Gender diversity has been linked to positive business results. Yet limited data exist to characterize the gender landscape in health technology, a field that draws employees from both biomedical engineering and medicine. To better understand the state of gender diversity in this industry, we developed a survey to explore leadership representation and perceptions of workplace equality, job satisfaction, and work-life balance. Data from 400 + health technology professionals revealed that women are significantly underrepresented in senior leadership and that men and women experience the workplace differently. Men believe in greater numbers than females that senior leaders are focused on recruiting and promoting women, promotion criteria are equitable, and the major barrier to leadership roles for women is work/family balance. In contrast, women perceive a less meritocratic and inclusive workplace in which their ability to rise is hampered by exclusion from influential communication networks and stereotyping/bias. Perhaps as a result, more than one-third of female respondents are considering leaving their current jobs, citing dissatisfaction with management and a desire for greater advancement opportunities. This study highlights significant gender perception differences in health technology that require further study and proactive remediation for the field to fully realize the benefits of gender diversity. Numerous studies have determined that gender diversity is a business imperative.28The US healthcare industry seemingly outperforms the rest of corporate America on gender diversity. Depending how healthcare is defined, women make up 50%3The high-technology industry, by comparison, continues to struggle with a significant gender gap—its workforce is only about one-quarter female.7Health technology, a growing field that includes medical device, device-based diagnostic, digital health, and health information technology companies, sits squarely between the healthcare and high-technology industries. However, its gender landscape remains obscure as it has not been extensively examined. In most research studies, health technology is grouped with larger healthcare sectors (payers and providers), other life sciences fields , or even included in high-technology rather than investigated separately.7Efforts have been made to evaluate gender diversity in the disciplines that feed health technology employment, most notably biomedical engineering and medicine. Prior studies have shown that the pipeline of women in these two specialties is robust. University-based biomedical engineering programs have better gender parity than almost any other engineering field. In 2017, women earned 44% of bachelor’s degrees, 43% of master’s degrees, and 39% of doctoral degrees in this discipline.1However, these “pipeline” figures do not tell the whole story. Even though the number of women entering biomedical engineering and, more broadly, science, technology, engineering, and math (STEM) fields is growing, men continue to outnumber women, especially in the leadership ranks.30Against this unclear and even contradictory backdrop, we initiated a survey to characterize the gender landscape specifically within health technology. Our goal was to better understand the industry’s current performance on factors such as female representation in leadership and perceptions of gender dynamics, workplace equality, job satisfaction, and work-life balance.The survey was designed to collect perceptual data of respondents’ experiences across companies in the health technology workplace to strengthen our understanding of gender dynamics in the field and improve the treatment of this subject in our educational programs. It included 104 questions in seven sections—demographics, industry experience, career path, mentoring, workplace perceptions, family life, and fundraising. Given our focus on gender-related issues, we did not collect data on ethnicity or race.We were particularly interested in understanding gender dynamics in small and mid-sized companies for three reasons. First, these organizations are generally considered the primary drivers of innovation in our field. Second, a significant portion of our trainees launch or take positions in small and mid-sized companies. And, third, these organizations often lack substantial resources to launch the types of diversity and inclusion initiatives that are emerging within larger corporations in health technology.To access individuals employed by small and mid-sized health technology companies, we asked the two largest trade organizations, the Medical Device Manufacturers Association (MDMA), which explicitly focuses on companies of this size, and AdvaMed Accel, the subgroup of the Advanced Medical Technology Association that serves medical technology companies with revenues under $100 million, to email the survey to their members. We also asked two other groups to send it: MedtechWomen, a California-based organization whose members we felt would be particularly interested in the survey topic, and the Stanford Biodesign Alumni Association, whose constituents have completed our fellowship. In total, these lists included 6548 individuals with some unknown  overlap among them.Using the Qualtrics platform , the survey was shared with individuals (as described) between December 17, 2018 and March 4, 2019. Each organization was asked to send an initial email and a second reminder. Respondents were offered a copy of the survey results (post publication) as an incentive for completion. No other inducements were provided.p < 0.05.Survey data from Qualtrics were exported into Microsoft Excel and reformatted for upload into Stata/IC 11.2 for Windows. All data were anonymized prior to being provided to the authors, and data analysis was performed under a waiver from Stanford’s Institutional Review Board. Comparisons between proportions were tested by Pearson’s Chi squared, with statistical significance at n = 152) and 62.3% female (n = 251). They varied in age from under 30 to over 60, with a majority  in the 40–59 age range. 80.1% were married (n = 323), 12.4% had never been married (n = 50), and 7.4% (n = 30) were separated or divorced. 73.2% (n = 295) had children.Survey responses were received from 403 unique individuals. Respondents were 37.7% male (n = 320) said that the desire to help people and improve healthcare was a major motivator. The next most frequently cited motivator was the desire for challenging work .When asked to rate factors that influenced their choice of a career in medtech, most respondents , 16.4% 11–25 employees (n = 66), 9.9% 26–50 employees (n = 40), 12.9% 52–100 employees (n = 52), 11.9% 101–500 (n = 48), and 25.6% more than 500 (n = 103).The companies where respondents were currently employed ranged from very small to very large as follows Fig. c: 23.3% p < 0.001). Men were disproportionately represented in the smallest companies, with 33.0% (n = 50) working at those with 10 employees or less. Women were more likely to work in large companies, with 32.0% (n = 80) holding positions at organizations with more than 500 employees.The proportion of male and female respondents varied by current company size (n = 77).5.2% of respondents were currently employed as independent contractors, 8.7% were individual contributors , 11.6% were managers, 16.4% were directors, 18.4% were VPs, 32.0% held C-suite titles , and 7.7% selected “other” , followed by 5.7% in Minnesota (n = 23) and 5.5% in Massachusetts (n = 22). All other states had less than 5% representation.56% of respondents reported that their company was headquartered in California (n = 40) worked in a company where the majority of leaders were women  worked in small companies (10 employees or less)  at their current companies, only 9.9% of respondents  and 69.7% of male respondents (n = 106) reported that they have or have had a mentor in their health technology career. When asked the gender of their most influential mentor, 86.8% of men (n = 92) and 55.6% of women (n = 85) cited a male mentor. 69% of all respondents with mentors (n = 179) indicated that those connections had been “very helpful” in their careers.61.0% of female respondents  and an inclusive environment  and asked to indicate whether they agree, disagree, or are neutral/have no opinion.p < 0.001).Across genders, respondent agreement with the proxy statements for job satisfaction and inclusive environment was linked to job retention. Of the 214 respondents who agreed with at least five of the seven proxy statements, only 15.4% were thinking about leaving their jobs. (Note: Five out of seven was subjectively chosen as a stronger indicator than agreement with a simple majority.) Of the 189 respondents who did not agree with five or more of the statements, 40.7% were thinking about making an employment change (n = 25) of men were considering a change compared to 33.9% (n = 85) of women (p < 0.001).Women responding to the survey were more likely than men to be thinking about leaving their current job. 16.4% (n = 38) reported that they were “dissatisfied with management” compared to 8.0% of men (n = 2). 42.4% of women (n = 36) were “seeking more opportunity for advancement” compared to 8.0% of men (n = 2). Approximately the same percentage of men  and women  were thinking of leaving because they were “seeking more interesting/challenging work.” 40.0% of men (n = 10) and 5.9% of women (n = 5) cited “other” reasons.When those considering a job change were asked why, 44.7% of women (n = 10) and 75.3% of women (n = 64) reported that they would seek another full-time job in health technology. 32.0% of men (n = 8) planned to start their own companies, while only 1.2% of females (n = 1) reported this intent. 12% of men (n = 3) and 12.9% of women (n = 11) planned to work part time or become a consultant.When those considering a job change were asked what they planned to do next, 40.0% of men, (p < 0.05).Being male and/or having a mentor were both associated with higher scores on the proxies for job satisfaction and inclusive environment Figs. a and 3b.p < 0.05). When we compared men with and without a mentor, men with mentors had significantly higher scores on their response to all job satisfactions proxies (p < 0.05). However, having a mentor did not result in any significant increase in men’s scores on proxies related to inclusive environment  said they viewed men and women as equal in strategic ability whereas only 77.0% of women (n = 191) shared the same opinion .When asked whether they personally viewed men and women as the same or different on a series of workplace characteristics, men were more likely than women to report that they viewed both genders the same, while women reported more variation between the genders. For example, 92.7% of men n = 10 said thRespondents who indicated that they believed men and women were “viewed differently” for any given characteristic were asked in a secondary question whether they thought that trait applied more to men or women. In general, male and female respondents presented with these follow-up questions agreed in their assessment of which traits applied more to men vs. women, especially on the characteristics of assertiveness, emotion, empathy, and executive presence.For example, for the characteristic of emotion, 150 men answered the preliminary question. 45 said the genders were “viewed differently” and were presented with the secondary question. 42 assigned emotion to women (93.3%) and 3 assigned that characteristic to men (6.7%). Similarly, 248 women answered the preliminary question and 144 said the genders were viewed differently with regard to emotion. Of those, 141 (97.9%) assigned emotion to women and 3 (2.1%) assigned that characteristic to men. Male and female responses were similar for empathy. The same pattern was present for assertiveness and executive presence, but with both male and female respondents overwhelmingly assigning those characteristics to men.p < 0.05).Next, respondents were presented with a series of issues and asked to use a four point system to rate where they believed the greatest inequalities exist between men and women in their workplace. Across all issues, men perceived lesser inequalities compared to women at significant levels  listed “exclusion from networks of communication and influence” as a top concern limiting women from advancing into senior leadership roles compared to 42.5% of men (n = 62), while 61.6% of men (n = 90) cited “desire to balance work and family” compared to 45.6% of women (n = 114).A set of barriers with the potential to hold women back from senior leadership roles was included in the survey and respondents were asked to select the top four they believed to be most problematic Fig. . 70.4% on = 215) responded affirmatively. 72.1% of women (n = 181) said that they had observed or experienced gender discrimination, while only 22.4% of men (n = 34) answered the same way (p < 0.001).Respondents were asked if they had observed or experienced gender discrimination while working in health technology. Overall, 53.3% (n = 96) focused around two main themes: (1) bias in hiring or promotion process, and (2) perceptions of qualifications and competence. The next most common theme  involved not being heard or taken seriously, not having one’s accomplishments acknowledged, or not feeling as though one’s opinion was valued.A write-in box provided for respondents to optionally describe the gender discrimination they had observed or experienced garnered 196 responses, with the plurality of comments  were in positions that required them to recruit and/or hire other employees. 69.1% of these individuals (n = 217) reported that they considered gender balance in their hiring decisions in addition to seeking the most qualified candidate, and 61.4%, (n = 134) stated that it was somewhat or very difficult to achieve.Of all respondents, 77.9% (n = 43) of responding males said this was due to a lack of qualified candidates compared to 59.5% of responding females . 40.4% of responding women (n = 34) chose the response “another reason.”When asked why it was difficult to achieve better gender balance in their company, 86.0% (n = 24) felt that “family responsibilities make it harder to get ahead at work” compared to 29.1% of women . 32.9% of men (n = 50) agreed with the statement “I can start a family and continue to advance at the same pace in my current company as my peers without children” compared to only 17.5% of women (p < 0.001).On the topic of work-life balance, there were significant differences between male and female responses. Only 15.8% of men (n = 19) and 19.0% of female respondents (n = 47) had taken time off of work—besides maternity/paternity leave—to focus on family. The majority of men reported that it took them less than 6 months to return to work when they were ready , while the majority of women indicated that it took them more than 6 months .Only 12.2% of male respondents  stated that they had been part of a management team seeking funding. When asked their title when fundraising, there were notable differences by gender. Within this subset of fundraisers, males represented 54.5% of founders/co-founders (n = 30), 65.7% of CEOs (n = 44), and 29.3% of senior staff (n = 27). Women made up 45.5% of founders/co-founders (n = 25) in this group, but disproportionately fewer CEOs  and disproportionately more senior staff .The last section of the survey focused on fundraising in health technology. A total of 247 respondents  and 8.6% of men (n = 10) who had been involved in fundraising had pitched to any entities focused on investing in women-led companies. 47.7% of men (n = 54) and 81.1% of women (n = 103) reported that less than 10% of the investors they met with were female.Only 18.0% of women (n = 11) said yes compared to 47.0% of women .When asked if they believed that male and female members of their pitch team were treated differently, only 9.7% of men  can be difficult. At a minimum, these groups provided a reliable channel to members of that target audience.Third, we are not able to confirm how many responses came to us through each channel or calculate an accurate response rate. Respondents were asked whether they were members of either trade group. 134 reported that they were members of MDMA, and 135 said they were members of AdvaMed. But we did not inquire about membership in MedTechWomen or the Stanford Biodesign Alumni Association. And, as noted, there was likely significant overlap among the mailing lists.Fourth, question construction could have prejudiced responses, although we attempted to minimize leading questions by trialing them before widespread dissemination. In addition, respondent self-selection may have biased results. In this study, in fact, substantially more women than men participated and it can be argued that those who responded represent a biased perspective. Additionally, the survey did not collect data on race or ethnicity. However, it is widely understood that those who are underrepresented by race and/or ethnicity can have even more challenging experiences in the workplace.18Finally, self-reported data are inherently subjective. However, the primary goal of this study was to characterize the subjective experience of health technology professionals on gender-related issues. Recording perceptual data is a well-established method of assessing unconscious gender bias at work.4Despite these limitations, the survey results shed light on two especially critical issues: the underrepresentation of women in senior leadership and striking differences in male and female perceptions of and experiences in the health technology workplace.The survey results suggest that there is a major gender imbalance in the senior leadership ranks of health technology companies. A majority of respondents work in organizations where women make up one-quarter or less of the senior leadership team. Only 10% are employed in companies with more than half female senior leaders Fig. a. FurtheRespondents pointed to multiple barriers that prevent women from reaching senior leadership Fig. . Respond13Female respondents also believe that disinclination to self-promote, a strategy generally considered necessary for professional advancement,Other areas flagged by both genders where major inequalities exist were the availability of role models, the pace of career advancement, and compensation Fig. . Without18do seem to agree is that gender stereotypes in the workplace are alive and well, with traits such as emotion, empathy, and collaboration assigned to women and assertiveness, executive presence, and ambition more often reserved for men.Overall, men responding to the survey believe that the work environment for their female colleagues is more meritocratic and inclusive than the women report. The data indicate that women experience a non-inclusive culture that, for the most part, their male colleagues may not even see. For example, far fewer female than male respondents believe that they fit in and are part of the team at work Fig. b. And whMale respondents also are more likely to believe that diversity and inclusion efforts are sufficient and/or the problem is not that great, whereas women are more likely to believe more improvements are needed Fig. b. For in18Our data come from a detailed survey with more than 400 responses from non-financially-incentivized participants who work specifically for health technology organizations. As such, they provide a credible first-look at the current state of gender diversity in the health technology field.The results are provocative and spotlight important issues, including the extent to which women are underrepresented in senior leadership and how vastly different men and women experience the workplace. They also provide more nuanced insights that should be used to fuel larger, more rigorous studies of gender equality in health technology. Minimally, the data should signal to health technology companies and training programs that our field is not immune to the gender-related issues that negatively affect the high technology industry, and that proactive steps to assess and improve their work environments on diversity and inclusivity may prevent them from losing talented female contributors.Major players in health technology have begun addressing issues of gender  diversity. As one example, Medtronic, the largest medical device company, has a Global Inclusion, Diversity, and Engagement team tasked with ensuring that, over time, the company’s workforce reflects the racial and gender makeup of the communities in which it is based.Importantly, academic programs focused on health technology innovation are in a unique position to help drive change from the bottom up. By increasing awareness and understanding of gender stereotypes and unconscious bias among our trainees, universities can equip future health technology leaders to build more inclusive workplaces as they go forward in their careers. Sharing data from this and other relevant studies is one way to engage students on the topic. Another is to leverage our project-based courses/programs to model desired behavior, help students create inclusive teams, and challenge them to practice behaviors that enable all team members to achieve their full potential. Additionally, academia can lead more studies to make sure our understanding of key issues is sound and that resulting improvement initiatives truly will make a difference.The benefits associated with increased diversity and inclusion are too great to be ignored. However, the results of our study indicate that current efforts around gender diversity and inclusion in health technology are not having a sufficient effect. Through greater awareness, evaluation, and action, health technology has the opportunity to lead other sectors in achieving these desired results.


Coordinating both hands during bimanual reaching is a complex task that can generate interference during action preparation as often indicated by prolonged reaction times for movements that require moving the two hands at different amplitudes. Individual processing constraints are thought to contribute to this interference effect. Most importantly, however, the amount of interference seems to depend considerably on overall task demands suggesting that interference increases as the available processing resources decrease. Here, we further investigated this idea by comparing performance in a simple direct cueing and a more difficult symbolic cueing task between three groups of participants that supposedly vary in their processing resources, i.e., musicians, young adults and older adults. We found that the size of interference effects during symbolic cueing varied in the tested groups: musicians showed the smallest and older adults the largest interference effects. More importantly, a regression model, using processing speed and processing capacity as predictor variables, revealed a clear link between the available processing resources and the size of the interference effect during symbolic cueing. In the easier direct cueing task, no reliable interference was observed on a group level. We propose that the susceptibility to bimanual interference is modulated by the task-specific processing requirements in relation with the available processing resources of an individual. Coordinating our two hands is an essential human skill that allows us to perform most everyday tasks, such as dressing ourselves, making breakfast, driving to work, or typing out a manuscript, with ease. Nevertheless, we have all experienced that there are certain limits to the independence with which we can move our two hands—for example, when trying to simultaneously rub our belly and tap our chest or when attempting to draw two different shapes with each hand  costs occur for spatially incongruent movements. Originally, it was suggested that the effect is primarily due to planning constraints on the motor level Heuer, . That isWhile there is still some debate about both explanations, most recent studies indicate that in fact, both processes contribute to the interference effect  not only show superior bimanual coordination performance  are expected to be relatively less prone to interference effects than individuals with less resources . In addition, individual differences should be more pronounced in more difficult tasks which pose higher demands  and are thus likely to be affected more strongly by reduced resources.We investigated three participant groups that are assumed to differ in their available resources. We recruited a group of 16 young adults with no instrumental expertise (non-musicians), a group of 16 young musicians, and a group of 16 older adults with no instrumental expertise and training. The young adult group consisted of undergraduate and postgraduate students of the University of Aberdeen  who did not actively play an instrument and have had no formal instrumental training or education. Two of the young adults were left-handed by self-report. The musicians group was also recruited from within the University of Aberdeen student population . All musicians had played their instrument for at least 7 years . Fourteen of the musicians played the piano, one saxophone and clarinet, and one played the drums. All but two of the participants still engaged in regular weekly practice. The 16 older adults were recruited using the University of Aberdeen, School of Psychology’s participant panel . Older adults did not report to have instrumental expertise or training. Any history of ophthalmologic and neurologic disorders as well as medications presumed to interfere with motor functioning were screened out by a detailed interview protocol. All participants had normal or corrected-to-normal vision. Furthermore, older adults had also been screened for mild cognitive impairment  maximally 6 months prior to participating in our study.All participants provided written informed consent prior to participating in the study and the protocol was approved by the ethics committee of the School of Psychology at the University of Aberdeen.The setup was identical to the one we have used and described previously . Small infrared markers were attached to the nails of the index finger of each hand using Blu Tack. The experiment was programmed in MATLAB using the Psychophysics Toolbox , leaving only the targets visible participants were supposed to point to. In the symbolic cueing condition, all four movement targets remained visible after the preview period, but centrally, two letters were displayed which cued the pointing targets. The left letter specified the movement amplitude for the left hand and the right letter the amplitude for the right hand . Each letter was 10 mm in size (line width 1.5 mm) and there was a 5 mm space between them. This symbolic cueing condition introduces an additional cognitive demand, namely, the translation of symbols into the spatial positions of the pointing targets. Note that in the direct cueing condition, we opted for identifying targets by a sudden offset of the two movement irrelevant locations rather than a sudden onset of the two relevant targets. This was done to ensure maximum similarity between the direct cueing and the symbolic cueing condition in which also all four possible movement targets were displayed before the movement was cued hence allowing partial pre-programming  was excluded from further data analysis as his reaction times frequently exceeded the response interval provided.α = 0.05 was used for all statistical analysis. The data set is available at zenodo.org, 10.5281/zenodo.1207940.To determine reaction time (RT), we computed the resultant velocity of the positional data obtained from both infrared markers. Movement onset and offset were defined by a velocity threshold . Figure We were initially interested in determining whether movement planning times vary systematically between the three participant groups and between cueing conditions that involve differential task demands. To this end, we conducted a 2 × 2 × 3 mixed ANOVA on RTs with the within-subject factors cueing condition (direct cueing vs. symbolic cueing) and movement congruency (symmetric vs. asymmetric movements) and the between subject factor F = 263.10, p < .001, F = 57.46, p < .001, F = 59.53, p < .001, p = .62), while the movement congruency effect in the symbolic cueing condition was highly significant . In other words, the size of the interference effect, calculated as the RT difference between asymmetric and symmetric movements, was about 2 ms in the direct cueing condition and 71 ms in the symbolic cueing condition  = 13.90, p < .001, F = 3.31, p = .046, F = 3.53, p = .038, p = .26).In addition, the initial ANOVA also confirmed a significant main effect of the between subject factor group, p < .001, and 46 ± 18 ms slower than non-musicians, p = .014). The difference between the two young groups approached significance . In the symbolic cueing condition, older adults reacted even more slowly than the two younger participant groups . In this condition, the RT difference between musicians and young adults increased to 63 ± 28 ms and was statistically significant, p = .03.Post-hoc analyses investigating the interaction effect between group and cueing condition revealed that RT differences between participant groups were slightly less pronounced in the direct cueing condition than in the symbolic cueing condition The size of the interference effects for the different groups and conditions is shown in Fig. Since the pre-analysis of our data suggested possible group differences in the synchronicity of the movement onsets for both hands see “”, we aimgroup) mixed ANOVA yielded significant results for all main and interaction effects . We followed up the three-way interaction, F = 7.86, p = .001, movement congruency) × 3 (group) mixed ANOVAs for each of the cueing conditions. In the direct cueing condition, RT offsets were affected neither by movement congruency nor by group . The average RT offset between the hands was about 15 ms. In contrast, we found significant main effects of movement congruency, F = 75.12, p < .001, F = 6.56, p = .003, F = 6.76, p = .003, A 2 (cueing condition) × 2 (movement congruency) × 3  RTs for symmetric movements in the direct cueing condition provide a baseline measure and can thus be considered as an indicator of general processing speed and (2) RT increase (costs) in the symbolic cueing condition as compared to the direct cueing condition when performing symmetric movements provides a measure for an individual’s vulnerability to additional task demands and can thus be considered an indicator of the available processing capacity. Please note that the labelling of both predictor variables as proxies for general processing speed and processing capacity is tentative as we did not determine both measures with independent tests. Keeping this in mind, the labels can, however, be considered appropriate descriptions of our parameters.r(47) = 0.15, p = .332 for general processing speed; r(47) = 0.27, p = .06 for processing capacity). However, we found strong correlations in the symbolic cueing condition in which pronounced interference was observed. Figure r(47) = 0.40, p = .006, and for available processing capacity a correlation of r(47) = 0.37, p = .011. Figure r(44) = 0.38, p = .009 for general processing speed, and r(44) = 0.35, p = .006 for processing capacity.In the direct cueing condition, the magnitude of the interference effects was marginal and variance between individuals was limited. Consequently, correlations between bimanual interference and both resource measures did not reach significance  = −0.01, p = .926. Using the enter method, we found that the two predictors explained 30% of the variance in the magnitude of the interference effect, F = 9.35, p < .001, R2 = 0.30. Evaluation of the β coefficients showed that both predictors had a significant partial effect in the full model, t(44) = 3.19, p = .003 for processing speed and t(44) = 2.96, p = .005, for processing capacity. Overall, the regression analysis validates that individual differences in susceptibility to the interference effect critically depends on processing resources.Multiple linear regression analysis was used to test whether the interference effect can be predicted by individuals’ processing resources, i.e., processing speed and processing capacity as indicated by RT costs. Both predictor variables were uncorrelated, It has been argued that one possible reason for why bimanual interference effects are not consistently observed might relate to differences in overall MTs. In particular, it has been speculated that if participants start moving their hand before movement amplitudes have been fully specified, and thus, motor programming occurs in flight, the motor interference due to amplitude specification may no longer be observable  = 30.3, p < .001, F = 132.8, p < .001, group, F = 7.03, p = .002, p ≤ .004. The difference in MTs between young and old adults was not significant (p = .67). The main effect of cueing condition indicated that MTs were overall quicker in the direct cueing condition (476 ± 10 ms) than in the symbolic cueing condition (509 ± 10 ms) and the main effect of congruency was caused by the fact that MTs tended to be about 34 ± 10 ms longer in the asymmetric conditions than in the symmetric ones. The main effects were further qualified by a significant two-way interaction between cueing condition and movement congruency, F = 65.36, p < .001, p > .15). Finally, the three-way interaction between all factors also reached significance, F = 3.42, p = .042, A 2 × 2 × 3 mixed ANOVA revealed main effects of cueing condition, r(47) = 0.17, p = .27, and even a positive correlation in the direct cueing condition, r(47) = 0.32, p = .027, indicating that participants with longer movement times actually tended to show larger congruency effects.Overall, there is no indication that more pronounced interference effects in older adults were driven by relatively shorter movement times. Further supporting this notion, we found no correlation between overall MTs and the size of the bimanual interference effect in the symbolic cueing condition, z-transformed the correlation coefficients and averaged them for the congruent (SS and LL) and incongruent (SL and LS) conditions. A 2 × 2 × 3 mixed ANOVA on the data revealed a main effect of cueing condition, F = 6.71, p = .013, F = 4.94, p = .031, ps ≥ .06). Post-hoc analyses showed that in the direct cueing condition, MT coupling was, as expected, stronger for congruent movements (z = 0.89) than for incongruent movements (z = 0.41). However, this was not the case in the symbolic cueing condition in which MTs were coupled equally strongly in both congruency conditions (congruent: z = 0.91 vs. incongruent: z = 1.12). Most importantly, however, movement time coupling was not moderated by group. Thus, it seems unlikely that our observed group differences in interference effects in RTs can be attributed to differences in the ability to execute decoupled hand movements.Finally, one might argue that potentially interference effects in RTs are confounded with an individual’s ability to decouple the movement execution times of both hands. In other words, the more individuals struggle to execute two movements with different spatial requirements the longer movement planning will take. To test for this possibility, we calculated for each participant the correlation between MTs of the left and right hand in all four movement conditions . We then Fisher F = 8.13, p = .007, p > .08). That is, all three participant groups showed similar movement accuracy as indicated by the distance errors. In addition, task demands as given by the different cueing conditions did not modulate movement accuracy.To test if differences in movement planning times between the three tested groups affected the resulting movement accuracy, we determined the final movement error as the Euclidean distance between the fingers’ end positions and the final target position. Figure In this study, we aimed to investigate how task demands in relation with the available processing resources modulate the bimanual interference effect, i.e., the finding that RTs tend to be prolonged for bimanual reaching movements with asymmetric amplitudes as compared to symmetric ones. The previous studies have shown that the size of the interference effect strongly depends on how these movements are cued. Specifically, interference effects were found to be larger and seem to be occurring more reliably when symbolic cueing conditions are employed. In contrast, during direct cueing, interference effects are strongly attenuated, or even disappear completely . Hence, participants who took longer to execute their movements, supposedly indicating a reduction in processing resources, were more likely to show an interference effect.Thus, our results provide evidence that differences in individual resources play a crucial role for the emergence of the interference effect. However, our data supported this link only for the symbolic cueing condition. In line with the previous literature, we found that interference effects were much more pronounced during symbolic cueing as compared to direct cueing. In fact, during direct cueing, none of the groups showed reliable interference effects, so that group differences eluded proper examination. Yet, it is worth noting that there was descriptively still an increase in the interference effect for older adults  as movements were similarly accurate for all our participant groups. The only effect we observed with regard to accuracy was the finding that movements were slightly less accurate for asymmetric as compared to symmetric movements which is congruent with the bimanual coordination literature  interpreted as indicating a decline in the motor processes with aging (e.g., Stelmach et al., In conclusion, our study provides first evidence that the interference effect during bimanual movement preparation is substantially modulated not only by task demands, but also by the processing resources available to an individual. In particular, we showed that both the general processing speed well as the available processing capacity are reliable predictors for the size of the bimanual interference effect during symbolic cueing. Our findings suggest that in order to understand the occurrence of the bimanual interference effect, it is not sufficient to focus merely on the differences between cueing conditions but also necessary to consider task demands in relation to participants’ available processing resources. The differential contributions of both factors and their precise interaction remain to be clarified.


Treatment of immune thrombocytopenia (ITP) usually involves long‐term use of immunosuppressive corticosteroids and splenectomy. However, these treatments often have side effects in patients. The Mongolian medicine Qishunbaolier (QSBLE) has a high curative effect, reduces the chances of relapse, and has no obvious side effects. This study was designed to identify potential therapeutic targets of QSBLE for treating ITP.To reveal differences in protein expression between ITP patients (ITPs) before and after QSBLE treatment, comparative proteomics studies were performed using isobaric tags for relative and absolute quantification (iTRAQ). The analysis used nanospray liquid chromatography/tandem mass spectrometry (nano‐LC/MS/MS) in positive ion electrospray ionization mode. Key proteins relevant to ITP were revealed by the Kyoto Encyclopedia of Genes and Genomes (KEGG) and other bioinformatics tools. Real‐time polymerase chain reaction (RT‐PCR) analysis was carried out for confirmation of differentially expressed proteins.A total of 982 differentially expressed proteins were identified in ITPs compared with the controls. Compared with the pre‐QSBLE treatment group, 61 differentially expressed proteins were identified in the post‐QSBLE treatment group, with 48 proteins being significantly upregulated and 13 downregulated. Twenty‐nine pathways were significantly enriched. Q6N030 and other proteins were the key players in the protein‐pathway network. Twenty proteins that may play important roles in the treatment of ITP were further filtered. RT‐PCR and Western blot analyses further confirmed that MIF, PGK1 and IGHM were upregulated in ITPs after QSBLE treatment, in accordance with the proteomics data.It is believed that the identified proteins and the results of bioinformatics analysis will provide a potential therapeutic target site for QSBLE for ITP therapy and biomarkers. Since the 1960s, Mongolian medicines have been used to treat a large number of diseases, including ITP, aplastic anemia (AA), allergic purpura (AP), and other bleeding disorders such as myelodysplastic syndrome (MDS).Our study aimed to use isobaric tags for relative and absolute quantification (iTRAQ) methods to determine the presence of differentially expressed proteins and biological pathways between ITPs before and after QSBLE treatment. Our results provide a comprehensive list of proteins associated with the progression of ITP; these may prove to be useful as potential markers or therapeutic targets.22.1This study was approved by the Institutional Review Board of the Affiliated Hospital of Inner Mongolia University for Nationalities, and is in line with the Helsinki Declaration. Written informed consent was obtained from each participant. Chronic ITPs were diagnosed after examination by the Inner Mongolia University for Nationalities Hospital. The diagnostic criteria for chronic ITP meet the guidelines for diagnosis and treatment.To rule out other complications, patients enrolled in the study needed to undergo standard health checks for health disorders, including hypertension, cancer, infection, diabetes, and other systemic diseases, before being diagnosed with ITP. During the treatment, ITPs were provided with 3–5 g QSBLE (weight‐based) per day. The efficacy of QSBLE was assessed by tracking platelet counts and bleeding scores, and tracking ITP treatment every 3 weeks for up to 12 weeks.2.2g for 20 min. The supernatant was quantified using a BCA Protein Assay Kit . The samples were stored at −80°C.In order to quantify protein sample preparation for mass spectrometry analysis, serum was depleted of most abundant proteins using a Human 14 multiple affinity removal system column  following the manufacturer's protocol. A 10 kDa ultrafiltration tube  was used for desalination and concentration of low‐abundance components. One volume of SDT (2% sodium dodecyl sulfate (SDS), 100 mM dithiothreitol (DTT), 100 mM Tris‐HCl, pH 7.6) buffer was added, and the solution was then boiled for 15 min and centrifuged at 14000 2.3Equal amounts of protein in the pre‐ and post‐QSBLE treatment ITP groups, and the control group, were denatured with 2% SDS, followed by reduction with 5 mM DTT, and alkylation with 20 mM iodoacetamide. In addition, modified sequencing grade trypsin  was digested overnight at 37°C in a 1:20 enzyme‐to‐substrate ratio. The peptide chain was labeled with iTRAQ reagent using a 4/8‐plex Multiplex reagent kit,  according to the manufacturer's instructions. Three biological replicates were prepared for all samples. For the biological replication, three 8‐plex iTRAQ sets were used. The samples were labeled as 113 , 114 (effective treatment in ITP patients before QSBLE treatment), 115 , 116 (effective treatment in ITP patients after QSBLE treatment), and 117 . All labeled samples were then combined and dried under vacuum.4, 5% acetonitrile (can), pH 10.0), and loaded onto a XBridge Peptide BEH C18 column . The peptides were eluted at a flow rate of 1 mL/min with a gradient of 0% buffer B  for 25 min, 0%–7% B during 25–30 min, 7%–40% B during 30–65 min, 40%–100% B during 65–70 min, and 100% B during 70–85 min. The elution was monitored at 214 nm, and fractions were collected every 1 min during 30–65 min. The collected fractions were dried down via vacuum centrifugation and dissolved with 0.1% formic acid (FA).A 100 μg peptide mixture of each sample was labeled using an iTRAQ reagent according to the manufacturer's instructions . The iTRAQ‐labeled peptides were fractionated2.4m/z 350–1800, the mass resolution was 70,000, the automatic gain control (AGC) target was set at 3e6, and the maximum ion injection time was 50 ms. The 10 most abundant ions in each full scan were then selected for higher‐energy collisional dissociation (HCD) to generate their respective product ion spectra, using a precursor ion isolation window of 2 m/z units. For these experiments the resolution was 17,500, the number of microscans was 1, the maximum injection time was 45 ms, and the normalized collision energy was 30 eV.Each sample was separated using a nanoliter flow rate Easy nLC system (Thermo Fisher Scientific). Buffer A was a 0.1% FA aqueous solution, and buffer B was a 0.1% FA/80% ACN aqueous solution. The column was equilibrated with 100% buffer A and the sample was loaded onto an analytical column  using an autosampler at a flow rate of 300 nL/min. A 1‐h gradient was programmed as follows: 0 min–5 min, linear gradient of buffer B from 0% to 6%; 5 min–45 min, linear gradient of B from 6% to 28%; 45 min–50 min, linear gradient of B from 28% to 38%; 50 min–55 min, linear gradient of buffer B from 38%–100%; 55 min − 60 min; and then maintained at 100% B. The separated compounds were analyzed by positive ion electrospray ionization mass spectrometry using a Q‐Exactive hybrid Quadrupole‐Orbitrap mass spectrometer (Thermo Fisher Scientific). The scan range was 2.5‐ΔΔCT. The primers used for the RT‐PCR are listed in Table RNA isoplus  was used to extract RNA from white blood cells before and after treatment in ITPs and normal controls. A PrimeScript™ RT reagent kit  was used for reverse transcription, following the manufacturer's instructions. RT‐PCR  was performed to quantify relative gene expression. GAPDH was used as an endogenous control. The relative concentration of candidate gene expression was calculated as described in the SYBR Green user manual (Thermo Fisher Scientific), using the formula 22.6Western blot analysis was performed as described previously.2.7www.cytoscape.org).The raw mass spectrometry data were acquired in a RAW file, and subjected to library identification and quantitative analysis using Mascot 2.5 and Proteome Discoverer software . Identification and analysis were performed using human Uniprot protein databases including known contaminants . Search parameters included trypsin as an enzyme, allowing up to 2 misses of cutting. The oxidation of methionine was set to dynamic modification, while the carbamoylation of cysteine, the N‐terminus of the peptide, and the iTRAQ modification of lysine were set to static modification. The precursor and fragment mass tolerances were set to 10 ppm and 0.05 Da, respectively. A 1% false discovery rate of peptide levels was used as a filter for peptide identification. The reporter ion quantification node was used for determining the relative expression pattern of the protein based on the relative intensity of the reporter ions of the corresponding peptide. Proteins that increase or decrease the ratio by 1.2‐fold or more between different groups are considered to be upregulated or downregulated, respectively. A protein‐pathway network analysis was carried out using Cytoscape, as described previously.2.8The ITP data pre‐ and post‐QSBLE treatments were compared using the Mann–Whitney T‐test in GraphPad  Prism 5.0 software. When the P‐value was <0.05, the difference was considered to be significant.33.19/L–300 × 109/L. The ITPs for this study were individuals who had chronic ITP due to bone penetration, and had a platelet count between 10 × 109/L and 100 × 109/L. There were no other secondary factors from thrombocytopenia, no obvious bleeding tendency, and patients had no liver or kidney dysfunction. Of the 18 ITPs, 10 were women and 8 were men. The ITPs were between 19 and 55 years old. Clinical information of all the patients is listed in Table 9/L after treatment. The results showed that patients taking QSBLE showed an increase in the platelet count from 46.9 × 109/L to 115.2 × 109/L, which effectively treated ITP  enrichment indicated that these differentially expressed proteins were mainly involved in biological processes such as biological regulation, biological adhesion, immune system process, signaling, locomotion, and developmental process Figure . In term3.4Staphylococcus aureus infection, tuberculosis, measles, transcriptional misregulation in cancer, asthma, autoimmune thyroid disease, systemic lupus erythematosus, rheumatoid arthritis, allograft rejection, primary immunodeficiency and viral myocarditis. , genome sequencing from molecular‐level information, especially large molecular data sets, and other high‐throughput experimental techniques. Pathway enrichment analysis was also performed by searching against the KEGG database. According to the results of the KEGG enrichment analyses, 29 pathways were included in the differentially expressed proteins Figure . The res. Figure . In orde. Figure . The res3.5It is unclear whether protein dysregulation is associated with the pathogenesis of ITP. We conclude that ITP‐associated proteins are abnormally expressed in ITPs, but can be restored to control levels after QSBLE treatment. To further screen for functional proteins, we reanalyzed differentially expressed proteins and focused on proteins that are abnormally expressed in ITP which are also expressed in control and treatment. Finally, we identified 20 proteins that met these criteria Figure  and 4D. 49/L, secondary to increased peripheral platelet destruction by autoantibodies. Some studies have reported increased risks of thromboembolic events in adults with ITP but thromboembolic events after intravenous immunoglobulin (IVIG) treatment in pediatric ITP are very rare, and only five cases have been reported to date.ITP is an autoimmune disorder defined by low platelet count under the level of 100 × 10There are many factors that can cause the pathogenesis of ITP, including abnormalities of various immune cells. Among them, the B‐cell‐activating factor (BAFF) in the tumor necrosis factor (TNF) family is an important part of normal B‐cell homeostasis.The goal of primary ITP therapy is to increase the patient's platelet count to a safe level and reduce the mortality rate, but excessive treatment should be avoided as much as possible. Emergency treatment of ITP is usually used for active bleeding in important areas or for patients requiring emergency surgery. In addition, thromboproliferative drugs have been added to the emergency treatment of ITP. As of now, first‐line treatment of ITP includes glucocorticoids and intravenous high‐dose gamma globulin.With the advances in proteomics technology, and separation, purification, and identification technologies, the use of proteomics to identify clinical markers has attracted a lot of attention. The technology of proteomics research is diverse, and it is helpful in all aspects of biomarker research.in vitro experiments, analyze the role of these proteins in the pathogenesis of ITP, and further test the safety, reliability, and effectiveness of the results through animal experiments in vivo.In this study, we identified a total of 982 differentially expressed proteins in ITP compared with controls, using iTRAQ labeling and nano‐LC/MS/MS analysis. Based on a change >1.2‐fold, 48 proteins were upregulated and 213 were downregulated after effective QSBLE treatment compared with pre‐QSBLE treatment , the [M + H]+ precursor ion, and the precursor ion charge.Click here for additional data file.


The aim of this prospective randomized controlled study was to evaluate whether pretreatment with a small dose of dezocine could prevent remifentanil-induced cough in general anesthesia induction.a prospective, randomized, controlled study.n = 105) and control group (n = 105). Patients were intravenously pre-administrated with dezocine 0.03 mg/kg (diluted to 5 mL) or the same volume of normal saline 1 min prior to remifentanil infusion. One minute later, intravenous injection of propofol 1.5 mg/kg and cisatracurium 0.1 mg/kg were given to all patients for induction of general anesthesia. The counts of coughs occurred during the anesthesia induction period were recorded and the severity of cough was scaled.A total of 210 patients receiving elective operative hysteroscopy from December 2018 to April 2019 were enrolled in the present study. They were randomly equally separated into dezocine group (P <  0.001). The two groups were not significantly different in heart rate and mean arterial pressure before the induction, before and after the intubation, and in operating time and postoperative visual analog scale pain scores.There were 7 cases of mild cough in dezocine group and 18 cases of mild cough, 12 cases of moderate cough and 4 cases of severe cough in control group. The incidence rate of cough was significantly lower and the severity of cough was obviously relieved in dezocine group compared to control group (6.67% vs. 32.38%, This study recommends the efficacy and safety of a pretreatment with a small dose of dezocine in reducing remifentanil-induced cough during general anesthesia.ChiCTR2000032035.Date of registration: Retrospectively registered on 2020/04/18. Opioids are conventionally used as adjunct drugs for induction of general anesthesia . ApplicaThere is a growing interest in suitable agents and methods to prevent remifentanil-induced cough. For instance, Kim et al. suggests that elongating injection time over than 60 s could inhibit remifentanil-cough during anesthesia in children . LimitedOur study pretreated the patients undergoing elective hysteroscopic surgery with a small dose of dezocine prior to remifentanil infusion with a view to investigating whether dezocine pretreatment is a reliable strategy to relieve the incidence and severity of remifentanil-induced cough. This prospective randomized controlled trial would provide some useful clues for further development of anesthesia management.2; a history of hypertension; severe arrhythmias; chronic bronchitis, asthma, or other respiratory diseases; increased intraocular pressure, intrathoracic pressure or intracranial pressure before surgery. Written informed consent was obtained from each participant.This study was approved by the National science and technology ethics committee  and registered in the Chinese Clinical Trial Register (registration number: ChiCTR2000032035). A total of 210 patients with ASA physical status I-II who received elective hysteroscopic surgery in our hospital from December 2018 to April 2019 were enrolled in this study. Exclusion criteria were: known hypersensitivity to the drugs used in this study; body mass index > 30 kg/mThe incidence of remifentanil (1.5 μg/kg)-induced cough in control group was around 30% in our early study (unpublished). We hypothesized that the incidence rate of cough in dezocine group was lower than 10%. Based on α = 0.05 (two-sided) and power = 0.95 (β = 0.05), a medium effect size (Cohen’s f = 0.25), the estimated sample size was 104. Taking the dropout into account, the sample size was set at 105 in each group.The 210 patients were randomly and equally divided into two groups: dezocine group and control group by a computer-generated allocation program.In brief, all patients of the two groups were fasted for 8 h. Peripheral venous access was established using a 20-gauge cannula on the dorsal hand in the operating room. Heart rate (HR) and blood pressure were monitored. Two minutes prior to induction of general anesthesia, patients of the dezocine group received intravenous infusion of dezocine 0.03 mg/kg (diluted to 5 mL), while patients of the control group received an injection of 5 mL normal saline.One minute later, remifentanil 1.5 μg/kg  was administrated to all patients of the two groups by a syringe pump at a rate of 600 mL/h, followed by intravenous injection of propofol 1.5 mg/kg and cisatracurium 0.1 mg/kg  1 min later to induce general anesthesia. Endotracheal intubation was then conducted and the patients were ventilated mechanically.2 < 90%) [HR and mean arterial pressure (MAP) before the anesthesia induction, immediately before and 1 min after intubation were recorded. Side effects such as vomiting , hypoxem2 < 90%)  or other2 < 90%) , 22. In P <  0.05 was defined as significance level.The primary endpoint was the incidence of cough in different groups. All statistical analyses were done by SPSS software 22.0 . Categorical data, such as ASA and incidence of cough were expressed as number (percentage) and compared between groups by Chi-square test or Wilcoxon rank-sum test. Continuous data, including age and body weight were expressed as mean ± standard deviation and compared by Students’ t test. Repeated continuous variables, including HR, MAP were analyzed by repeated measure ANOVA with Bonferroni correction. n = 105) or control group (n = 105). The age range of patients in dozocine group was 25–73 years and body weight range was 43–80 kg. The age range and body weight of patients in control group were 22–75 years and 42–89 kg, respectively. There was no significant difference between the two groups in age , body weight  and ASA class (P = 0.644)  of each patient was 100%. Adverse effects such as nausea and vomiting were not observed in any patient. HR and MAP were not significantly different between the two groups before the anesthesia induction, before intubation and 1 min after intubation . Additionally, there were no significant differences in operating time, 30-min and 60-min postoperative VAS pain scores (P > 0.05, Table As shown in Table Our study enrolled a total of 210 patients scheduled for hysteroscopic surgery who were equally randomized into dozocine group and control group. Patients in these two groups had similar age and body weight. The patients in the dozocine group received a small dose of dezocine prior to remifentanil administration, while patients in control group were given the same volume of normal saline. A pre-emptive administration of dezocine decreased the incidence of cough from 32.38 to 6.67% and relieved the severity of cough. These findings suggest that pretreatment with dezocine could effectively prohibit remifentanil-induced cough during general anesthesia induction in patients undergoing operative hysteroscopy.Hysteroscopy is an established endoscopic surgical procedure in obstetrics and gynecology practice for diagnosis and management of endometrial problems, with advantages of fewer complications, shorter recovery time and lower costs , 24. HowThe exact mechanisms behind opioid-induced cough remain elusive. One possible mechanism is that opioids cause suppression of central sympathetic outflow and strengthening of the vagus nerve, thus resulting in cough . PulmonaDezocine was thought to be a κ opioid receptor agonist, but recent data suggest it could be a κ opioid receptor antagonist . The couOur study showed that premedication of a low dose of dezocine was capable of effectively and safely repressing remifentanil-induced cough during general anesthesia in the patients receiving operative hysteroscopy. This study offers more insights concerning alternative regimens to prevent remifentanil-induced cough.


Tris(2‐ethylhexyl) phosphate  is a plasticizer and a flame retardant, while di(2‐ethylhexyl) phosphoric acid  is an oil additive and extraction solvent. Publicly‐available information on repeated exposure to these two related organophosphate compounds is fragmentary. Hence, adult male and female Fischer rats were exposed to TEHP  or DEHPA  by gavage for 28 consecutive days, to assess and compare their toxicities. Although significantly impaired BW gains and evidence of TEHP enzymatic hydrolysis to DEHPA were observed only in males, exposures to the highest TEHP and DEHPA doses often resulted in similar alterations of hematology, serum clinical chemistry and liver enzymatic activities in both males and females. The squamous epithelial hyperplasia and hyperkeratosis observed in the non‐glandular forestomach of rats exposed to the middle and high DEHPA doses were most likely caused by the slightly corrosive nature of this chemical. Although tubular degeneration and spermatid retention were observed only in the testes of males exposed to the highest TEHP dose, numerous periodic acid‐Schiff stained crystalline inclusions were observed in testis interstitial cells at all TEHP dose levels. No‐observed‐adverse‐effect levels for TEHP and DEHPA are proposed, but the lower serum pituitary hormone levels resulting from TEHP and DEHPA exposures and the perturbations of testicular histology observed in TEHP‐treated males deserve further investigation. Improved characterization of the toxicity of flame retardants will contribute to better informed substitution choices for legacy flame retardants phased‐out over health concerns. Tris(2‐ethylhexyl) phosphate (TEHP) is a plasticizer and a flame retardant, while the related di(2‐ethylhexyl) phosphoric acid (DEHPA) is an oil additive and extraction solvent. TEHP and DEHPA toxicities were compared in a rat 28‐day oral exposure study. Although TEHP hydrolysis to DEHPA was detected only in males, TEHP and DEHPA often had similar effects on the endpoints assessed in both males and females. The observed alterations of serum pituitary hormone levels and testis histological features in males warrant further investigation. The European Chemicals Agency reports annual tonnage bands of 1000‐10 000 tons for TEHP and 100‐1000 tons for DEHPA (http://www.echa.europa.eu).Tris(2‐ethylhexyl) phosphate (TEHP) is a plasticizer and flame retardant mostly used in polyvinyl chloride and other polymers, while di(2‐ethylhexyl) phosphoric acid (DEHPA) has found applications as an additive in industrial and automotive gear oils and in metal extraction processes    and DEHPA  were purchased from Sigma‐Aldrich. Corn oil  was obtained from a local grocery store. Unless otherwise stated, reagents were purchased from Sigma‐Aldrich.2.2R cages [Research Equipment Co.] with ad libitum access to food [Harlan Tecklad 2014] and water in a room maintained at 22 ± 1°C and 50% ± 10% humidity on a 12‐hour light cycle [06:00‐18:00 hours]) for 2 weeks. Male (218 ± 13 g) and female (153 ± 5 g) rats (approximately 11 weeks old) were then randomly divided into seven treatment groups of 14 animals , housed singly and weighed daily thereafter. Based on a pilot dose range finding study, rats were administered TEHP  or DEHPA  in a constant volume of corn oil (5 mL/kg BW) by gavage for 28 consecutive days. Rats from the control group received the same weight‐adjusted volume of corn oil. On the 21st day of dosing, rats spent the night (17:00‐06:00 hours) in a metabolic cage to collect urine and feces.Experimental procedures followed the Canadian Council on Animal Care guidelines and were approved by Health Canada's Institutional Animal Care Committee before the initiation of the study (HCO‐ACC protocol no. 2014‐020). The animal exposure phase was based on OECD Test Guideline 407 OECD, . Pair‐hom Tris/0.15% KCl buffer, pH 7.4 and centrifuged at 9000 g for 20 minutes to obtain the S9 fraction. Sera and liver S9 fractions were stored at −80°C until use.Rats were fasted on the night following the 28th daily dosing and euthanized under isoflurane anesthesia the next morning. Blood withdrawn from the abdominal aorta was used for hematology and serum clinical chemistry analyses. Heart, liver, spleen, kidneys, adrenals, thymus and thyroid were weighed. In males, testes, epididymis, prostate and seminal glands were weighed, while ovaries and uterus were weighed in females. A 2 g piece of liver was excised, homogenized in 3 mL of 0.05 2.3O‐deethylase (EROD) activity following the protocol of Lubet, Nims, Mayer, Cameron, and Schechtman  and pentoxyresorufin‐O‐dealkylase activities as described by Burke et al.  was used for the determination of the following hematological parameters: white blood cells (WBC), red blood cells, hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelet, mean platelet volume (MPV), neutrophils, lymphocytes, monocytes, eosinophils and basophils. An ABX Pentra 400 clinical analyzer (Horiba ABX Inc.) was used to measure total protein, albumin, creatinine, blood urea nitrogen (BUN), bilirubin, calcium, inorganic phosphate, cholesterol, triglycerides, alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma glutamyl transferase (GGT) in serum. To test for vitamin B6 deficiency, ALT and AST activities were reassessed in serum samples supplemented with 160 μmol pyridoxal 5′‐phosphate/L . After a 10‐minute pre‐incubation at room temperature with agitation, 30 μL of acetylthiocholine iodide substrate  was added. The plate was immediately read at 412 nm with readings every 2 minutes for 10 minutes . A standard curve of reduced glutathione was used to determine the change in absorbance per unit of ‐SH  except testes were fixed in 10% neutral buffered formalin solution for at least 24 hours before processing and embedding. The bone surrounding the pituitary gland  was decalcified for 24 hours at 4°C on a rotator using Richard‐Allan Scientific Decalcifying Solution (cat. no. 2205026) from Thermo Fisher Scientific. Formalin‐fixed tissues embedded in paraffin were cut in 5‐μm thick sections. Deparaffinized sections were stained using Modified Mayer's hematoxylin  and Instant Eosin . Testes were fixed in Modified Davidson Solution (cat. no. 64133‐50) from Electron Microscopy Sciences for 48 hours and then transferred to 10% neutral buffered formalin. Deparaffinized 5‐μm testis sections were stained using periodic acid  and Schiff's reagents , followed by counterstaining with Instant Hematoxylin . The tissues were assessed by pathologists using available guidelines from INHAND  using a subjective rating for each lesion based on a scaling system recommended by Mann et al. . High‐doTwo brain coronal sections  were assessed as described by Kaufmann et al. . One secOvaries (one section per ovary), transverse sections of the uterine horn at the middle region from both sides and longitudinal sections of the cervix and vagina were evaluated using guidelines drafted by Dixon et al. . Ovaries2.551 and DEHPA‐d34 standards were purchased from Toronto Research Chemicals. Acetonitrile, methanol and high‐performance liquid chromatography‐grade water were purchased from EMD Chemicals, Inc. Quality control normal human urine  was obtained from Lee Bio Solutions.Creatinine and total protein concentrations in overnight urine samples were measured using an ABX Pentra 400 clinical analyzer. The protocol for the quantification of TEHP and DEHPA was derived from a previously developed analytical method . Solid phase extraction (SPE) cartridges  from Waters were conditioned by sequential addition of 2 mL acetonitrile, methanol and water. Samples were loaded on the cartridge at a flow rate of approximately 5 mL/min. Two milliliters of 2% formic acid were added to the sample tubes to rinse and collect any residuals of target analytes. The rinse solution was loaded on to the SPE cartridge, which was allowed to dry under vacuum for 1 minute. Target analytes were eluted with 4 mL of 4% ammonium hydroxide in methanol. Extracts were concentrated to near dryness under a gentle stream of nitrogen and then reconstituted in 100 μL of 5% methanol in water before analysis by ultraperformance liquid chromatography (UPLC)‐tandem mass spectrometry (MS/MS).Briefly, urine samples were thawed and aliquots of 1 mL were diluted with 4% phosphoric acid (1:1). Samples were then mixed and spiked with 10 μL of 0.5 ng/μL Internal Standard mix (TEHP‐d18 column (1.7 μm × 2.1 mm × 50 mm) maintained at 40°C and attached to a Waters Van Guard BEH C18 pre‐column (1.7 μm × 2.1 mm × 5 mm). The mobile phase consisted of (A) 10 mm ammonium acetate in water and (B) methanol. The gradient programming was as follows: initial gradient 5% (B) to 90% (B) in 2.5 minutes, to 95% (B) in 1.75 minutes, hold for 4.2 minutes and equilibrate to 5% (B) for 4.08 minutes. The injection volume was 1.5 μL and the flow rate set at 0.22 mL/min. Quantifiers and qualifiers of multiple reaction monitoring transitions of the target analytes and internal standards used as well as associated collision energies are presented in Table Analysis of the extracts was carried out on a Waters Acquity UPLC system coupled to a Waters Xevo TQD MS/MS operated in electrospray‐positive (TEHP) or ‐negative (DEHPA) mode. Chromatographic separation of target analytes was performed using a Waters Acquity UPLC BEH Chttp://www.ecfr.gov). The relative percentage recoveries were based on the internal standards recoveries. To minimize the matrix effect, an extracted calibration curve was prepared in a surrogate blank matrix, which contained no detectable levels of any of the target analytes. The best‐suited matrix was rat urine obtained from the control group of another study. The matrix‐matched calibration curve was linear over a concentration range of 0.5‐500 ng/mL with a coefficient of correlation (r2) >0.998 for both TEHP  and DEHPA .The method detection limit (MDL) and the limit of quantitation (LOQ) were determined according to the EPA Regulation 40 CFR part 136 (appendix B) method (2.6P < .05. Urinary TEHP and DEHPA levels were compared using SAS Enterprise Guide 5.1 (SAS Institute). Q‐Q plots revealed that the dataset was not normally distributed. Data were log‐transformed and the normal distribution of the data was confirmed. A two‐factor (sex and treatment group) ANOVA using generalized linear models with the LSMEANS statement, which uses adjusted means (for other terms in the model) rather than simple arithmetic means, was then performed. The Bartlett's test for residuals revealed that the distribution of the error term was normal with a mean of zero, confirming the aptness of the model for the data. Differences from control group values and between males and females were assessed by the Tukey's studentized range (HSD) post‐hoc test and considered statistically significant for P < .05.The normality and homoscedasticity of initial and final BWs, BW gains, organ weights, liver enzymatic activities, hematology and clinical chemistry datasets were assessed using the Shapiro‐Wilk and Brown‐Forsythe tests, respectively. Datasets that did not meet these assumptions were log‐transformed and their normality and homoscedasticity reassessed using the same tests. Datasets that satisfied these assumptions were analyzed by one‐way ANOVA followed by Dunnett's post‐hoc test, while those that did not were analyzed by one‐way ANOVA on ranks  followed by Dunn's post‐hoc test. Rat growth curves were analyzed by two‐way (treatment group and exposure day) repeated measure ANOVA. These analyses were performed in SigmaPlot 12.5 (Systat Software) and differences were considered statistically significant for 33.1Rats exposed to TEHP or DEHPA by gavage for 28 consecutive days did not present any overt sign of distress or toxicity. Analysis of relative BW gains by two‐way repeated measure ANOVA identified statistically significant effects for treatment group and exposure day, and a significant interaction between treatment group and exposure day, in both males and females. However, while male daily weight gains in the high‐dose TEHP (3000 mg/kg BW/day) and DEHPA (180 mg/kg BW/day) treatment groups were significantly different from the control group, the daily weight gains of TEHP‐ and DEHPA‐treated females were not significantly different from control group females  were not noticed in any of the control or TEHP‐treated rats Table . These oTEHP is a weak PXR agonist in vitro , a seasonal breeder that presents large seasonal fluctuations in serum testosterone, luteinizing hormone and follicle‐stimulating hormone levels (Irby, Kerr, Risbridger, & de Kretser, Interestingly, testicular crystals can be observed in the Australian wild bush rat (5Although impaired weight gains and hydrolysis of TEHP to DEHPA were observed exclusively in male rats Figure  and 3, sThe authors have no conflict of interest to declare.


Considering that the efficacy results of the Japan lurasidone phase 3 trials for acute schizophrenia were inconsistent, we conducted a systematic review and a random‐effect model network meta‐analysis of those trials to examine whether lurasidone was beneficial for the treatment of Japanese patients with acute schizophrenia.The study included the double‐blind, randomized trial in Japan that included patients with acute schizophrenia. Efficacy outcomes were improvement of the Positive and Negative Syndrome Scale total score , positive (PANSS‐P), negative (PANSS‐N), and general (PANSS‐G) subscale scores; and Clinical Global Impression‐Severity Scale (CGI‐S) score and response rate. Other outcomes were discontinuation rates and incidence of individual adverse events.We included four studies . Although both lurasidone 40 mg/d (LUR40) and 80 mg/d (LUR80) outperformed placebo in PANSS‐T , PANSS‐P, and CGI‐S scores, LUR40 but not LUR80 outperformed placebo in PANSS‐N and PANSS‐G scores and response rate. LUR40 outperformed LUR80 regarding PANSS‐G score. Both LUR40 and LUR80 were associated with a higher incidence of akathisia, somnolence, and increased body weight compared with placebo. Compared with placebo, LUR40 was associated with a higher incidence of weight gain (≥7%), and LUR80 was associated with a higher incidence of dystonia and weight loss (≥7%) and higher Drug‐Induced Extrapyramidal Symptoms Scale score.Both LUR40 and LUR80 improved overall symptoms in Japanese patients with acute schizophrenia. However, LUR80 seemed to have a risk of extrapyramidal symptoms. Our network meta‐analysis included four studies .Both lurasidone 40 mg/d and 80 mg/d outperformed placebo in PANSS total score. Three double‐blind, randomized, placebo‐controlled, phase 3 trials (DBRPCP3T) of LUR for acute schizophrenia have been conducted.2This study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines Appendix .5 The 2.1We included only double‐blind randomized trials. We used Embase, PubMed, Scopus, and Cochrane Library; without language restrictions, from the date of inception of these databases to June 25, 2020. The following search strategy keywords were used: (lurasidone) AND (schizophrenia) AND (Asian OR Japan). Additional searches were conducted on ClinicalTrials.gov.2.2Intention‐to‐treat or modified intention‐to‐treat  data were used in the analysis.2.32 and I2 statistic using the netmeta.2 to empirical distributions of heterogeneity typically found in meta‐analyses.A Bayesian network meta‐analysis based on random‐effects models33.1The result of the literature search is shown in Figure 3.2Although both LUR40 and LUR80 outperformed placebo in PANSS‐T , PANSS‐P, and CGI‐S scores, LUR40 but not LUR80 outperformed placebo in PANSS‐N and PANSS‐G scores and response rate. LUR40 outperformed LUR80 regarding PANSS‐G score. Mean change PANSS‐T and 95%CI in LUR40, LUR80, and placebo were −14.51 , −8.57 , and −9.49 .3.3Both lurasidone 40 mg/d (LUR40) and 80 mg/d (LUR80) were associated with a higher incidence of akathisia, somnolence, and increased body weight gain compared with placebo. LUR40 was associated with a higher incidence of weight gain (≥7%) compared with placebo. LUR80 was associated with a higher incidence of dystonia and weight loss (≥7%) and having higher Drug‐Induced Extrapyramidal Symptoms Scale score compared with placebo. However, the risk of LUR40 and LUR80 for these outcomes was small. Only LUR40 was associated with a lower incidence of schizophrenia as an adverse event compared with placebo. There were not significant differences in other tolerability and safety outcomes among the groups. Mean all‐cause discontinuation and 95%CIs in LUR40, LUR80, and placebo were 27.6% , 34.6% , and 29.8% .3.4Although we did not detect global heterogeneity or global consistency for the primary outcome, we found local heterogeneity between LUR80 and placebo Appendix . We perf4Our meta‐analysis demonstrated that both LUR40 and LUR80 lead to a significant benefit for acute schizophrenia treatment in Japanese patients. The failure of these two DBRPCP3TsAlthough both LUR40 and LUR80 increased the mean body weight with very small effect on size, the incidence of weight loss seemed to be larger that of weight gain in all groups . Both LUR40 and LUR80 did not also influence the blood examination related to glucose and lipid metabolism. Thus, LUR seems to have very little effect on body weight and glucose and lipid metabolism, similar to the results of previous meta‐analysis.There were several limitations to this study. First, because the DBRPCP3Ts included Japanese and non‐Japanese patients, the results may not directly reflect the clinical practice in Japan. However, the number of Japanese patients in these trials was small. Second, although concomitant medication might influence the results in each trial, there were no significant differences in these outcomes among the groups.In conclusion, both LUR40 and LUR80 improved the overall symptoms of acute schizophrenia in Japanese patients. However, LUR80 seemed to be associated with a risk of extrapyramidal symptoms compare with LUR40.The present study was supported by the Grant‐in‐Aid for Scientific Research (C) (19K08082). Mr Nosaka is full‐time employee of Sumitomo Dainippon Pharma Co., Ltd. Other authors have declared that there are no conflicts of interest relating to the subject of this study.Dr Kishi received speaker's honoraria from Daiichi Sankyo, Dainippon Sumitomo, Eisai, Janssen, Otsuka, Meiji, Mochida, MSD, and Tanabe‐Mitsubishi (Yoshitomi); as well as research grants from the Japanese Ministry of Health, Labour and Welfare, Grant‐in‐Aid for Scientific Research (C), and Fujita Health University School of Medicine.Dr Sakuma has received speaker's honoraria from Eisai, Kissei, Meiji, Otsuka, and Torii; and has received a Fujita Health University School of Medicine research grant, as well as a Grant‐in‐Aid for Young Scientists (B).Dr Okuya has received speaker's honoraria from Meiji.Dr Iwata received speaker's honoraria from Astellas, Dainippon Sumitomo, Eli Lilly, GlaxoSmithKline, Janssen, Yoshitomi, Otsuka, Meiji, Shionogi, Novartis, and Pfizer; along with research grants from GlaxoSmithKline, Meiji, and Otsuka.Data Repository: The data that support the findings of this study are openly available in the articles of three studiesApproval of the research protocol by an Institutional Reviewer Board: Not applicable.Informed Consent: Not applicable.Registry and the Registration No. of the study/trial: Not applicable.Animal Studies: Not applicable.TK involved in the study conception and design and performed the statistical analysis. TK, TN, KS, and MO performed the acquisition and interpretation of the data. All the authors wrote the manuscript. NI supervised the review.5Supplementary MaterialClick here for additional data file.Appendix S1Click here for additional data file.


To investigate the effects of age, body mass index (BMI), bone mineral density (BMD), and levels of serum 25‐hydroxyvitamin D (25OHD) on hip fracture on the condition of the bone density of femoral neck having reached the threshold of osteoporosis.t‐test. Furthermore, the statistically significant factors were analyzed by multiple regression analysis to investigate the independent risk factors of hip fracture.A total of 252 postmenopausal women patients, whose bone density had reached the threshold of osteoporosis and age ≥50 years (50–98 years), collected from the Second Affiliated Hospital of Fujian Medical University from January 2015 to December 2018, were performed by retrospective analysis. According to whether or not they had a hip fracture, including femoral neck fracture or intertrochanteric fracture, the patients were divided into two groups, including 117 cases (50–84 years old) in the non‐hip fracture group and 135 cases (57–98 years old) in the hip fracture group. BMD was measured by Hologic Discovery A DXA bone mineral densitometer. Levels of serum 25OHD were detected by ROCHE detection instrument. Comparisons of age, BMI, bone density of femoral neck, and levels of serum 25OHD between the two groups were performed by using the Student's 2; bone density of femoral neck: (0.504 ± 0.067) g/cm2; T‐value of femoral neck: −3.1 ± 0.6; levels of serum 25OHD: (24.9 ± 8.5) ng/mL. The group with brittle hip fracture: 135 cases; average age: 80.7 ± 7.6 years; BMI: 20.3 ± 3.5 kg/m2; bone density of femoral neck: (0.426 ± 0.077) g/cm2; T‐value of femoral neck: −3.8 ± 0.7; levels of serum 25OHD: (15.9 ± 8.9) ng/mL. Age, BMI, bone density of femoral neck, and 25OHD level of the group without hip fracture were markedly lower than hip fracture group (P < 0.05). The results of logistic regression analysis suggested that age, bone density of femoral neck, and levels of serum 25OHD were independent risk factors for fragile hip fracture on the condition of the bone density of femoral neck having reached the threshold of osteoporosis.The group without hip fracture: 117 cases; average age: 67.4 ± 8.5 years; BMI: 22.3 ± 3.2 kg/mHigher age, lower levels of bone density and 25OHD are the main risk factors of hip fracture on the condition of the bone density of femoral neck having reached the threshold of osteoporosis. Brittle hip fracture is a serious complication of osteoporosis. Leung et al. used the data of the Amsterdam osteoarthritis cohort and found that serum 25OHD level was significantly associated with muscle strengthet al. reported that low serum 25OHD level was significantly associated with increased falls in elderly peopleet al.et al.et al. performed a prospective study of 5764 men and women, and showed that, compared with reference values (50–75 nmol/L), values <30 nmol/L were associated with significantly lower BMD of the femoral neckThe hip fracture risk was increased by 40% for each SD decrease in serum 25(OH)D level. Several possible mechanisms have been proposed for the associations between serum 25(OH)D level and the risk of fractures. Low serum 25(OH)D level usually indicates vitamin D deficiency. First, vitamin D increases the serum calcium concentrations and stimulates osteoblasts to produce RANKL, which is a protein that stimulates osteoclastogenesis. Low serum 25(OH)D level may increase parathyroid hormone (PTH) level, which may result in bone loss. Calcium mobilization from the bone is regulated by both vitamin D and PTH. Second, vitamin D deficiency has also been shown to be related to low muscle mass and muscle weakness. Koeckhoven Although many clinical factors are associated with brittle hip fracture, few studies have been conducted on fracture risk factors after BMD reaches the threshold of osteoporosis. It is of great clinical significance to identify these risk factors to prevent brittle hip fracture. Therefore, we aim to investigate several unanswered questions about the occurrence of brittle hip fracture after BMD reaches the threshold of osteoporosis. First, does BMD continue to affect the occurrence of brittle hip fracture? Second, are there any other factors besides BMD involved in brittle hip fracture? Third, what are the most significant risk factors among these independent factors analyzed by multivariate regression analysis? This study may provide guidance for effective clinical intervention.Considering that brittle hip fractures are more likely to occur in older age, BMD is an important factor in predicting fractures. Ninety per cent of hip fractures are caused by falls, and vitamin D status is associated with falls. Therefore, age, BMI, femoral neck BMD, and serum 25OHD were used as observation indexes in this study.Each patient provided informed consent for participation in the study. This retrospective study was conducted in accordance with the Declaration of Helsinki  and was approved by the Ethics Committee of Second Affiliated Hospital of Fujian Medical University.A total of 252 postmenopausal women patients with osteoporosis, collected from the inpatient department of Second Affiliated Hospital of Fujian Medical University from January 2015 to December 2018, were performed by retrospective analysis. According to whether or not they had a hip fracture, including femoral neck fracture or intertrochanteric fracture, they were divided into hip brittle fracture group and non‐hip fracture group. In the brittle hip fracture group, 135 cases were fresh fractures caused by falls; in the group without hip fractures, there were 117 cases.The inclusion criteria for all patients were the following: (i) BMD of femoral neck T ≤ −2.5 SD; (ii) age ≥50 years; (iii) menopause ≥1 year; and (iv) the hip fracture is a fresh fracture that occurred within the previous 2 weeks. Exclusion criteria: (i) patients who had been treated with anti‐osteoporosis drugs and vitamin D supplementation; (ii) secondary osteoporosis patients; and (iii) patients with abnormal function of liver and kidney and other important organs.Three indicators were measured for each patient enrolled in this study.BMI is the number obtained by dividing a person's weight in kilograms by their height in meters squared. It is an international standard that is commonly used to measure body fatness and health. BMI is a neutral and reliable indicator.Bone mineral density (BMD) was measured by Hologic Discovery A DXA bone mineral densitometer in the standard position with machine accuracy <1% and 0.25% coefficient of variation (% CV). Considering that the subjects were hip fractures, BMD of the hip and lumbar spine was measured and bone mineral density of the femoral neck was taken as an index. According to World Health Organization (WHO) diagnostic criteria, BMD of the femoral neck T ≤ −2.5 SD was defined as osteoporosis.in vivo. In the morning, 3 mL fasting venous blood was extracted, and ROCHE detection instrument (instrument model: Cobas e 601) was used. Vitamin D Total reagent was produced by ROCHE Company. The detection method was electrochemiluminescence. Criteria for judging vitamin D levels: lack, <20 ng/mL; insufficiency, ≥20 ng/mL and <30 ng/mL; adequacy, ≥30 ng/mL.Serum 25‐hydroxyvitamin D (25OHD) is currently recognized as the best indicator of vitamin D status t‐test. The risk factors of hip fracture were analyzed by unconditional logistic regression model. A value of P < 0.05 indicated a statistically significant difference.All statistical analyses were performed using SPSS 18.0 software . For quantitative variables, the data were expressed as mean ± SD, and compared by using the Student's 2; BMD of femoral neck: (0.504 ± 0.067) g/cm2; T‐value: −3.1 ± 0.57, 25OHD: (24.9 ± 8.5) ng/mL, 86 cases (73.5%) had 25OHD > 24 ng/mL. Hip fracture group: 135 cases were aged (80.7 ± 7.6) years, significantly higher than non‐hip fracture group; BMI: (20.3 ± 3.5) kg/m2, lower than that of non‐hip‐fracture group; BMD of femoral neck: (0.426 ± 0.077) g/cm2; T‐value: −3.8 ± 0.68, which was significantly lower than that of non‐hip‐fracture group; 25OHD: (15.9 ± 8.9) ng/mL, which was significantly lower than that of non‐hip‐fracture group, of which 114 cases (84.4%) had 25OHD ≤ 24 ng/mL  years; BMI: (22.3 ± 3.2) kg/mAge, serum 25OHD levels, and BMD are all independent influence factors for the occurrence of fragile hip fracture. Age, lower serum 25OHD levels and BMD will increase risk of hip fracture. In addition, BMI is not an independent influence factor for hip fracture (Table P = 0.000) on the condition of the femoral neck BMD reaching the threshold of osteoporosis. Furthermore, these factors were independent risk factors for hip fragile fracture.In this study, we found that hip fracture patients were older, had lower BMD and 25OHD (Fragile hip fractures are predominant in elderly women. It has been reported that 75% of hip fracture patients are over 65 years of age, and those aged between 70–89 years are the high‐risk age group for fragile hip fracturesThis study confirms that the hip fracture group is older and the femoral neck BMD is lower on the condition of BMD reaching the osteoporosis threshold. The femoral neck BMD comprehensively reflects the density of cancellous bone and cortical bone of the femoral neck, which constitutes about 80% of the bone strength. Therefore, the reduction of BMD will inevitably lead to the reduction of bone strength. This study confirms that age and further reduction of BMD are still risk factors for fragile hip fracture even when the femoral neck BMD reaches the threshold of osteoporosis.et al. reported that 25OHD was obviously associated with hip fractures in the elderly patientset al. found that 25OHD < 24 ng/mL markedly increased the risk of hip fracture in elderly patientset al. proposed that lateral tumbles increase the risk of hip fracture by five times, and that if the patient hits the greater trochanter in their fall, the risk of hip fracture will increase by 30 timesFalls and tumbles are the strongest risk factor for fractures in elderly patients, with 90% of hip fractures having a history of such activity. Low level of serum 25OHD is prone to fall and fracture. Annweiler and Beauchet found that the number of elderly patients who experienced falls and tumbles with a serum 25OHD below 20 ng/mL significantly increased the risk of fractureThis retrospective study has several limitations. First, the number of cases in this study is relatively small and cannot represent all people with BMD reaching osteoporosis. Secondly, the collection and recording of all patients' medical history is not carried out by the same person, and there may be omission or deviation in the medical history, resulting in a deviation of results.Age, BMD, and serum 25OHD level are independent factors that affect brittle hip fracture in postmenopausal women with osteoporosis. As age is an uncontrollable factor, to prevent osteoporotic hip fracture we should pay attention to the use of anti‐osteoporotic drugs such as bisphosphonate, which can effectively improve BMD and reduce fracture. Meanwhile, attention should also be paid to vitamin D supplementation, which can effectively improve serum 25OHD level, so as to reduce the incidence of hip in postmenopausal women with osteoporosis.