHICS AND DISSEMINATION: This systematic review will evaluate the efficacy and safety of acupuncture for DN proteinuria. Because all of the data used in this systematic review and meta-analysis has been published, this review does not require ethical approval. Furthermore, all data will be analyzed anonymously during the review process Trial. TRIAL REGISTRATION NUMBER: PROSPERO CRD42019139705.

Effects and mechanism of low-intensity pulsed ultrasound on extracellular matrix in rabbit knee osteoarthritis / 中国骨伤

<p><b>OBJECTIVE</b>To observe the effects of low-intensity pulsed ultrasound (LIPUS) on repairing extracellular matrix in rabbit knee osteoarthritis and analyze its mechanism.</p><p><b>METHODS</b>Sixty adult female rabbits with an average weight of (2.0 ± 0.2) kg, were divided randomly into two groups (experimental group and control group, 30 rabbits in each group). All rabbits were replicated in right knees by Hulth method for knee osteoarthritis model. Two weeks after operation, the rabbits in experimental group were treated with LIPUS, and the ultrasonic frequency was (800 ± 5%)KHz and the maximum intensities of spatially averaged and time averaged (SATA) was (50 ± 10%) mw/cm2, for 1 time a day and every time 20 min, while the rabbits in control group were treated with sham LIPUS,the same operation with experimental group but without energy output. At the 2, 4, 8 weeks after treatment, 10 rabbits in each group were randomly killed for each time. The general changes of cartilage and its histopathological changes by HE staining were observed; the expression of collagen type II, proteoglycan, MMP-3, 7, 13 in cartilage were analyzed by immunohistochemical and RT-PCR technique; and the expression of NO in cartilage was analyzed by nitrate reduction method.</p><p><b>RESULTS</b>On the same observed time point, the damage degree of cartilage in experimental group was slighter than that of control group (P < 0.01), the expression of MMP-3, 7, 13 and NO in cartilage in experimental group was lower than that of control group (P < 0.01) while collagen type II and proteoglycan was higher than that of control group (P < 0.01).</p><p><b>CONCLUSION</b>Low-intensity pulsed ultrasound can repair the damaged cartilage by reducing the expression of MMP-3, 7, 13, inhibiting the secretion of NO and promoting the synthesis of collagen type II and proteoglycan in cartilage.</p>

Small needle-knife for the treatment of tennis elbow according to its classification / 中国骨伤

<p><b>OBJECTIVE</b>To observe clinical effect of different treatments for tennis elbow with small needle-knife according to its classification.</p><p><b>METHODS</b>From March 2011 to December 2012,100 patients with 123 tennis elbows were treated with small needle-knife, including 36 males and 64 females, ranging in age from 29 to 76 years old (averaged, 49 years old). The course of disease ranged from 3 months to 2 years (averaged, 7.2 months). According to the classification, 46 elbows were with extra-articular type, 34 elbows with intra-articular type, 20 elbows with mixed type. All the patients were treated with small needle-knife by using different methods according to its classification.</p><p><b>RESULTS</b>All patients were followed up for 6 to 12 months with an average of 8.2 months. After treatment, the symptoms and signs of the patients improved significantly (P < 0.01). According to the criteria of the Verhaar scoring system, 35 of 46 patients with extra-articular type got an excellent result, 9 good, 2 fair; 24 of 34 patients with intra-articular type got an excellent result, 9 good, 1 fair; 9 of 20 patients with mixed type got an excellent result, 8 good, 3 fair.</p><p><b>CONCLUSION</b>The causes of tennis elbow can not be explained by single pathogenesy, the patients with tennis elbow should be treated with different methods according to its classification, and the therapeutic effects can be improved.</p>