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Natural macromolecules have been used to adsorb pollutants including heavy metal ions and organic dyes due to low-cost, accessible, biodegradable, and eco-friendly advantages. Pectin, an important natural polymer, possesses abundant carboxyl and hydroxyl functional groups that can interact with the metal and organic cations via electrostatic interaction; as well as be modified by other chemicals for preparing hybrid and composite materials. The resultant materials have been employed to remove pollutants from aqueous solution; the importance of chemical composition was unlocked. Here, we reviewed contaminant removal by pectin, and pectin-based hybrid and composite materials, and highlighted the role of functional groups on pollutant removal. The removal of heavy metal ions was mainly due to surface coordination, while that of organic cations to electrostatic interactions of the functional groups. Moreover, the influence of initial contaminant concentration was critically discussed. The comprehensive review can provide valuable information on pectin and its application in contaminant removal., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Congenital cytomegalovirus (cCMV) infection is the leading infectious cause of neurodevelopmental disorders. However, the neuropathogenesis remains largely elusive due to a lack of informative animal models. In this study, we developed a congenital murine CMV (cMCMV) infection mouse model with high survival rate and long survival period that allowed long-term follow-up study of neurodevelopmental disorders. This model involves in utero intracranial injection and mimics many reported clinical manifestations of cCMV infection in infants, including growth restriction, hearing loss, and impaired cognitive and learning-memory abilities. We observed that abnormalities in MRI/CT neuroimaging were consistent with brain hemorrhage and loss of brain parenchyma, which was confirmed by pathological analysis. Neuropathological findings included ventriculomegaly and cortical atrophy associated with impaired proliferation and migration of neural progenitor cells in the developing brain at both embryonic and postnatal stages. Robust inflammatory responses during infection were shown by elevated inflammatory cytokine levels, leukocyte infiltration, and activation of microglia and astrocytes in the brain. Pathological analyses and CT neuroimaging revealed brain calcifications induced by cMCMV infection and cell death via pyroptosis. Furthermore, antiviral treatment with ganciclovir significantly improved neurological functions and mitigated brain damage as shown by CT neuroimaging. These results demonstrate that this model is suitable for investigation of mechanisms of infection-induced brain damage and long-term studies of neurodevelopmental disorders, including the development of interventions to limit CNS damage associated with cCMV infection.

Objective: To investigate the clinical effect of biofeedback and electrical stimulation therapy (BFES) combined with Sabale capsules (SC) on chronic prostatitis / chronic pelvic pain syndrome (CP/CPPS)., Methods: A total of 140 outpatients meeting CP/CPPS diagnostic and research criteria in the Second Affiliated Hospital of Xi'an Jiaotong University were randomly divided into groups A (blank control), B (BFES intervention), C (SC intervention) and D (BFES+SC intervention), 35 cases in each group. The patients in group A were left untreated, while those in groups B, C and D received BFES, SC and BFES+SC, respectively, all for 12 weeks. Then the patients were followed up at 30 days after treatment and the urinary flow rate and NIH-CPSI scores were obtained and compared with the baseline., Results: In comparison with the baseline, the total NIH-CPSI scores after intervention were significantly decreased in groups B, (［27.30 ± 2.44］ vs ［19.43 ± 2.33］), C (［26.77 ± 2.54］ vs ［19.40 ± 2.75］) and D (［27.67 ± 3.69］ vs ［15.57 ± 1.94］) (all P < 0.05), and so were the individual item scores in pain or discomfort (［12.50 ± 1.94］ vs ［9.40 ± 2.01］, ［11.93 ± 1.64］ vs ［9.23 ± 1.96］, and ［12.33 ± 2.20］ vs ［7.50 ± 1.55］), urination symptoms (［6.07 ± 1.57］ vs ［3.83 ± 1.05］, ［5.97 ± 1.33］ vs ［3.77 ± 1.14］, and ［6.20 ± 1.88］ vs ［2.87 ± 0.94］), quality of life (QOL) (［8.73 ± 1.62］ vs ［6.20 ± 1.42］, ［8.87 ± 1.25］ vs ［6.40 ± 1.59］, and ［9.13 ± 1.70］ vs ［5.20 ± 1.40］) (all P < 0.05), while the maximum urinary flow rate (Qmax) was remarkably increased (［15.72 ± 2.38］ vs ［19.73 ± 2.85］, ［16.20 ± 2.44］ vs ［19.46 ± 2.48］, and ［15.83 ± 2.52］ vs ［22.49 ± 2.76］) (all P < 0.05), and so was the average urinary flow rate (Qavg) (［9. 282 ± 1.52］ vs ［11.27 ± 1.95］, ［8.97 ± 1.25］ vs ［11.16 ± 1.74］, and ［9.20 ± 1.36］ vs ［13.50 ± 2.30］) (all P < 0.05). The decrease in NIH-CPSI total and item scores and increase in Qmax and Qavg after treatment were more significant in group D than in B and C (P < 0.05), but showed no statistically significant difference between groups B and C (P > 0.05). Nor was any significant change observed in the above parameters in group A after treatment ( P > 0.05)., Conclusions: Biofeedback and electrical stimulation therapy combined with Sabale capsules can alleviate urination dysfunction, pelvic floor tension myalgia and other symptoms and significantly improve the QOL of CP/CPPS patients.

On the basis of the Conservation of Resource (COR) theory and using the Job Demands-Resources (JD-R) model, this study examines the relationships among job demands and job resources of online teaching (JD-OT and JR-OT), perceived instructional efficacy of OT (PIE-OT), mindfulness in teaching (MiT), and emotional exhaustion (EE) to understand the psychological stress experienced by teachers engaged in OT and how mindfulness has moderating effects on relieving anxiety and preventing burnout. A total of 476 teachers with OT experience completed online a self-report survey with items adapted from related scales. The hypotheses were validated using structural equation modeling. Causal relationships were assessed using path analysis, and multi-group analysis was performed to examine the moderating effect of MiT. JD-OT has significant and negative impact on PIE-OT, JR-OT has significant and positive impact on PIE-OT, and PIE-OT has significant and negative impact on EE. Moreover, PIE-OT mediates the positive relationship of JD-OT with EE and the negative relationship of JR-OT with EE. The moderating role of MiT in the relationship of JD-OT and JR-OT with PIE-OT was also validated. In OT work environments, teachers have great need and desire for JR, which can have a positive impact on PIE. Mindfulness training contributes to improving OT efficacy and reducing EE. Enhancing teachers' MiT enables them to deal with demands from work and their superiors and motivates them to respond with ease to the stressful external environment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hsieh, Ho, Li and Liang.)

Background: Drug-resistant tuberculosis (DR-TB), obesity, and malnutrition are growing public health problems in the world. However, little has discussed the impact of different BMI status on the emergence of TB drug resistance. We aimed to explore the drug-resistant profiles of DR-TB and its clinical predictors among underweight, overweight or obesity population., Methods: 8957 newly diagnosed TB cases with drug susceptibility results and BMI data in Shandong China, from 2004 to 2019 were enrolled. Multivariable and univariable logistic regression models were applied to investigate the impact of BMI on different drug-resistance. Clinical predicators and drug-resistant profiles of DR-TB among obesity, underweight, normal TB group were also described., Results: Among 8957 TB cases, 6417 (71.64%) were normal weight, 2121 (23.68%) were underweight, 373 (4.16%) were overweight, and 46 (0.51%) were obese. The proportion of drug resistance and co-morbidity among normal weight, underweight, overweight, obese TB groups were 18.86%/18.25%/20.38%/23.91% (DR-TB), 11.19%/11.74%/9.65%/17.39% (mono-resistant tuberculosis, MR-TB), 3.41%/3.06%/5.36%/0.00% (multidrug resistant tuberculosis, MDR-TB), 4.21%/3.39%/5.36%/6.52% (polydrug resistant tuberculosis, PDR-TB), 10.57%/8.44%/19.57%/23.91% (co-morbidity), respectively. Compared with normal weight group, underweight were associated with lower risk of streptomycin-related resistance (OR 0.844, 95% CI 0.726-0.982), but contributed to a higher risk of MR-TB (isoniazid) (odds ratio (OR) 1.347, 95% CI 1.049-1.730; adjusted OR (aOR) 1.31, 95% CI 1.017-1.686), P < 0.05. In addition, overweight were positively associated with MDR-TB (OR 1.603, 95% CI 1.002-2.566; aOR 1.639, 95% CI 1.02-2.633), isoniazid + rifampicin + streptomycin resistance (OR 1.948, 95% confidence interval (CI): 1.061-3.577; aOR 2.113, 95% CI 1.141-3.912), Any isoniazid + streptomycin resistance (OR 1.472, 95% CI 1.013-2.14; aOR 1.483, 95% CI 1.017-2.164), P < 0.05., Conclusions: The higher risk of MDR-TB, isoniazid + rifampicin + streptomycin resistance, Any isoniazid + streptomycin resistance, and co-morbidity among overweight population implies that routine screening for drug sensitivity and more attention on co-morbidity among overweight TB cases may be necessary. In addition, underweight TB cases have a higher risk of isoniazid resistance. Our study suggests that an in-depth study of the interaction between host metabolic activity and infection of DR-TB may contribute more to novel treatment options or preventive measures, and accelerate the implementation of the STOP TB strategy., (© 2021. The Author(s).)

Microorganisms play an important role in nutrient cycling and ecosystem stability. This experiment studied the conservation management approaches [control without fertilizer (CK); fertilizer and different mulching based straw mulching (SM), plastic mulching (PM), ridge-furrow with plastic mulching (RFPFM), and green manure (GM)] effects on the soil microbial community structures in spring corn (Zea Mayis) dry land. The results showed that the bacterial phylum mainly included Proteobacteria (28.2%-36.8%), Acidobacteriota (9.1%-17.9%), Bacteroidota (5.6%-8.9%) and Actinobacteria (3.1-6.2%). The most richness fungal components were Ascomycota (35.2%-44.2%), Basidiomycota (3.3%-12%) and Mortierellomycota (3.4%-6.6%). Additionally, the highest Chao1 and abundance-based coverage estimator (ACE) indexes of bacteria (2931.9 and 2953.7) and fungi (1083.316 and 1100.650) were present in RFPFM that indicating the richest microbial abundance, the highest Shannon and Simpson indexes was exist in PM (9.332 and 0.996) for bacteria and RFPFM (6.753 and 0.974) for fungi. Therefore, this study reveals the conservation management of fertilizer addition and mulching management obviously promoted microbial diversity and altered the superior microbial distribution that provides a potential way for agricultural sustainable management approaches in production practice during circular economy., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Severe Coronavirus Disease 2019 (COVID-19) is characterized by numerous complications, complex disease, and high mortality, making its treatment a top priority in the treatment of COVID-19. Integrated traditional Chinese medicine (TCM) and western medicine played an important role in the prevention, treatment, and rehabilitation of COVID-19 during the epidemic. However, currently there are no evidence-based guidelines for the integrated treatment of severe COVID-19 with TCM and western medicine. Therefore, it is important to develop an evidence-based guideline on the treatment of severe COVID-19 with integrated TCM and western medicine, in order to provide clinical guidance and decision basis for healthcare professionals, public health personnel, and scientific researchers involved in the diagnosis, treatment, and care of COVID-19 patients. We developed and completed the guideline by referring to the standardization process of the "WHO handbook for guideline development", the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, and the Reporting Items for Practice Guidelines in Healthcare (RIGHT)., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Recent studies have identified an increased risk of hepatocellular carcinoma (HCC) in autoimmune hepatitis (AIH). Sex and regional disparities in incidence of HCC in AIH continue to be reported worldwide. Nevertheless, the magnitude of this gap remains unknown., Method: We searched several databases including PubMed, Embase, Web of Science, Cochrane Library, Wanfang Data, CNKI and SinoMed. Incidence rates of HCC in AIH were combined and analyzed following the EBayes method. Incidence rate ratios were pooled to assess the sex differences. The impact of population difference, sex, age, cirrhotic condition was further analyzed with subgroup analysis and linear regression analysis., Result: 39 studies meeting our eligibility criteria were chosen for the analysis. The pooled incidence rate of HCC in AIH was 3.54 per 1000 person years (95% CI 2.76-4.55). Pooled IRR for the risk of HCC in male AIH patients compared to female was 2.16 (95% CI 1.25-3.75), with mild heterogeneity among studies. The pooled HCC incidence rate in AIH by continents was as follows: Europe 2.37 per 1000 person-years (95% CI 1.45-3.88), Asia 6.18 per 1000 person-years (95%CI 5.51-6.93), North America 2.97 per 1000 person-years (95%CI 2.40-3.68), Oceania 2.60 (95%CI 0.54-7.58). The pooled HCC incidence rate in AIH-related cirrhosis by continent was as follows: Europe 6.35 per 1000 person-years (95%CI 3.94-10.22), Asia 17.02 per 1000 person-years (95%CI 11.18-25.91), North America 10.89 per 1000 person-years (95%CI 6.69-17.74)., Conclusion: A higher HCC incidence in AIH was observed among male and in Asian populations. Cirrhosis status at AIH diagnosis is significantly associated with an increased incidence rate for HCC, and routine HCC surveillance is recommended for patients with AIH cirrhosis, especially for those in Asia., (© 2021. Asian Pacific Association for the Study of the Liver.)

Direct-to-consumer genetic testing (DTCGT) is gaining popularity in Hong Kong (HK). As DTCGT forgoes specialist medical involvement, healthcare professionals have raised concerns regarding its validity, utility, and the public's ability to interpret DTCGT results. Thus, genetic counseling (GC) is recommended to facilitate understanding of DTCGT. This study aimed to investigate HK public's perception toward DTCGT and the importance of GC in DTCGT. A total of 304 HK adults were invited to complete a 37-item survey online. Participants' genomic literacy, understanding and attitude toward DTCGT and GC, and responses to a mock DTCGT scenario were assessed. 48% of participants were aware of DTCGT while 82% indicated an interest. 30% of participants were aware of GC services in HK; 49% were interested in GC services for understanding DTCGT results. Participants scored on average 7.6/11 in the genomic sequencing knowledge scale and were weak in limitations of genomic testing. In the mock DTCGT scenario, 73% of participants expressed concern with the positive results initially. After being explained limitations of DTCGT, 40% of participants reported decreased concern. Reduced perceived helpfulness in medical management and lifestyle modification were also reported by 35% and 27%, respectively. This HK population demonstrated a high level of awareness and interest in DTCGT. As potential DTCGT users, they might experience excess concern and overestimate the usefulness of positive DTCGT results, particularly in medical management. The importance of GC to educate and guide interpretation of DTCGT results is supported; yet the awareness and access of GC services is inadequate in HK., (© 2021 National Society of Genetic Counselors.)

In this study, the wear behavior of a heat-treatable Al-7Si-0.5Mg-0.5Cu alloy fabricated by selective laser melting was investigated systematically. Compared with the commercial homogenized AA2024 alloy, the fine secondary phase of the SLM Al-Cu-Mg-Si alloy leads to a low specific wear rate (1.8 ± 0.11 × 10 -4 mm 3 (Nm) -1 ) and a low average coefficient of friction (0.40 ± 0.01). After the T6 heat treatment, the SLM Al-Cu-Mg-Si alloy exhibits a lower specific wear rate (1.48 ± 0.02 × 10 -4 mm 3 (Nm) -1 ), but a similar average coefficient of friction (0.34 ± 0.01) as the heat-treated AA2024 alloy. Altogether, the SLM Al-3.5Cu-1.5Mg-1Si alloy is suitable for the achievement of not only superior mechanical performance, but also improved tribological properties.

In the past two decades, testicular tissue grafting and xenografting have been well established, with the production of fertilization-competent sperm in some studies. However, few studies have been carried out to observe the development of grafted prepubertal testicular tissue of rats and compare the biological differences between in situ testis and grafted testis. In this study, we established the prepubertal testicular tissue xenografting model using a 22-day-old rat and evaluated certain parameters, including testicular histology, testosterone production, and ultrastructure of the grafted testes. We also assessed gene expression of cell proliferation markers, testicular cell markers, and antioxidative defense system. Our results showed that 47 days after transplantation, intratesticular testosterone concentration was not significantly altered; however, cell proliferation, spermatogenesis, and Sertoli cell markers in the transplanted testes were significantly disrupted compared with the control group, accompanied by aggravated apoptosis and oxidative damage. Moreover, the transplanted testes showed smaller tubular diameter and disrupted spermatogenic epithelium with apparent vacuoles, distorted and degenerated germ cells with obscure nuclear margin, and no spermatids in the center of the tubules. Although testis xenografting has been extensively tested and attained great achievement in other species, the prepubertal rat testicular tissue xenografting to immunodeficient mice exhibited obvious spermatogenesis arrest and oxidative damage. The protocol still needs further optimization, and there are still some unknown factors in prepubertal rat testes transplantation., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2021 Yu-Bo Ma et al.)

Background: Hypoxemia frequently occurs during bronchoscopy. High-flow nasal cannula (HFNC) oxygen therapy may be a feasible alternative to prevent the deterioration of gas exchange during bronchoscopy. With the convenience of clinical use in mind, we modified an HFNC using a single cannula. This clinical trial was designed to test the hypothesis that a modified HFNC would decrease the proportion of patients with a single moment of peripheral arterial oxygen saturation (SpO 2 ) < 90% during bronchoscopy., Methods: In this single-center, prospective randomized controlled trial, hospitalized patients in the respiratory department in need of diagnostic bronchoscopy were randomly assigned to a modified HFNC oxygen therapy group or a conventional oxygen therapy (COT) group. The primary outcome was the proportion of patients with a single moment of SpO 2  < 90% during bronchoscopy., Results: Eight hundred and twelve patients were randomized to the modified HFNC (n = 406) or COT (n = 406) group. Twenty-four patients were unable to cooperate or comply with bronchoscopy. Thus, 788 patients were included in the analysis. The proportion of patients with a single moment of SpO 2  < 90% during bronchoscopy in the modified HFNC group was significantly lower than that in the COT group (12.5% vs. 28.8%, p < 0.001). There were no significant differences in the fraction of inspired oxygen between the two groups. The lowest SpO 2 during bronchoscopy and 5 min after bronchoscopy in the modified HFNC group was significantly higher than that in the COT group. Multivariate analysis showed that a baseline forced vital capacity (FVC) < 2.7 L (OR, 0.276; 95% CI, 0.083-0.919, p = 0.036) and a volume of fluid instilled > 60 ml (OR, 1.034; 95% CI, 1.002-1.067, p = 0.036) were independent risk factors for hypoxemia during bronchoscopy in the modified HFNC group., Conclusions: A modified HFNC could decrease the proportion of patients with a single moment of SpO 2  < 90% during bronchoscopy. A lower baseline FVC and large-volume bronchoalveolar lavage may predict desaturation during bronchoscopy when using a modified HFNC. Trial registration ClinicalTrials. Gov: NCT02606188. Registered 17 November 2015., (© 2021. The Author(s).)

Chest wall tumors are a relatively uncommon disease in clinical practice. Most of the published studies about chest wall tumors are usually single-center retrospective studies, involving few patients. Therefore, evidences regarding clinical conclusions about chest wall tumors are lacking, and some controversial issues have still to be agreed upon. In January 2019, 73 experts in thoracic surgery, plastic surgery, science, and engineering jointly released the Chinese Expert Consensus on Chest Wall Tumor Resection and Chest Wall Reconstruction (2018 edition). After that, numerous experts put forward new perspectives on some academic issues in this version of the consensus, pointing out the necessity to further discuss the points of contention. Thus, we conducted a survey through the administration of a questionnaire among 85 experts in the world. Consensus has been reached on some major points as follows. (I) Wide excision should be performed for desmoid tumor (DT) of chest wall. After excluding the distant metastasis by multi-disciplinary team, solitary sternal plasmacytoma can be treated with extensive resection and adjuvant radiotherapy. (II) Wide excision with above 2 cm margin distance should be attempted to obtain R0 resection margin for chest wall tumor unless the tumor involves vital organs or structures, including the great vessels, heart, trachea, joints, and spine. (III) For patients with chest wall tumors undergoing unplanned excision (UE) for the first time, it is necessary to carry out wide excision as soon as possible within 1-3 months following the previous surgery. (IV) Current Tumor Node Metastasis staging criteria (American Joint Committee on Cancer) of bone tumor and soft tissue sarcoma are not suitable for chest wall sarcomas. (V) It is necessary to use rigid implants for chest wall reconstruction once the maximum diameter of the chest wall defect exceeds 5 cm in adults and adolescents. (VI) For non-small cell lung cancer (NSCLC) invading the chest wall, wide excision with neoadjuvant and/or adjuvant therapy are recommended for patients with stage T 3-4 N 0-1 M 0 . As clear guidelines are lacking, these consensus statements on controversial issues on chest wall tumors and resection could possibly serve as further guidance in clinical practice during the upcoming years., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/tlcr-21-935). Dr. ISS reports that he had received grants from On Target Laboratories; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events form Intuitive Surgical, Inc., Cambridge Medical Robotics and Auris Medical. Dr. XY serves as an unpaid editorial board member of Translational Lung Cancer Research from July 2021 to June 2023. The other authors have no conflicts of interest to declare., (2021 Translational Lung Cancer Research. All rights reserved.)

The optical design and performance of the recently opened 13A biological small-angle X-ray scattering (SAXS) beamline at the 3.0 GeV Taiwan Photon Source of the National Synchrotron Radiation Research Center are reported. The beamline is designed for studies of biological structures and kinetics in a wide range of length and time scales, from angstrom to micrometre and from microsecond to minutes. A 4 m IU24 undulator of the beamline provides high-flux X-rays in the energy range 4.0-23.0 keV. MoB 4 C double-multilayer and Si(111) double-crystal monochromators (DMM/DCM) are combined on the same rotating platform for a smooth rotation transition from a high-flux beam of ∼4 × 10 14  photons s -1 to a high-energy-resolution beam of ΔE/E ≃ 1.5 × 10 -4 ; both modes share a constant beam exit. With a set of Kirkpatrick-Baez (KB) mirrors, the X-ray beam is focused to the farthest SAXS detector position, 52 m from the source. A downstream four-bounce crystal collimator, comprising two sets of Si(311) double crystals arranged in a dispersive configuration, optionally collimate the DCM (vertically diffracted) beam in the horizontal direction for ultra-SAXS with a minimum scattering vector q down to 0.0004 Å -1 , which allows resolving ordered d-spacing up to 1 µm. A microbeam, of 10-50 µm beam size, is tailored by a combined set of high-heat-load slits followed by micrometre-precision slits situated at the front-end 15.5 m position. The second set of KB mirrors then focus the beam to the 40 m sample position, with a demagnification ratio of ∼1.5. A detecting system comprising two in-vacuum X-ray pixel detectors is installed to perform synchronized small- and wide-angle X-ray scattering data collections. The observed beamline performance proves the feasibility of having compound features of high flux, microbeam and ultra-SAXS in one beamline., (open access.)

Background: Aging is accompanied by a gradual deterioration in multiple cognitive abilities and brain structures. Both cognitive function and white matter (WM) structure are found to be associated with neurodegeneration diseases and correlated with sex during aging. However, it is still unclear whether the brain structural change could be attributable to sex, and how sex would affect cognitive performances during aging. Materials and Methods: Diffusion magnetic resonance imaging (MRI) scans were performed on 1127 healthy participants (age range: 21-89) at a single site. The age trajectories of the WM tract microstructure were delineated to estimate the turning age and changing rate between sexes. The canonical correlation analysis and moderated mediation analysis were used to examine the relationship between sex-linked WM tracts and cognitive performances. Results: The axon intactness and demyelination of sex-linked tracts during aging were multifaceted. Sex-linked tracts in females peak around 5 years later than those in males but change significantly faster after the turning age. Projection and association tracts (e.g., corticospinal tracts and parahippocampal cingulum) contributed to a significant decrease in visuospatial functions (VS) and executive functions (E). We discovered that there is a stronger indirect effect of sex-linked tracts on cognitive functions in females than in males. Conclusion: Our findings suggest that the vulnerable projection and association tracts in females may induce negative impacts on integrating multiple functions, which results in a faster decrease in VS and E. Impact statement By recruiting a healthy population for diffusion magnetic resonance imaging (MRI) scan, we demonstrated that the age-related changes of white matter (WM) integrity were manipulated by sex. Sex-linked tracts in females reached the turning age 5 years later, but change faster than those in males after the turning age. The most significant sex effect was found in projection and association tracts. Our results indicated that sex affected both WM microstructure and cognitive functions and was further involved in the mediation of the age-WM-cognition relationship. The vulnerability of projection and association tracts in females may induce negative impacts on visuospatial and executive functions.

Studies have shown that the BH3-only domain Bad regulates brain development via the control of programmed cell death (PCD), but very few studies have addressed its effect on the molecular signaling of brain development in the system. In this work, we examined the novel role of zebrafish Bad in initial programmed cell death for brain morphogenesis through the priming of p53-mediated stress signaling. In a biological function study on the knockdown of Bad by morpholino oligonucleotides, at 24 h post-fertilization (hpf) Bad defects induced abnormal hindbrain development, as determined in a tissue section by means of HE staining which traced the damaged hindbrain. Then, genome-wide approaches for monitoring either the upregulation of apoptotic-related genes (11.8%) or the downregulation of brain development-related genes (29%) at the 24 hpf stage were implemented. The p53/caspase-8-mediated apoptotic death pathway was strongly involved, with the pathway being strongly reversed in a p53 mutant ( p53 M214K ) line during Bad knockdown. Furthermore, we propose the involvement of a p53-mediated stress signal which is correlated with regulating Bad loss-mediated brain defects. We found that some major genes in brain development, such as crybb1 , pva1b5 , irx4a , pax7a , and fabp7a , were dramatically restored in the p53 M214K line, and brain development recovered to return movement behavior to normal. Our findings suggest that Bad is required for (PCD) control, exerting a p53 stress signal on caspase-8/tBid-mediated death signaling and brain development-related gene regulation.

Xihuang pill, an approved Chinese medicine formula (state medical permit number. Z11020073), is a commonly used adjuvant drug for cancer patients in China. Xihuang pill has a satisfactory effect in treating breast cancer in clinics, especially triple-negative breast cancer (TNBC), which is the most aggressive type of breast cancer, and finite effective therapies. However, the mechanism of Xihuang pill in treating TNBC remains unclear. The present study aims to explore the pharmacological mechanism of Xihuang pill in treating advanced TNBC. We identified the main chemical components of Xihuang pill by using HPLC-Q-TOF-MS/MS. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) analysis shows that serum containing Xihuang pill (XS) had no obvious killing effect on any subtype of breast cancer cells, but it inhibited mammosphere colony formation of two TNBC cell lines (4T1 and HCC1806 cells) and could enhance the inhibitory effect of paclitaxel (PTX) on the proliferation of 4T1 and HCC1806 cells when combined with PTX. Seventy-six active compounds in Xihuang pill, their 300 protein targets, and 16667 TNBC stem cell-related genes were identified. The drug-herb-active compound-target gene-disease network and enrichment analyses were constructed with 190 overlapping candidate targets. Through text mining and molecular docking, the target gene NR3C2 and its active compound naringenin were selected for further validation. According to the TCGA database, we observed that a high expression of NR3C2 promoted a higher survival probability regarding overall survival (OS). In vitro experiments indicated that naringenin presented an identical effect to XS, possibly by regulating the NR3C2 expression. Overall, this study explored the effect of Xihuang pill in treating advanced TNBC cells and showed that naringenin, which is the key active compound of Xihuang pill, could lessen the stemness of TNBC cells to produce a synergistic effect on PTX by regulating the NR3C2 gene., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a past co-authorship with several of the authors HLZ, HDH., (Copyright © 2021 Zhang, Yang, Wu, Fang, Lu, Li, Li, Zuo, Ren, Liu, Xu, Wen, Huang, Hong and Chen.)

Engineering strong single-photon optomechanical couplings is crucial for optomechanical systems. Here, we propose a hybrid quantum system consisting of a nanobeam (phonons) coupled to a spin ensemble and a cavity (photons) to overcome it. Utilizing the critical property of the lower-branch polariton (LBP) formed by the ensemble-phonon interaction, the LBP-cavity coupling can be greatly enhanced by three orders magnitude of the original one, while the upper-branch polariton (UBP)-cavity coupling is fully suppressed. Our proposal breaks through the condition of the coupling strength less than the critical value in previous schemes using two harmonic oscillators. Also, strong Kerr effect can be induced in our proposal. This shows our proposed approach can be used to study quantum nonlinear and nonclassical effects in weakly coupled optomechanical systems.

Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/tlcr-21-634). Dr. IJO has grant from Roche; he also has received consulting fee from Roche, Ono, MSD, Pfizer, Boehringer-Ingelheim, AstraZeneca and Takeda. Dr. YT reports grants from JSPS KAKENHI grant number JP18K15928 and grants from Takeda Science Foundation outside the submitted work. Dr. SW reports grant and personal fee from AstraZeneca and Boehringer Ingelheim, personal fee from Chugai Pharma, Ono Pharmaceutical, Bristol-Myers, Eli Lilly, MSD, Taiho Pharmaceutical, Pfizer, Novartis, Daiichi Sankyo. Dr. RC has received consulting fees, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AZ, MSD, BMS, Roche, TAKEDA, Pfizer, janssen, Bayer, Novartis; Dr. RC has Participation on a Data Safety Monitoring Board or Advisory Board with AZ, MSD, BMS, Roche, TAKEDA, Pfizer, janssen, Bayer, Novartis; Dr. RC has received Support for attending meetings and/or travel from Roche, MSD, Takeda; Dr. RC declares stock ownership with The christie private care. Dr. KM reports medical education grant, Africa from Varian and Pfizer, Clinical trial grant from AstraZeneca and Novartis; travel and accommodations to a clinical trial meeting, 2019 from AstraZeneca; Dr. KM is an unpaid Board of Directors of Global Access to Cancer Care Foundation. Dr. JCS has grant support from National Institute of Health and the Noah’s Hope Foundation; she also has a family member that owns stock options and receives financial compensation from Vida Diagnostics. Dr. MF participated in advisory board for Astrazeneca, AbbVie and Beigene LLC. Dr. DDR reports grants from Bristol-Myers Squibb, grants from AstraZeneca, grants from Boehringer Ingelheim, from Philips, from Olink, from Celgene, from Seattle Genetics, from Roche/Genentech, from Merck/Pfizer, outside the submitted work. Dr. FC reports fees for membership of an advisory board from Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, Pharmamar, Novocure and MSD. Dr NS obtained commercial research grants from Eli Lilly, Chugai Pharmaceutical, Taiho Pharmaceutical, Pfizer Japan, Ono Pharmaceutical, and Nippon Boehringer Ingelheim, and has received speaking honoraria from Eli Lilly, AstraZeneca, MSD Oncology, Chugai Pharmaceutical, Taiho Pharmaceutical, Pfizer Japan, Ono Pharmaceutical, Nippon Boehringer Ingelheim, and Bristol-Myers Squibb Japan. TH serves as an unpaid editorial board member of Translational Lung Cancer Research from Jan 2020 to Dec 2021. FC serves as an unpaid editorial board member of Translational Lung Cancer Research from Aug 2021 to Jul 2023. MF serves as an unpaid editorial board member of Translational Lung Cancer Research from Sep 2019 to Sep 2021. SY serves as an unpaid editorial board member of Translational Lung Cancer Research from Sep 2019 to Sep 2021. GM serves as an unpaid editorial board member of Translational Lung Cancer Research from Aug 2021 to Jul 2023. PH serves as an unpaid editorial board member of Translational Lung Cancer Research from Mar 2021 to Feb 2023. The other authors have no conflicts of interest to declare.

The large scale lignocellulosic biomass wastes could also be regarded as abundantly-available renewable resources, and how to convert them into value-added products via sustainable approaches is still a big challenge. In this work, we demonstrated a facile pyrolysis method to construct N, P-dually doped biochar materials from the lignocellulosic biomass wastes. The as-synthesized N, P-dually doped biochar samples could act as electrocatalysts for oxygen reduction and evolution reactions (ORR/OER), showing excellent catalytic performance and long-term durability, as well as robust tolerance to CO and methanol. The unique hierarchical porous structure, favorable electronic structure modified by the N and P doping, as well as a variety of defect sites induced by the N and P doping into the carbon framework were identified as the main contributions to the prominent catalytic activity of the as-synthesized N, P-dually doped biochar materials. We expect this work would spur more efforts into developing advanced materials from the large scale lignocellulosic biomass wastes., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Family physicians play an essential role as gatekeepers in primary health care. However, most studies in the past focused on the geographic maldistribution of family physicians, and few studies focused on the distribution of family physicians between private practices and hospitals. This study aims to analyze the trends in practice locations of family physicians in Taiwan between 1999 and 2018, using the databases of the Taiwan Association of Family Medicine and Taiwan Medical Association. Although the annual number of physicians registered as family physicians had steadily increased from 1876 in 1999 to 3655 in 2018, the ratio of family physicians practicing in hospitals to total family physicians remained stable around 40% in the study period. Even after eliminating the trainees who were entirely registered at hospitals, the proportion of hospital-based family physicians still accounted for about one-third of the total in each year. In conclusion, family physicians had been continuously demanded by hospitals in Taiwan. If the supply of primary care-oriented family physicians is insufficient outside hospitals, health manpower planning would require urgent adjustments.

Background: The frail elderly are prone to falls and fractures, which can result in dependency, disability, admission to institutions, and even death. They are at increased risk of frailty due to decreased physical activity, cognitive decline, and depression. Some evidence suggests that music therapy with physical activities may be particularly beneficial., Objective: This study aimed to investigate the intervention effect of music therapy with physical activities (MTPA) on frail elderly in the community., Methods: A quasi-experimental design was adopted. We selected 10 community care centers in southern Taiwan, in which elderly people over the age of 65 were assigned to a MTPA group and a comparison group after obtaining their informed consent. The MTPA group performed group music activities once a week for 120 min for 12 weeks, while the comparison group only continued with their daily activities. Instruments in this study included the Kihon Checklist, Senior Fitness Test (with Body Mass Index (BMI) and seven physical fitness items), Mini-Mental Status Examination (MMSE), and Geriatric Depression Scale Short Form (GDS-SF)., Results: A total of 132 community elders agreed to participate in this study, and 122 completed both the pretest and posttest, with 62 in the music therapy group and 60 in the comparison group. The results of ANCOVA showed that after intervention, except for BMI, the Kihon frailty assessment, seven fitness scores individually and in total, MMSE, and depression showed significant improvements in the music therapy group relative to the comparison group (all p < 0.05)., Conclusion: MTPA can improve the frailty index, cognitive function, depression, and physical fitness index in the community elderly. The results of this study can be used as a reference for the design of activities for the community elderly, to provide them with appropriate activities, improve their physical functions, and improve or delay their disability.

Objective: To understand the current status of foreign dual-degree programs of Medical Doctor (MD) and Master of Public Health (MPH) and provide evidence-based decision-making reference for promoting the education of high-level applied public health talents in China. Methods: The list of involved institutions and information of foreign MD-MPH dual-degree programs was collected through literature retrieval, online information searching, and additional survey of key figures. We extracted the details of each project regarding professional fields, core competence, length of schooling, teaching and learning arrangement, internship eligibility, and graduation assessment. Python 3.8.0 was used for data cleaning, and the occurrence frequency of related items in each dimension was calculated. Results: A total of 99 MD-MPH programs from 104 foreign institutions were included, among which 97.1% of them were implemented in universities from the United States. The School of Public Health provided 42.4% (42/99) of the programs. Epidemiology was the major discipline set up among most programs, accounting for 12.0% (29/241) of all the specialties involved. Epidemiological research methods, health policy management and practice, and public health practice were the top 3 core competencies to be mastered. Of the 99 programs, 87 gave information on the length of the program, of which 74.7% (65/87) were five years, 6.9% (6/87) were four years, and 18.4% (16/87) included both 4-year and 5-year programs. Conclusions: The international MD-MPH programs were sophisticated and mainly organized by the School of Public Health alone or in conjunction with the School of Medicine. Epidemiology is the core course and competence objective, with a length of 4-5 years. Through learning experience from international MD-MPH programs and the Chinese unique medical development background, China should optimize its medical education system to develop a suitable talent training strategy for MD-MPH dual-degree programs in the new era.

In addition to the receptor-binding domain (DII), the C-terminal domain (DIII) of three-domain Cry insecticidal δ-endotoxins from Bacillus thuringiensis has been implicated in target insect specificity, yet its precise mechanistic role remains unclear. Here, the 21 kDa high-purity isolated DIII fragment derived from the Cry4Ba mosquito-specific toxin was achieved via optimized preparative FPLC, allowing direct rendering analyses for binding characteristics toward its target receptor- Aedes aegypti membrane-bound alkaline phosphatase (Aa-mALP). Binding analysis via dotblotting revealed that the Cry4Ba-DIII truncate was capable of specific binding to nitrocellulose-bound Aa-mALP, with a binding signal comparable to its 65 kDa Cry4Ba-R203Q full-length toxin. Further determination of binding affinity via sandwich ELISA revealed that Cry4Ba-DIII exhibited a rather weak binding to Aa-mALP with a dissociation constant ( K d ) of ≈1.1 × 10 -7 M as compared with the full-length toxin. Intermolecular docking between the Cry4Ba-R203Q active toxin and Aa-mALP suggested that four Cry4Ba-DIII residues, i.e., Glu 522 , Asn 552 , Asn 576 , and Leu 615 , are potentially involved in such toxin-receptor interactions. Ala substitutions of each residue (E522A, N552A, N576A and L615A) revealed that only the L615A mutant displayed a drastic decrease in biotoxicity against A. aegypti larvae. Additional binding analysis revealed that the L615A-impaired toxin also exhibited a reduction in binding capability to the surface-immobilized Aa-mALP receptor, while two bio-inactive DII-mutant toxins, Y332A and F364A, which almost entirely lost their biotoxicity, apparently retained a higher degree of binding activity. Altogether, our data disclose a functional importance of the C-terminal domain of Cry4Ba for serving as a potential receptor-binding moiety in which DIII-Leu 615 could conceivably be exploited for the binding to Aa-mALP, highlighting its contribution to toxin interactions with such a target receptor in mediating larval toxicity.

The application of day surgery on thoracic surgery is just started, and the innovation of surgical robots and their application on thoracic surgery bring new opportunities to the development of thoracic day surgery. However, the clinical practice of robot-assisted thoracic day surgery (RTDS) in China still has challenges and disagreements. Based on the experience of domestic experts in the field of RTDS clinical practice, this review discussed several key points of RTDS, including the future direction of RTDS, adjusting the indications according to their own conditions for the institutions carrying out RTDS, the robot-assisted advantage of RTDS being brought into play during the operation, and the perfect post-discharge follow-up mechanism being an important guarantee for the safe development of RTDS, to promote the application progress of RTDS in China.

Background: Drug-resistant tuberculosis (DR-TB), diabetes and exposure to air pollution are thought to be important threat to human health, but no studies have explored the effects of ambient air pollutants on DR-TB when adjusting diabetes status so far., Methods: We performed a study among 3759 newly diagnosed TB cases with drug-susceptibility testing results, diabetes status, and individual air pollution data in Shandong from 2015 to 2019. Generalized linear mixed models (GLMM) including three models (Model 1: without covariates, Model 2: adjusted by diabetes status only, Model 3: with all covariates) were applied., Results: Of 3759 TB patients enrolled, 716 (19.05%) were DR-TB, and 333 (8.86%) had diabetes. High exposure to O 3 was associated with an increased risk of RFP-resistance (Model 2 or 3: odds ratio (OR) = 1.008, 95% confidence intervals (CI): 1.002-1.014), ethambutol-resistance (Model 3: OR = 1.015, 95%CI: 1.004-1.027) and any rifampicin+streptomycin resistance (Model 1,2,3: OR = 1.01, 95%CI: 1.002-1.018) at 90 days. In contrast, NO 2 was associated with a reduced risk of DR-TB (Model 3: OR = 0.99, 95%CI: 0.981-0.999) and multidrug-resistant TB (MDR-TB) (Model 3: OR = 0.977, 95%CI: 0.96-0.994) at 360 days. Additionally, SO 2 (Model 1, 2, 3: OR = 0.987, 95%CI: 0.977-0.998) showed a protective effect on MDR-TB at 90 days. PM 2.5 (90 days, Model 2: OR = 0.991, 95%CI: 0.983-0.999), PM 10 (360 days, Model 2: OR = 0.992, 95%CI: 0.985-0.999) had protective effects on any RFP+SM resistance., Conclusions: O 3 contributed to an elevated risk of TB resistance but PM 2.5 , PM 10 , SO 2 , NO 2 showed an inverse effect. Air pollutants may affect the development of drug resistance among TB cases by adjusting the status of diabetes., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

The hepatitis C virus (HCV), an obligatory intracellular pathogen, highly depends on its host cells to propagate successfully. The HCV life cycle can be simply divided into several stages including viral entry, protein translation, RNA replication, viral assembly and release. Hundreds of cellular factors involved in the HCV life cycle have been identified over more than thirty years of research. Characterization of these cellular factors has provided extensive insight into HCV replication strategies. Some of these cellular factors are targets for anti-HCV therapies. In this review, we summarize the well-characterized and recently identified cellular factors functioning at each stage of the HCV life cycle., Competing Interests: Conflict-of-interest statement: No conflict-of-interest is declared., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

The Crab Nebula is a bright source of gamma rays powered by the Crab Pulsar's rotational energy through the formation and termination of a relativistic electron-positron wind. We report the detection of gamma rays from this source with energies from 5 × 10 -4 to 1.1 peta-electron volts with a spectrum showing gradual steepening over three energy decades. The ultrahigh-energy photons imply the presence of a peta-electron volt electron accelerator (a pevatron) in the nebula, with an acceleration rate exceeding 15% of the theoretical limit. We constrain the pevatron's size between 0.025 and 0.1 parsecs and the magnetic field to ≈110 microgauss. The production rate of peta-electron volt electrons, 2.5 × 10 36 ergs per second, constitutes 0.5% of the pulsar spin-down luminosity, although we cannot exclude a contribution of peta-electron volt protons to the production of the highest-energy gamma rays., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Family medicine physicians have been on the front lines of the novel coronavirus disease 2019 (COVID-19) pandemic; however, research and publications in family medicine journals are rarely discussed. In this study, a bibliometric analysis was conducted on COVID-19-related articles published in PubMed-indexed English language family medicine journals in 2020, which recorded the publication date and author's country and collected citations from Google Scholar. Additionally, we used LitCovid (an open database of COVID-19 literature from PubMed) to determine the content categories of each article and total number of global publications. We found that 33 family medicine journals published 5107 articles in 2020, of which 409 (8.0%) were COVID-19-related articles. Among the article categories, 107 were original articles, accounting for only 26.2% of the articles. In terms of content, the main category was prevention, with 177 articles, accounting for 43.3% of the articles. At the beginning of the epidemic, 10 articles were published in family medicine journals in January 2020, accounting for 11% of all COVID-19-related articles worldwide; however, this accounted for <0.5% of all disciplinary studies in the entire year. Therefore, family medicine journals indeed play a sentinel role, and the intensities and timeliness of COVID-19 publications deserve further investigation.

Traditional bladder volume measurement from B-mode (two-dimensional) ultrasound has been found to produce inaccurate results, and thus in this work we aim to improve the accuracy of measurement from B-mode ultrasound. A total of 75 electronic medical records including ultrasonic images were reviewed retrospectively from 64 patients. We put forward a novel bladder volume measurement method, in which a three-dimensional (3D) reconstruction model was established from conventional two-dimensional (2D) ultrasonic images to estimate the bladder volume. The differences and relationships were analyzed among the actual volume, the traditional estimated volume, and the new reconstruction model estimated volume. We also compared the data in different volume groups from small volume to high volume. The mean actual volume is 531.8 mL and the standard deviation is 268.7 mL; the mean percentage error of traditional estimation is -28%. In our new bladder measurement method, the mean percentage error is -10.18% (N = 2), -4.72% (N = 3), -0.33% (N = 4), and 2.58% (N = 5). There is no significant difference between the actual volume and our new bladder measurement method (N = 4) in all data or the divided four groups. The estimated volumes from the traditional method or our new method are highly correlated with the actual volume. Our data show that the three-dimensional bladder reconstruction model provides an accurate measurement from conventional B-mode ultrasonic images compared with the traditional method. The accuracy is seen across different groups of volume, and thus we can conclude that this is a reliable and economical volume measurement model that can be applied in general software or in apps on mobile devices.

Uranium (U) geochemistry and its isotopic compositions of reservoir sediments in U mine area were poorly understood. Herein, U and Th isotopic compositions were employed to investigate source apportionment and geochemical behavior of U in 41 reservoir sediments from a U mining area, Guangdong, China. The remarkably high contents of both total U (207.3-1117.7 mg/kg) and acid-leachable U (90.3-638.5 mg/kg) in the sediments exhibit a severe U contamination and mobilization-release risk. The U/Th activity ratios (ARs) indicate that all sediments have been contaminated apparently by U as a result of discharge of U containing wastewater, especially uranium mill tailings (UMT) leachate, while the variations of U/Th ARs are dominated by U geochemical behaviors (mainly redox process and adsorption). The U isotopic compositions (δ 238 U) showed a large variance through the sediment profile, varying from - 0.62 to - 0.04‰. The relation between δ 238 U and acid-leachable U fraction demonstrates that the U isotopic fractionation in sediments can be controlled by bedrock weathering (natural activity), UMT leachate (anthropogenic activity) and subsequent biogeochemical processes. The findings suggest that U-Th isotopes are a powerful tool to better understand U geochemical processes and enrichment mechanism in sediments that were affected by combined sources and driving forces., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The COVID-19 pandemic was caused by SARS-CoV-2 infection. To prevent the spread of SARS-CoV-2, an effective vaccine is required. Two linear peptides from potential B-cell epitopes in the spike protein of SARS-CoV-2 (a.a. 440-460; a.a. 494-506) were synthesized and used to immunize rabbits. High-titer antibodies of IgG were produced, purified, and verified by Western blot analysis. Antibodies against these two epitopes could effectively neutralize SARS-CoV-2 pseudoviral particles with the spike proteins from not only the original strain (basal; wild-type), but also a strain with a single point mutation (D614G), and two other emerging variants (the Alpha and Beta variants) prevalent around the world, but not from SARS-CoV. In conclusion, antibodies against these two epitopes are protective. This information is important for the development of vaccines against SARS-CoV-2.

A visible-light-induced decarboxylation reaction was developed for the synthesis of alkylated benzimidazo[2,1- a ]isoquinoline-6(5 H )-ones and indolo[2,1- a ]isoquinolin-6(5 H )-ones under metal-free conditions. Impressively, metal catalysts and traditionally volatile organic solvents could be effectively avoided.

Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare.

Background: This study aimed to assess the use of medical record items in clinical research in one large academic medical center in Taiwan., Methods: A descriptive survey design was adopted to collect the data. Articles published in 2018 by Taipei Veterans General Hospital (TVGH) staff as the first author were obtained. The types of specialties and types of research were analyzed. To understand the conditions for the use of medical records, the retrospective research using hospital's medical records were analyzed. Each article was read in entirety to realize the use and number of patients and the medical record items., Results: Among the 362 articles first-authored by TVGH staff in 2018, 219 (60.4%) were classified as clinical studies, 60 (16.6%) as basic studies, 53 (14.6%) as database studies, and 30 (8.2%) as other categories. About 50% of the retrospective research using TVGH medical records had a case number <100 (67 cases, 49.6%) with an average number of 41 cases and 13 studies (9.6%) had a case number >1000. Analysis of the number of medical record items used in 135 retrospective research studies based on TVGH medical records showed that 118 (87.4%) used basic patient information. In addition to basic information, notes written by professionals were used most frequently (73 cases, 54.0%), whereas medication information was used in 50 cases (37.0%); laboratory test data were used in 49 cases (36.2%); and body measurements was used in 27 cases (20%)., Conclusion: More than one-third of publications utilized medical records, but the patient numbers and record items in use were relatively limited. In the era of digitalization and big data analytics, the potential of medical records in research deserves attention. Investment in establishing a more accessible database of medical records to access nonstructural, descriptive medical records could be considered., Competing Interests: Conflicts of interest: Dr. Tzeng-Ji Chen, Dr. Shih-Hwa Chiou and Dr. Shinn-Jang Hwang, Editorial board members at Journal of the Chinese Medical Association, have no roles in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2021, the Chinese Medical Association.)

Background: Following endotracheal intubation, clearing secretions above the endotracheal tube cuff decreases the incidence of ventilator-associated pneumonia (VAP); therefore, subglottic secretion drainage (SSD) is widely advocated. Our group developed a novel technique to remove the subglottic secretions, the rapid-flow expulsion maneuver (RFEM). The objective of this study was to explore the effectiveness and safety of RFEM compared with SSD., Methods: This study was a single-center, prospective, randomized and controlled trial, conducted at Respiratory Intensive Care Unit (ICU) of Beijing Chao-Yang Hospital, a university-affiliated tertiary hospital. The primary outcome was the incidence of VAP, assessed for non-inferiority., Results: Patients with an endotracheal tube allowing drainage of subglottic secretions (n = 241) were randomly assigned to either the RFEM group (n = 120) or SSD group (n = 121). Eleven patients (9.17%) in the RFEM group and 13 (10.74%) in the SSD group developed VAP (difference, - 1.59; 95% confidence interval [CI] [- 9.20 6.03]), as the upper limit of 95% CI was not greater than the pre-defined non-inferiority limit (10%), RFEM was declared non-inferior to SSD. There were no statistically significant differences in the duration of mechanical ventilation, ICU mortality, or ICU length of stay and costs between groups. In terms of safety, no accidental extubation or maneuver-related barotrauma occurred in the RFEM group. The incidence of post-extubation laryngeal edema and reintubation was similar in both groups., Conclusions: RFEM is effective and safe, with non-inferiority compared to SSD in terms of the incidence of VAP. RFEM could be an alternative method in first-line treatment of respiratory ICU patients. Trial registration This study has been registered on ClinicalTrials.gov (Registration Number: NCT02032849, https://clinicaltrials.gov/ct2/show/NCT02032849 ); registered on January 2014.

We report the discovery of an extended very-high-energy (VHE) gamma-ray source around the location of the middle-aged (207.8 kyr) pulsar PSR J0622+3749 with the Large High-Altitude Air Shower Observatory (LHAASO). The source is detected with a significance of 8.2σ for E>25  TeV assuming a Gaussian template. The best-fit location is (right ascension, declination) =(95.47°±0.11°,37.92°±0.09°), and the extension is 0.40°±0.07°. The energy spectrum can be described by a power-law spectrum with an index of -2.92±0.17&#95;{stat}±0.02&#95;{sys}. No clear extended multiwavelength counterpart of the LHAASO source has been found from the radio to sub-TeV bands. The LHAASO observations are consistent with the scenario that VHE electrons escaped from the pulsar, diffused in the interstellar medium, and scattered the interstellar radiation field. If interpreted as the pulsar halo scenario, the diffusion coefficient, inferred for electrons with median energies of ∼160  TeV, is consistent with those obtained from the extended halos around Geminga and Monogem and much smaller than that derived from cosmic ray secondaries. The LHAASO discovery of this source thus likely enriches the class of so-called pulsar halos and confirms that high-energy particles generally diffuse very slowly in the disturbed medium around pulsars.

Objective: This study was designed to identify the risk factors for drug-resistant tuberculosis (DR-TB) and the association between comorbidity and drug resistance among retreated pulmonary tuberculosis (PTB)., Design: A retrospective study was conducted among all the 36 monitoring sites in Shandong, China, over a 16-year period. Baseline characteristics were collected from the TB Surveillance System. Categorical variables were compared by Fisher's exact or Pearson's χ 2 test. The risk factors for drug resistance were identified using univariable analysis and multivariable logistic models. The influence of comorbidity on different types of drug resistance was evaluated by performing multivariable logistic models with the covariates adjusted by age, sex, body mass index, drinking/smoking history and cavity., Results: A total of 10 975 patients with PTB were recorded during 2004-2019, and of these 1924 retreated PTB were finally included. Among retreated PTB, 26.2% were DR-TB and 12.5% had comorbidity. Smoking (adjusted OR (aOR): 1.69, 95% CI 1.19 to 2.39), cavity (aOR: 1.55, 95% CI 1.22 to 1.97) and comorbidity (aOR: 1.44, 95% CI 1.02 to 2.02) were risk factors for DR-TB. Of 504 DR-TB, 9.5% had diabetes mellitus, followed by hypertension (2.0%) and chronic obstructive pulmonary disease (1.8%). Patients with retreated PTB with comorbidity were more likely to be older, have more bad habits (smoking, alcohol abuse) and have clinical symptoms (expectoration, haemoptysis, weight loss). Comorbidity was significantly associated with DR-TB (aOR: 1.44, 95% CI 1.02 to 2.02), overall rifampin resistance (aOR: 2.17, 95% CI 1.41 to 3.36), overall streptomycin resistance (aOR: 1.51, 95% CI 1.00 to 2.27) and multidrug resistance (aOR: 1.96, 95% CI 1.17 to 3.27) compared with pan-susceptible patients (p<0.05)., Conclusion: Smoking, cavity and comorbidity lead to an increased risk of drug resistance among retreated PTB. Strategies to improve the host's health, including smoking cessation, screening and treatment of comorbidity, might contribute to the control of tuberculosis, especially DR-TB, in China., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

To improve the bioactivity of titanium alloy (Ti-6Al-4V), CaO-SiO 2 coatings on titanium alloys were fabricated using laser cladding method. The effect of Na 2 O and ZnO on the microstructure and properties of the prepared coatings was discussed. The microstructure of the CaO-SiO 2 coatings consists of cellular grains and cellular dendrites. The mutual diffusion of elements occurs between the coating and substrate. The base CaO-SiO 2 coating is composed of different phases including CaTiO 3 , α-Ca 2 (SiO 4 ), SiO 2 , TiO 2 and CaO. The formation of CaTiO 3 in the ceramic layer was analyzed through thermodynamics. Na 2 O has little influence on the microstructure, average hardness and wear resistance. When ZnO is added to the precursor, the microstructure turns to cell dendrite, and ZnO and Zn 2 SiO 4 appear in the corresponding coating. The addition of ZnO reduces the average hardness and wear resistance of the ceramic layer. The in vitro soaking in SBF shows that the laser cladding coating has the ability to form an apatite layer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To analyze the level of the knowledge and related factors of cancer prevention and treatment among residents of Beijing in 2020. Methods: From April 14 to 21,a total of 11 721 residents were recruited in the study by using anonymous network sampling method. A WeChat online electronic questionnaires was conducted to collect basic demographic characteristics and the knowledge of cancer prevention and treatment. The Chi-square test was used to compare the difference of the level of the cancer prevention and treatment knowledge among different groups. A multivariate linear regression model was used to analyze the related factors. Results: Among the subjects, 72.9% (8 542) were male and 93.7% (10 983) were urban residents. The total number of questions answered by the subjects was 117 210 of which 89 093 were known, and the overall awareness rate among the residents was 76.0%. The female, aural residents, with junior college education, and worked in government institutions had a good performance of the knowledge ( P< 0.05), about 83.4%, 79.7%, 82.3% and 82.0% respectively. The results of multivariate linear regression model showed that female[β=0.798(95 %CI :0.702,0.894)] and junior college education[β=3.271(95 %CI :2.993,3.609)] could know more questions compared to male and primary school education ( P< 0.05); compared with working in the government institutions, agricultural laborer[β=-0.911(95 %CI :-1.057,-0.766)], retired personnel[β=-2.273(95 %CI :-2.532,-2.014)], school students[β=-0.629(95 %CI :-0.796,-0.462)] and other occupation people[β=-0.376(95 %CI :-0.634,-0.119)] could know fewer questions ( P< 0.05). Conclusion: The level of the cancer prevention and treatment knowledge among residents in Beijing was relatively high. Gender, education level and occupation were relevant factors.

The clustered regularly interspaced short palindromic repeats (CRISPR) technology has been widely applied for nucleic acid detection because of its high specificity. By using the highly specific and irreversible bond between HaloTag and its alkane chlorine ligand, we modified dCas9 (deactivated CRISPR/Cas9) with biotin as a biosensor to detect nucleic acids. The CRISPR biosensor was facilely prepared to adequately maintain its DNA-recognition capability. Furthermore, by coupling biolayer interferometry (BLI) with the CRISPR biosensor, a real-time, sensitive, and rapid digital system called CRISPR-BLI was established for the detection of double-stranded DNA. The CRISPR biosensor immobilised on the biolayer could recruit the target DNA onto the biosensor surface and change its optical thickness, resulting in a shift in the interference pattern and responding signal of the BLI. The CRISPR-BLI system was further applied to detect the ALP gene of Escherichia coli DH5α combined with a polymerase chain reaction, which demonstrated a linear range from 20 to 20 000 pg and a low detection limit (1.34 pg). The CRISPR-BLI system is a promising approach for rapid and sensitive detection of target DNA analytes., (© 2021 Wiley-VCH GmbH.)

Background: Considering the high morbidity and mortality of lung cancer and the high incidence of pulmonary nodules, clearly distinguishing benign from malignant lung nodules at an early stage is of great significance. However, determining the kind of lung nodule which is more prone to lung cancer remains a problem worldwide., Methods: A total of 480 patients with pulmonary nodule data were collected from Shandong, China. We assessed the clinical characteristics and computed tomography (CT) imaging features among pulmonary nodules in patients who had undergone video-assisted thoracoscopic surgery (VATS) lobectomy from 2013 to 2018. Preliminary selection of features was based on a statistical analysis using SPSS. We used WEKA to assess the machine learning models using its multiple algorithms and selected the best decision tree model using its optimization algorithm., Results: The combination of decision tree and logistics regression optimized the decision tree without affecting its AUC. The decision tree structure showed that lobulation was the most important feature, followed by spiculation, vessel convergence sign, nodule type, satellite nodule, nodule size and age of patient., Conclusions: Our study shows that decision tree analyses can be applied to screen individuals for early lung cancer with CT. Our decision tree provides a new way to help clinicians establish a logical diagnosis by a stepwise progression method, but still needs to be validated for prospective trials in a larger patient population., (© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

The extension of the cosmic-ray spectrum beyond 1 petaelectronvolt (PeV; 10 15 electronvolts) indicates the existence of the so-called PeVatrons-cosmic-ray factories that accelerate particles to PeV energies. We need to locate and identify such objects to find the origin of Galactic cosmic rays 1 . The principal signature of both electron and proton PeVatrons is ultrahigh-energy (exceeding 100 TeV) γ radiation. Evidence of the presence of a proton PeVatron has been found in the Galactic Centre, according to the detection of a hard-spectrum radiation extending to 0.04 PeV (ref. 2 ). Although γ-rays with energies slightly higher than 0.1 PeV have been reported from a few objects in the Galactic plane 3-6 , unbiased identification and in-depth exploration of PeVatrons requires detection of γ-rays with energies well above 0.1 PeV. Here we report the detection of more than 530 photons at energies above 100 teraelectronvolts and up to 1.4 PeV from 12 ultrahigh-energy γ-ray sources with a statistical significance greater than seven standard deviations. Despite having several potential counterparts in their proximity, including pulsar wind nebulae, supernova remnants and star-forming regions, the PeVatrons responsible for the ultrahigh-energy γ-rays have not yet been firmly localized and identified (except for the Crab Nebula), leaving open the origin of these extreme accelerators.

One proposed toxic mechanism of Bacillus thuringiensis Cry δ-endotoxins involves pore formation in target membranes by the α4-α5 transmembrane hairpin constituting their pore-forming domain. Here, nine selected charged and uncharged polar residues in the pore-lining α4 of the Cry4Aa mosquito-active toxin were substituted with Ala. All mutant toxins, i.e., D169A, R171A, Q173A, H178A, Y179A, H180A, Q182A, N183A and E187A, were over-expressed in Escherichia coli as 130-kDa protoxin inclusions at levels comparable to the wild-type toxin. Bioassays against Aedes aegypti larvae revealed that only H178A and H180A mutants displayed a drastic reduction in biotoxicity, albeit almost complete insolubility observed for H178A, but not for H180A inclusions. Further mutagenic analysis showed that replacements of His 180 with charged (Arg, Lys, Asp, Glu), small uncharged polar (Ser, Cys) or small non-polar (Gly, Val) residues severely impaired the biotoxicity, unlike substitutions with relatively large uncharged (Asn, Gln, Leu) or aromatic (Phe, Tyr, Trp) residues. Similar to the trypsin-activated wild-type toxin, both bio-active and -inactive H180 mutants were still capable of releasing entrapped calcein from lipid vesicles and producing cation-selective channels with ~130-pS maximum conductance. Analysis of the Cry4Aa structure revealed the existence of a hydrophobic cavity near the critical His 180 side-chain. Analysis of simulated structures revealed that His 180 -to-smaller residue conversions create a gap disrupting such cavity's hydrophobicity and hence structural arrangements of the α4-α5 hairpin. Altogether, our data disclose a critical involvement in Cry4Aa-biotoxicity of His 180 exclusively present in the lumen-facing α4 for providing proper environment for the α4-α5 hairpin prior to membrane-inserted pore formation., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background and Aim: The role of hypoxia-inducible factor-1α (HIF-1α) and hypoxia-inducible factor-2α (HIF-2α) has been implicated in the clinical prognosis of hepatocellular carcinoma (HCC), but the results remain controversial. We aim to investigate the association of HIF-1α and HIF-2α overexpression with the prognosis and clinicopathological features of HCC., Methods: A systematic search was conducted in PubMed, Embase, Scopus, Web of Science, and Cochrane Library until June 20, 2020. Meta-analysis was conducted to generate combined HRs with 95% confidence intervals (CI) for overall survival (OS) and disease-free survival (DFS). Odds ratios (ORs) with 95% CI were also derived by fixed or random effect model., Results: Twenty-two studies involving 3238 patients were included. Combined data suggested that overexpression of HIF-1α in HCC was not only correlated with poorer OS [HR = 1.75 (95% CI: 1.53-2.00)] and DFS [HR = 1.64 (95% CI: 1.34-2.00)] but was also positively associated with vascular invasion [OR = 1.83 (95% CI: 1.36-2.48)], tumor size [OR = 1.36 (95% CI: 1.12-1.66)], and tumor number [1.74 (95% CI: 1.34-2.25)]. In contrast, HIF-2α overexpression was not associated with the prognosis and clinicopathological features of HCC., Conclusion: Our data provided compelling evidence of a worse prognosis of HCC in HIF-1α overexpression patients but not HIF-2α overexpression ones., (© 2021 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)