Analysis of quadriceps strength and knee pain Among US Adults.

OBJECTIVE: To investigate the association of quadriceps strength with the presence of knee pain. DESIGN: This cross-sectional study was based on data from the 1999-2000 and 2001-2002 National Health and Nutrition Examination Survey. SETTING: This was a community-based study. PARTICIPANTS: This study included 2,619 adults with complete data for knee pain, quadriceps strength, and covariates. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Self-reported knee pain. RESULTS: This study included 2,619 individuals, 1,287 (52.66%) of whom were female and 1,543 (81.66%) identified as Mexican-American. The mean ± standard deviation age was 62.48 ± 9.71 years. After adjusting for covariates, the odds of knee pain decreased with every 20 N/m increase in quadriceps strength (odds ratio, 0.87; 95% CI, 0.81-0.94). Individuals in the upper quartile of quadriceps strength had lower odds of knee pain than those in the lower quartile (Q4 vs. Q1 [reference]: odds ratio, 0.28, 95% CI, 0.15-0.52; ptrend = 0.006). Non-linear analyses indicated L-shaped associations for knee pain. The subgroup analyses showed no significant interactions, except for sex (pinteraction = 0.046). The significance of the sex interaction indicated a correlation exclusively in females. CONCLUSIONS: The results demonstrated an inverse association between quadriceps strength and the presence of knee pain. The subgroup analysis by sex showed that this inverse relationship was statistically significant in the female but not in the male subgroup.

Exploring Protein Bioconjugation: A Redox-Based Strategy for Tryptophan Targeting.

Amino acid bioconjugation technology has emerged as a pivotal tool for linking small-molecule fragments with proteins, antibodies, and even cells. The study in Nature by Chang and Toste introduces a redox-based strategy for tryptophan bioconjugation, employing N-sulfonyloxaziridines as oxidative cyclization reagents, demonstrating high efficiency comparable to traditional click reactions. Meanwhile, this tool provides feasible methods for investigating the mechanisms underlying functional tryptophan-related biochemical processes, paving the way for protein function exploration, activity-based proteomics for functional amino acid identification and characterization, and even the design of covalent inhibitors.

Bioactive atropisomers: Unraveling design strategies and synthetic routes for drug discovery.

Atropisomerism, an expression of axial chirality caused by limited bond rotation, is a prominent aspect within the field of medicinal chemistry. It has been shown that atropisomers of a wide range of compounds, including established FDA-approved drugs and experimental molecules, display markedly different biological activities. The time-dependent reversal of chirality in atropisomers poses complexity and obstacles in the process of drug discovery and development. Nonetheless, recent progress in understanding atropisomerism and enhanced characterization methods have greatly assisted medicinal chemists in the effective development of atropisomeric drug molecules. This article provides a comprehensive review of their special design thoughts, synthetic routes, and biological activities, serving as a reference for the synthesis and biological evaluation of bioactive atropisomers in the future.

Palladium-catalyzed asymmetric [4+2] annulation of vinyl benzoxazinanones with pyrazolone 4,5-diones to access spirobenzoxazine frameworks.

Herein, a palladium-catalyzed general synthetic strategy to access an attractive and decorated set of chiral spiro derivatives of benzoxazine compounds is unveiled utilizing vinyl benzoxazinanones reacted with pyrazolone 4,5-diones, which extends the application of vinyl benzoxazinanones with ketones. This asymmetric catalytic [4+2] cycloaddition reaction demonstrates a broad substrate scope with functional group tolerance in yields of up to 76% and up to 96% ee. A facile scale-up and straightforward conversion to diversely substituted products verify the synthetic utility of this method.

The history, current situation and prospect of lacunar infarct / 中华神经科杂志

The modern concept of lacunar infarct is largely based on the meticulous postmortem work of Fisher from the 1950s to 1970s, which forms the basis of the"lacunar hypothesis". Along with the application of CT or MRI techniques and classification of ischemic stroke subtypes, the lacunar infarct was endowed with the profile of imaging diagnosis and stroke subtypes. Thus, the concept of lacunar infarct has far expanded the initial pathological meanings and the terminology and definitions for lacunar infarct vary widely. In this review, the historical pathological findings and the term evolution of lacunar infarct were systemically reviewed, with a focus toward future directions in the complex entity of lacunar infarct.

Pay attention to subsequent arterial ischemic events after intracerebral hemorrhage / 中华神经科杂志

Survivors of intracerebral hemorrhage (ICH) have significantly higher risks of both arterial ischemic events and recurrent ICH after the first event. This uncertainty leaves clinicians with dilemmas about the therapy strategies for the secondary prevention of major vascular events after ICH. Clinicians mainly focus on the prevention of hemorrhage recurrence but overlook the increased risk of ischemic disease after ICH in routine clinical practice. Secondary stroke prevention measures after ICH including antithrombotic and statin treatments remain challenging due to the lack of dedicated studies with strong evidence. Decision-making on stroke prevention requires algorithmic approaches based on the hemorrhagic and ischemic risk stratification. This article systematically reviews the current evidence for the prevention and management of subsequent arterial ischemic events after ICH, aiming to promote further attention and research to address the current controversies and knowledge gap on this topic.

From Virtue to Norm: Ethical Thinking on the Construction of Harmonious Doctor-patient Relationship / 中国医学伦理学

Virtue ethics and normative ethics are corresponding ethical concepts, and their collision and integration promote the development of ethical system. On the issue of doctor-patient relationship, from virtue to norm is the objective requirement of social transformation and development, and is also the inevitable choice to resolve doctor-patient conflicts and reshape doctor-patient relationships. In the new era, the construction of doctor-patient relationship faces ethical dilemma such as one-sided emphasis on doctors’ virtue cultivation, unclear ethical responsibilities between doctors and patients, and lack of trust and tolerance between doctors and patients. Therefore, it is necessary to strengthen the institutionalization of doctor ethics, clarify the ethical responsibilities of both doctors and patients, optimize the social ethical ecological environment, so as to realize the ethical reconstruction of doctor-patient relationship from virtue to norm.

Efficacy and safety of olaparib in adjuvant therapy of BRCA1/2 mutated HER2-negative breast cancer：a meta-analysis / 中国药房

OBJECTIVE To systematically evaluate the efficacy and safety of olaparib in adjuvant therapy of breast cancer susceptibility gene （BRCA） 1/2 mutated human epidermal growth factor receptor 2 （HER2）-negative breast cancer， and to provide evidence-based reference for clinical treatment. METHODS Retrieved from CNKI， VIP， Wanfang data， PubMed， ScienceDirect， the Cochrane Library and Embase databases， randomized controlled trials about adjuvant therapy of olaparib （trial group） versus adjuvant therapy of other drugs （control group） were collected. After literature screening and data extraction， meta-analysis， publication bias analysis and sensitivity analysis were performed by using RevMan5.4 software. RESULTS A total of 5 randomized controlled trials were included， with a total of 2 633 patients， including 1 495 cases in trial group and 1 174 cases in control group. Meta-analysis showed that in terms of efficacy， compared with control group， overall survival [HR＝1.02， 95%CI （1.01，1.03）， P＝0.000 8] and progression-free survival [HR＝1.78， 95%CI（1.46，2.17）， P＜0.000 01] were longer significantly in the trial group. In terms of safety， compared with the control group， the incidence of adverse drug reactions at any level in the trial group was higher [RR＝1.41， 95%CI （1.12， 1.78）， P＝0.004]， while there was no statistically significant difference in the incidence of adverse drug reactions above level 3 between the two groups [RR＝1.75， 95%CI （0.82， 3.74）， P＝0.15]. The results of publication bias indicated that the possibility of publication bias in this study was relatively low. The results of sensitivity analysis showed that the results obtained in this study were robust. CONCLUSIONS Compared with patients without adjuvant therapy of olaparib， adjuvant therapy of olaparib can prolong overall survival and progression-free survival of patients with BRCA1/2 mutated HER2-negative breast cancer，but the risk of adverse drug reactions is relatively high.

One-Step Synthesis of Hydropyrrolo[3,2-b]indoles via Cascade Reactions of Oxindole-Derived Nitrones with Allenoates.

Hydropyrrolo[2,3-b]indole is a privileged indoline motif, while its analogue, hydropyrrolo[3,2-b]indole, has been much less explored. Herein, we developed a cascade reaction of oxindole-derived nitrones with allenoates, providing straightforward access to the tetracyclic hydropyrrolo[3,2-b]indole scaffolds. Formation of multiple C-C/C-X bonds and cleavage could be achieved within one synthetic step using a simple catalyst (Gimeracil) under mild conditions. The reaction pathway may involve the generation of spiro-hydroazepinone as the key intermediate.

Inter-coffee-ring effects boost rapid and highly reliable SERS detection of TPhT on a light-confining structure.

Triphenyltin chloride (TPhT) is a widely applied toxic compound that poses a significant threat to humans and the environment. Surface-enhanced Raman spectroscopy (SERS), capable of non-destructive, rapid, and trace detection, is desirable to better evaluate its distribution and content. However, a sensitive method with simple measuring protocols which maintains excellent reproducibility remains challenging. Here, we proposed an inter-coffee-ring effect to accelerate the sampling and measuring process while maintaining highly reproducible results. Two overlapping coffee-rings are formed through sequenced drying of gold nanorod colloids and a gold nanorod TPhT mixture on a superhydrophobic light-confining structure. Both the gold nanorods and the TPhT are enriched in the overlapping region. The gold nanorods reordered in such an area under the inter-coffee-ring effect yielded vast numbers of consistent hotspots at the sub-2 nm level. Such consistency leads to excellent SERS performance under the light-confining effect induced by the nanoarray substrates. The detection limits of the probe molecule R6G reached 10-12 M, and TPhT reached 10-8 M while achieving excellent stability and reproducibility, and a linear regression coefficient above 0.99 was achieved for TPhT. Crucially, the visible nature of the inter-coffee-ring overlap enabled rapid measurements, thus providing robust support for detecting environmental pollutants.

Asymmetric [4 + 2] Annulation of Cyclobutenones and Pyrazolone 4,5-Diones: Access to Novel δ-Lactone-Fused Spiropyrazolones.

Although numerous chiral pyrazolones with a six-membered spirocyclic center at the C4 position have been developed, the asymmetric construction of six-membered oxa-spiropyrazolones is still a challenging task in organic synthesis. Herein, we describe the [4 + 2] annulation of cyclobutanones and pyrazoline-4,5-diones for the efficient synthesis of δ-lactone-fused spiropyrazolone derivatives with generally high yields and good enantioselectivities under mild conditions. The successful scale-up synthesis and further transformation of the final product highlight the practicality and reliability of this reaction.

Hygiene risks and management advices for "Room Escape" venues / 环境与职业医学

In recent years, the "Room Escape" industry in China is booming, and this real live game has become popular. However, health threatening events such as fire, trauma, coma, and lung infection in the game venues have been reported at home and abroad. If these venues are not supervised in time, there will be great potential public safety and health hazards. In this review, we summarized the hidden dangers of public safety and health in such venues, including fire and safety hazards, persistent stress state, indoor ventilation problems, risk of contagious infection, non-player characters’ health risk, special film effects of 4D cinemas, mosquito problems, light pollution and noise, and food safety. Meanwhile, health management recommendations for the game venues were proposed from the aspects of formulating health management standards, improving health security measures, and strengthening related health education to players, so as to improve the hygiene levels of such venues and protect players and staff from injuries or diseases.

Research progress of epigenetic regulation in the ossification of spinal ligaments / 中华骨科杂志

Ossification of the spinal ligaments (OSL) is characterized by the appearance of pathologic bone tissue within the spinal ligamentous tissue. OSL tends to occur in the cervical and thoracic segments with important cause of spinal stenosis. Compression of the spinal cord or nerve roots by ossified masses can lead to severe neurological dysfunction, which has a tremendous impact on the quality of life of patients. However, the exact etiology and pathogenesis of OSL are still unclear. Epigenetic regulation is widespread in organisms and refers to the appearance of heritable changes in gene expression without alteration in genomic DNA sequence. As an important form of biodiversity regulation, epigenetic regulation plays an important role in development of several diseases. Epigenetic regulation has multiple manifestations in OSL, including DNA methylation, histone modifications, and non-coding RNA regulation. Sequencing tools, such as gene microarrays, have revealed significant differences in DNA methylation profiles and non-coding RNA expression between ossified and normal spinal ligaments. These differences can cause abnormal expression of osteogenesis-related target genes through direct or indirect pathways, thus affecting the ossification process of spinal ligaments. In addition, interactions between these epigenetic regulatory mechanisms constitute a large and complex regulatory network. Consequently, an in-depth understanding of the role of different epigenetic regulatory mechanisms and the linkages between them in the initiation and progression stages of OSL is expected to provide a valuable reference for the clinical diagnosis and treatment of OSL-related diseases.

Design, synthesis, and biological evaluation of nitroisoxazole-containing spiro[pyrrolidin-oxindole] derivatives as novel glutathione peroxidase 4/mouse double minute 2 dual inhibitors that inhibit breast adenocarcinoma cell proliferation.

A series of highly active CF3-containing 3'-(nitroisoxazole)spiro[pyrrolidin-3,2'-oxindoles] were synthesized and found to be novel glutathione peroxidase 4 (GPX4)/mouse double minute 2 (MDM2) dual inhibitors. Bioactive spirooxindole and isoxazole skeletons were combined, and the resulting compounds exhibited strong activities against both targets. In particular, compound 3d displayed excellent activity in the suppression of MDM2-mediated degradation of p53, as well as levels of GPX4, in MCF-7 breast cancer cells. Moreover, 3d also exhibited inhibitory effects on MDM2 and GPX4 in MCF-7 xenograft model to trigger ferroptotic and apoptotic cell death in in vivo experiments, which was consistent with the results of in vitro experiments.

Stereoselective synthesis of trifluoroethyl 3,2'-spirooxindole γ-lactam through the organocatalytic cascade reaction of 3-((2,2,2-trifluoroethyl)amino)indolin-2-one.

Newly designed 3-((2,2,2-trifluoroethyl)amino)indolin-2-ones were used for the facile synthesis of chiral fluoroalkyl-containing 3,2'-spirooxindole γ-lactam products. The secondary amine-catalysed Michael/hemiaminalization cascade reaction of 3-((2,2,2-trifluoroethyl)amino)indolin-2-one with α,ß-unsaturated aldehydes followed by oxidation can easily produce the desired products in high yields (up to 86%) with excellent enantioselectivities (up to 99% ee) and diastereoselectivities (up to >95 : 5 dr).

Predictive value of vertebral trabecular and endplate Hounsfield Units on cage subsidence followed posterior lumbar interbody fusion / 中华骨科杂志

Objective:To explore the predictive value of vertebral trabecular and endplate HU values on cage subsidence after posterior lumbar interbody fusion (PLIF), hope to provide reference for surgical planning.Methods:All of 72 patients with lumbar disc herniation that underwent PLIF were retrospectively reviewed, who were divided into two groups according to the occurrence of cage subsidence at one-year follow up. Cage subsidence was defined as more than 4 mm subsidence into the vertebrae valuated by CT at one-year follow up. There were 18 patients enrolled into Subsidence group and 54 patients enrolled into N-Subsidence group. The lumbar lordosis, segmental lordosis, intervertebral height, off-bed time, hospital stay, complications, the trabecular and endplate HU values of upper instrumented vertebrae (UIV) and lower instrumented vertebrae (LIV) were compared between the two groups. ROC was used to explore the thresholds of HU values.Results:There were 14 patients presented cage subsidence into the L4, 4 patients presented cage subsidence into the L5. There was no significant difference in lumbar lordosis, segmental lordosis, intervertebral height, off-bed time, hospital stay, or complications between the two groups. Both UIV and LIV trabecular and endplate showed a lower HU value in Subsidence group than those in N-Subsidence group. The most appropriate thresholds of HU value were 146, 172, 307, 254 for trabecular of UIV, trabecular of LIV, lower endplate of UIV, and upper endplate of LIV, respectively.Conclusion:Vertebral trabecular and endplate HU values could effectively predict the cage subsidence after PLIF, patients should be completely informed the risk of cage subsidence and larger cage should be recommended if they presented HU values under the certain threshold.

Adapted Rhythmic Gymnastics Based on ICF-CY for Children with Low Function Autism Spectrum Disorder / 中国康复理论与实践

Objective:To study the effect of adapted rhythmic gymnastics based on International Classification of Functioning, Disability and Health-Children and Youth Version (ICF-CY) on the fundamental motor skill development for children with low function autism spectrum disorder (ASD). Methods:Three boys aged 7.2 to 8 years with low function ASD (IQ 47 to 53) participated in the exercise since September, 2019. Their activities and motor function were analyzed with ICF-CY to develop a 12-week rehabilitation exercise, including physical fitness, gymnastics skills content and game. They were assessed with ICF-CY based Questionnaire and gross motor of Peabody Developmental Motor Scales (PDMS-2) before and after training. Results:The qualifiers of body structure, body function, activity and participation improved somehow after training. The scores of gross motor skills of PDMS-2 improved. Conclusion:The adapted rhythmic gymnastics training based on ICF-CY may improve the functioning, especially motor function, for children with low function ASD, which can be a kind of rehabilitation exercise.

Incentive problem and countermeasures of telemedicine providers in China / 中华医院管理杂志

Objective:To analyze the actual and expected incentives and key issues of telemedicine providers in China and to provide important references for optimizing telemedicine incentive policies.Methods:The sample data came from a questionnaire survey of 1 084 providers in 7 provinces of Fujian, Hainan, Henan, Hunan, Guizhou, Sichuan and Qinghai in October and November 2019 and a semi-structured interview data at 6 hospitals in Henan province in January 2020. Descriptive analysis was used to sort such data into text data for classified summation.Results:The greatest gaps were found between actual incentives and expected ones in expense subsidies, title promotion and excellence awards, with such gaps as high as 18.65, 28.26, 29.28 percentages among providers of junior, deputy senior and senior academic titles respectively. Hospitals fall short in providing adequate incentives for telemedicine providers, not to mention lack of differentiation and diversification in personnel incentives, and poor implementation of incentive policies.Conclusions:It is suggested to strengthen incentive demand analysis, break the homogenization bottleneck of incentive policies, and consolidate internal publicity and implementation of incentive policies.

A study on the telemedicine usage intention and key issues from the perspective of medical workers in China / 中华医院管理杂志

Objective:To analyze the usage intention and key issues of medical staff to use telemedicine, for improving telemedicine service system in China.Methods:From October to November 2019, medical workers of both the inviting party and invited party who experienced telemedicine in seven provinces of Fujian, Hainan, Henan, Hunan, Guizhou, Sichuan and Qinghai were selected for an online questionnaire survey. Areas covered included their usage intention, satisfaction and cognitive appraisal of telemedicine. Descriptive statistical analysis and non-parametric test were used to discuss the intention of further use, satisfaction and challenges of medical workers in various provinces and regions.Results:1 084 valid questionnaires were recovered. The data found the overall satisfaction was 98.62%, and the proportion of their intention of further use was 98.25%, and those from the eastern and western provinces presented higher intention of usage. The top challenges as reflected by these medical workers were named as follows: timeliness of consultation progress and information feedback; long latency time; low Internet speed, poor and interrupted Internet signal; inadequate system equipments and inconvenient operation; difficulties in remote physical checkup and overall understanding of patient conditions; as well as substandard, incomplete and poor medical records.Conclusions:These medical workers are satisfied with the telemedicine services and willing to continue to use telemedicine.For those existing problems, it is suggested to strengthen the infrastructure and optimize the process of telemedicine services, so as to encourage them in greater use of telemedicine.