Flexible Ureteroscopy with a Tip-Flexible Pressure-Controlling Ureteral Access Sheath for Renal Stones in Children.

INTRODUCTION: The aim of this study was to evaluate the safety and efficacy of flexible ureteroscopy using a tip-flexible pressure-controlling ureteral access sheath (TFPC-UAS) for renal stones in children. METHODS: Consecutive patients aged 5-18 years with renal stones of diameter 1-3 cm were enrolled between January 2022 and November 2023 at Ganzhou People's Hospital. The patients were treated with flexible ureteroscopy using the TFPC-UAS. The renal pelvic pressure (RPP) parameters were set as follows: control value at -10 mm Hg to 5 mm Hg, warning value at 20 mm Hg, and limit value at 30 mm Hg. The infusion flow rate was set to 100-120 mL/min. A holmium laser (276 µm) was used to fragment the stone at 2.0-2.5 J/pulse with a frequency of 20-30 pulses/s. The cases were analyzed for RPP, operative time, stone-free rate, and complications. RESULTS: A total of 21 consecutive patients were included. Two patients were switched to percutaneous nephrolithotomy owing to sheath placement failure. The RPP was -4.6 ± 2.1 mm Hg. The mean operative time was 56.5 ± 17.1 min. The postoperative hospitalization time was 1.5 ± 0.3 days. The stone-free rates at 1 day and 1 month after surgery were 81.0% and 85.7%, respectively. Residual stones in 2 patients were cleared after extracorporeal shockwave lithotripsy. Three cases of Clavien I complications and one case of Clavien II complications occurred. No major complications (Clavien grade III-V) were observed. CONCLUSIONS: Flexible ureteroscopy with a TFPC-UAS is safe and effective for renal stones in children.

Investigative biological therapies for primary Sjögren's syndrome.

Primary Sjögren's syndrome (pSS) is a chronic, systemic autoimmune disease characterized by dryness of the eyes and mouth. The histological feature is mononuclear cell infiltration in exocrine glands, primarily salivary and lachrymal glands. As the disease progresses, some other tissues and organs may be involved and extraglandular manifestations ensue. The major current treatments are palliative and empirical, and in most cases the outcomes are not satisfactory. Emerging data indicate a critical role of lymphocytes in its development and progression. While pioneering work targeting B cells has demonstrated some encouraging results, more trials are warranted to validate the safety and efficacy. In addition, modulation of T cell function with abatacept ameliorates the severity of pSS. Furthermore, clinical trials to inhibit important cytokines involved in its formation have been carried out. In this article, we summarize and compare current biological therapies in order to find new and effective treatments for pSS.

Human dopaminergic system in the exercise-cognition link.

While the dopaminergic system is important for cognitive processes, it is also sensitive to the influence of physical activity (PA). We summarize current evidence on whether PA-related changes in the human dopaminergic system are associated with alterations in cognitive performance, discuss recent advances, and highlight challenges and opportunities for future research.

Associations of meeting 24-hour movement behavior guidelines with prescribed eyeglasses/contact lenses among children and adolescents.

BACKGROUND: Vision health is crucial for many aspects of life especially in developing populations such as children and adolescents. However, there is a high proportion of children and adolescents who suffer from visual impairments. Notably, accumulating evidence indicates that meeting the 24-hour movement behaviors (24-HMB) guidelines is associated with positive physical and mental health outcomes in children and adolescents. However, the relationship between being prescribed eyeglasses/contact lenses and meeting the 24-HMB guidelines has yet to be investigated. Thus, this study aimed to address this gap in the existing literature by using the 2021 National Survey of Children's Health (NSCH) dataset. METHODS: In this cross-sectional study, data was retrieved from the 2021 NSCH. A total of 14,193 U.S. children and adolescents aged between 6 and 17 years were included for data analyses. We used items of the NSCH concerning the 24-HMB guidelines (i.e., physical activity, screen time, and sleep duration) and prescription of eyeglasses/contact lenses that were answered by the legal guardian of the children. Binary logistic regression was performed to investigate whether meeting the 24-HMB guidelines is associated with prescription eyeglasses/contact lenses and whether wearing eyeglasses/contact lenses predicts adherence to the 24-HMB guidelines among children and adolescents. RESULTS: More than half of the participants (59.53%) wore eyeglasses/contact lenses and only 8.40% of them met all three of the 24-HMB guidelines. Compared to meeting none of the 24-HMB guidelines, meeting one (OR = 0.76, 95% CI = 0.62-0.93, p = 0.008), two (OR = 0.54, 95% CI = 0.43-0.67, p < 0.001), and all three 24-HMB guidelines (OR = 0.47, 95% CI = 0.34-0.64, p < 0.001) were associated with a lower risk of being prescribed eyeglasses/contact lenses among children and adolescents. CONCLUSIONS: The findings of the current study provided evidence that the prevalence of U.S. children and adolescents aged between 6 and 17 years who wore eyeglasses/contact lenses was relatively high. Furthermore, meeting the 24-HMB guidelines was associated with a lower risk of being prescribed eyeglasses/contact lenses. Future studies focusing on the effects of 24-HMB interventions on vision health among children and adolescents are needed to better inform public health actions.

RNA N6-methyladenosine-modified-binding protein YTHDF1 promotes prostate cancer progression by regulating androgen function-related gene TRIM68.

PURPOSE: There is no report about the direct relationship between m6A modification and androgen receptor (AR)-related genes in prostate cancer (PC). We aimed to study the mechanisms of m6A methylation in regulating the pathogenesis of PC from the perspective of AR-related genes. METHODS: qRT-PCR was applied to detect the expression of m6A-related genes in PC cell with or without AR inhibitor. The effects of YTHDF1 knockdown on PC cell viability, apoptosis, migration and invasion were investigated using flow cytometry, wound healing and transwell assays, respectively. The mechanism of YTHDF1 action was investigated using m6A RNA immunoprecipitation (MeRIP) sequencing. The biological functions of YTHDF1 were also explored through in vivo experiments. RESULTS: YTHDF1 was significantly down-regulated in AR inhibitor group. YTHDF1 knockdown significantly decreased AR level, viability and m6A methylation level of PC cells. TRIM68 was identified as a direct target of YTHDF1. Both YTHDF1 and TRIM68 knockdown increased apoptosis, and decreased cell viability, migration, and invasion of PC cells, while TRIM68 overexpression reversed the effects of YTHDF1 knockdown on PC cells. In addition, knockdown of YTHDF1 or TRIM68 significantly decreased the m6A methylation level, and mRNA and protein levels of YTHDF1, TRIM68 and AR in PC cells, while TRIM68 overexpression increased the expression levels above. Furthermore, subcutaneous xenografts of nude mice also revealed that TRIM68 could reverse the effects of YTHDF1 knockdown in PC in vivo. CONCLUSION: This study suggested the key role of YTHDF1-mediated m6A modification in PC progression by regulating androgen function-related gene TRIM68 in PC.

Validity and reliability of the physical activity and social support scale among Chinese established adults.

Social support is a crucial factor that can facilitate regular engagement in physical activity. To assess the influence of social factors on the level of regular physical activity, the Physical Activity and Social Support Scale (PASSS) has been developed. However, the PASSS has yet to be validated in a Chinese sample of established adults. To address this gap in the literature, this study describes the development and psychometric evaluation of a Chinese version of the PASSS (PASSS-C) for established adults. PASSS-C was validated for a Chinese sample of adults aged between 30 and 45 years old (N = 1799). Structural validity was evaluated using confirmatory factor analysis (CFA) with Maximum Likelihood Method (MLM). Spearman's correlations between the PASSS-C and the International Physical Activity Questionnaire - Short Form (IPAQ-SF), the Social Support Rating Scale - Chinses Version (SSRS-C), and the Affective Exercise Experience Scale - Chinese Version (AFFEXX-C) were determined to examine the criterion validity. Cronbach's alpha coefficients and McDonald's omega coefficients were used to assess the internal consistency of the total scale and sub-scales of the PASSS-C. The results of the CFA suggest that the five-factor model had an acceptable fit (CFI = 0.99, GFI = 0.99, SRMR = 0.01, RMSEA = 0.02). Cronbach's alpha and McDonald's omega for the PASSS-C and its sub-scales ranged from 0.81 to 0.96. The results indicate that the PASSS-C has acceptable psychometric properties. Thus, the scale can be used to assess the levels of social support for physical activity in Chinese established adults.

Validation of sociocultural attitudes towards appearance questionnaire and its associations with body-related outcomes and eating disorders among Chinese adolescents.

Introduction: The Sociocultural Attitudes Towards Appearance Questionnaire-4 Revised (SATAQ-4R) has been widely used in Western countries to link body appearance that is related to eating disorders and body dissatisfaction being commonly reported by adolescents. However, a comprehensive psychometric validation of the SATAQ-4R in Chinese adolescent samples is still lacking. To this end, the aim of the current study was to validate the gender-appropriate SATAQ-4R in a sample of Chinese adolescents, following by an investigation of its associations with body-related outcomes and eating disorder symptoms. Methods: Two gender-specific studies were conducted to examine the psychometric properties of the SATAQ-4R-Female and SATAQ-4R-Male respectively among adolescent girls (Study1, N=344, with 73 participants at retest) and boys (Study2, N=335, with 64 participants at retest). Confirmatory factor analysis was employed to examine the factor structure and their test-retest reliability, the internal consistency and convergent validity were subsequently examined. Results: For the SATAQ-4R-Females, the seven-factor model has a reasonable fit, with Chi-square =1112.769 (p < 0.001), CFI = 0.91, RMSEA = 0.071, SRMR = 0.067. For the SATAR-4R-Males, an acceptable seven-factor model with Chi-square = 982.92 (p<0.001), CFI = 0.91, RMSEA = 0.08, SRMR= 0.06 was observed. With respect to test-retest reliability, the internal consistency for 7 subscales was rated as good (Cronbach's alpha =0.74 to 0.95) among female adolescents, likewise the internal consistency of the seven subscales was also rated as good (Cronbach's alpha =0.70 to 0.96) among male participants. Good convergent validity was observed, reflected by associations of the subscales of the gender-specific SATAQ-4R with muscularity-related attitude, body image-acceptance, body appearance, perceived stress level, symptoms of eating disorder and self-esteem. Discussion: For women and men, the original 7-factor structure was validated among Chinese adolescents, internal reliability coefficients for the seven subscale scores were good and test-retest reliability was acceptable. Our results also confirmed the convergent validity of the two different gender-appropriate scales.

Mindfulness group intervention improved self-compassion and resilience of children from single-parent families in Tibetan areas.

OBJECTIVE: The current study aimed to examine the effects of a mindfulness group intervention on self-compassion, psychological resilience, and mental health of children from single-parent families in Tibetan areas. METHODS: A total of 64 children from single-parent families in Tibetan areas were randomly allocated to a control group (n = 32) and an intervention group (n = 32). Participants in the control group received conventional education, while participants in the intervention group received 6-week mindfulness intervention in addition to the conventional education. Both groups completed the Five Facet Mindfulness Questionnaire (FFMQ), Self-compassion Scale (SCS), Resilience Scale for Chinese Adolescent (RSCA), and the Mental Health Test (MHT) before and after the intervention. RESULTS: After the intervention, the levels of mindfulness and self-compassion in the intervention group were significantly improved in relative to the control group. The positive cognition in the RSCA was significantly increased in the intervention group, whereas no significant change was observed in the control group. There was a trend towards lower self-blame in the MHT, but no significant impact of the intervention on the overall level of mental health was found. CONCLUSION: Results suggest that a 6-week mindfulness training effectively improve self-compassion and resilience of single-parent children. Thus, mindfulness training as a cost-effective approach can be arranged in the curriculum, which helps students develop high level of self-compassion and resilience. In addition, there may be a need to improve emotional control in order to improve mental health.

Associations between sedentary behavior and negative emotions in adolescents during home confinement: Mediating role of social support and sleep quality.

Background: Prolonged periods of sedentary behaviour, for instance, engendered by home confinement in Shenzhen city, has led to negative mental health consequences, especially in adolescents. Previous research suggests, in general, that sedentary behavior can increase negative emotions. However, the specific mechanism driving the relationship between sedentary behavior and negative emotions is still relatively unclear. Social support and sleep quality might partly explain the effect of sedentary behavior on negative emotions. Thus, the current study aimed to examine the associations between sedentary behavior and negative emotions, and to investigate if social support and sleep quality mediate such a relationship. Method: During home confinement due to the COVID-19 Omicron variant outbreak, 1179 middle and high school students in Shenzhen were invited to voluntarily complete an e-questionnaire, including the 21-item Depression Anxiety Stress Scale (DASS-21), the short form of the International Physical Activity Questionnaire (IPAQ-SF), the Social Support Rating Scale (SSRS) and the Pittsburgh Sleep Quality Index (PSQI). Data from 1065 participants were included in the analysis. Results: We observed significant sex-related and demografic-related differences in emotional (e.g., anxiety, stress and social support) and other outcome variables (e.g., sitting duration and PSQI score). Furthermore, sedentary behavior, social support, and sleep quality were associated with negative emotions (p < .01), even after controlling for sex, age, only-child case, body mass index, and metabolic equivalent level. In addition, social support and sleep quality partially mediated the association between sedentary behavior and negative emotions. Conclusion: The findings of the current study suggest that social support and sleep quality partially mediate the relationship between sedentary behavior and negative emotions in middle and high school students during home confinement in Shenzhen city.

Psychometric evaluation of the inventory of dimensions of emerging adulthood (IDEA) in China.

Background/Objective: Emerging adulthood (EA, age range between 18 to 29 years) is an important developmental stage that is characterized by marked social and psychological changes. Currently, its developmental features are quantified by the Inventory of the Dimensions of Emerging Adulthood (IDEA) but a validated Chinese version of this questionnaire (IDEA-C) is lacking. Thus, this research, which consists of two consecutive studies, aimed to investigate the psychometric properties of the translated IDEA in a Chinese sample of emerging adults. Method: Firstly, a forward-backward translation of the IDEA-C scale was conducted. Item analysis and exploratory factor analysis were performed in Sample 1a (n = 2438), followed by structural validity test in Sample 1b (n = 2461). Concurrent validity and internal consistency were evaluated in Sample 1(n = 4899). Finally, test-retest reliability was tested in Sample 2 (n = 185). Then, the second study aimed to test the factor structure proposed by study 1 in the non-student sample (n = 2200) by confirmatory factor analysis. In addition, the second study also investigated whether the attainment of college education influenced the EA experience of non-student emerging adults in China. And the association was examined between the socioeconomic status of emerging adults and the subscales of IDEA. Results: In the college sample, the IDEA-C scale presented a four-factor structure different from the original five-factor structure (χ2(190)=1116.84, p < 0.001; CFI = 0.97; TLI = 0.96; SRMR = 0.039; RMSEA = 0.050 [90%CI=0.047-0.052]). In addition, IDEA-C exhibited good internal consistency reliability (Cronbach's alpha >0.77), test-retest reliability (r>0.49, p < 0.01) and concurrent validity. And the CFA in non-student sample also showed an adequate fit indices (χ2(158) =710.10, p < 0.001, TLI=0.93, CFI=0.94, SRMR=0.038, RMSEA=0.04 [90%CI=0.037-0.040]) and an adequate internal consistency (Cronbach's alpha >0.64) and test-retest reliability (r>0.43, p < 0.01). Conclusion: The results of the present study confirmed that the Chinese version of the IDEA is found to be valid for measuring psychological characteristics of EA in Chinese-speaking samples of emerging adults.

Cangfudaotan decoction inhibits mitochondria-dependent apoptosis of granulosa cells in rats with polycystic ovarian syndrome.

Polycystic ovary syndrome (PCOS) is a universal endocrine and metabolic disorder prevalent in reproductive aged women. PCOS is often accompanied with insulin resistance (IR) which is an essential pathological factor. Although there is no known cure for PCOS, cangfudaotan (CFDT) decoction is widely used for the treatment of PCOS; nevertheless, the underlying mechanism is not clear. In this study, 40 Sprague-Dawley (SD) rats (female) were randomized to 4 groups, namely the control group, PCOS group, PCOS+CFDT group, and PCOS+metformin group. The rats in the control group were fed a normal-fat diet, intraperitoneally injected with 0.5% carboxymethyl cellulose (CMC, 1 mL/kg/d) for 21 days and orally given saline (1 mL/kg/d) for the next 4 weeks. The rats in the PCOS group, PCOS+CFDT group, and PCOS+Metformin group were fed a high-fat diet (HFD) and intraperitoneally injected with letrozole (1.0 mg/kg) for 21 days. During this period, we recorded the body weight, estrous cycles, and rate of pregnancy in all rats. We also observed the ovarian ultrastructure. Blood glucose indices, serum hormones, and inflammatory factors were also recorded. Then, we detected apoptotic and mitochondrial function, and observed mitochondria in ovarian granular cells by transmission electron microscopy. We also detected genes of ASK1/JNK pathway at mRNA and protein levels. The results showed that CFDT alleviated pathohistological damnification and apoptosis in PCOS rat model. In addition, CFDT improved ovarian function, reduced inflammatory response, inhibited apoptosis of granular cells, and inhibited the operation of ASK1/JNK pathway. These findings demonstrate the occurrence of ovary mitochondrial dysfunction and granular cell apoptosis in PCOS. CFDT can relieve mitochondria-dependent apoptosis by inhibiting the ASK1/JNK pathway in PCOS rats.

Renoprotective effect of Tanshinone IIA against kidney injury induced by ischemia-reperfusion in obese rats.

OBJECTIVE: Obesity enhances the frequency and severity of acute kidney injury (AKI) induced by renal ischemia-reperfusion (IR). Tanshinone IIA (TIIA) pre-treatment was used to alleviate renal injury induced by renal IR, and whether TIIA can attenuate renal cell apoptosis via modulating mitochondrial function through PI3K/Akt/Bad pathway in obese rats was examined. METHODS: Male rates were fed a high-fat diet for 8 weeks to generate obesity, followed by 30 min of kidney ischemia and 24 h reperfusion induced AKI. The male obese rates were given TIIA (5 mg/kg.d, 10 mg/kg.d, and 20 mg/kg.d) for 2 weeks before renal IR. RESULTS: TIIA alleviated the pathohistological injury and apoptosis induced by IR. In addition, TIIA improved renal function, inflammatory factor, and balance of oxidation and antioxidation in obese rats after renal IR. At the same time, TIIA can inhibit cell apoptosis by improving mitochondrial function through the PI3K/Akt/Bad pathway. Mitochondrial dysfunction was supported by decreasing intracellular ATP, respiration controlling rate (RCR), mitochondrial membrane potential (MMP), and mitochondrial respiratory chain complex enzymes, and by increasing ROS, the opening of mitochondrial permeability transition pore (mPTP), and the mtDNA damage. The injury to mitochondrial dynamic function was assessed by decreasing Drp1, and increasing Mfn1/2; and the injury of mitochondrial biogenesis was assessed by decreasing PGC-1, Nrf1, and TFam. CONCLUSIONS: Renal mitochondrial dysfunction occurs along with renal IR and can induce renal cell apoptosis. Obesity can aggravate apoptosis. TIIA can attenuate renal cell apoptosis via modulating mitochondrial function through PI3K/Akt/Bad pathway in obese rats.

The Flow-Clutch Scale: Translation and validation study of the Chinese version.

PURPOSE: The integrated model of flow and clutch provides a multistate perspective to the optimal experiences during physical exercises. Based on this model, the Flow-Clutch Scale (FCS) was developed. The current study is the first step to test the psychometric properties of a Chinese version of the FCS (FCS-C). METHOD: A confirmatory factor analysis (CFA) with Maximum Likelihood estimate was performed in Chinese athletes (N = 426) to explore the structural validity of the FCS-C . The Pearson correlations between the subscales of the FCS-C and "non-reactivity to inner experiences", "cognitive flexibility", and "self-consciousness" were explored to examine the concurrent validity. Cronbach's alpha coefficients were used to assess the internal consistency of the total scale and subscales. Moreover, the test-retest reliability was examined in a subsample (N = 53) using a two-week interval. RESULTS: The results of CFA suggested that the three-factor model showed an acceptable model fit (χ2 = 459.40, df = 120, CFI = 0.95, GFI = 0.90, SRMR = 0.03, RMSEA = 0.082 [90% CI = 0.074-0.09]). Concerning the correlations between the factor "characteristics of flow" and "self-consciousness", the concurrent validity was not satisfactory. Moreover, the test-retest coefficients ranged from 0.75 to 0.78 (p < .01) and Cronbach's alpha ranged from 0.87 to 0.96. CONCLUSION: Results indicated that the three-factor model of FCS-C is acceptable, whereas its validity is not satisfactory to appropriately examine flow and/or clutch states in Chinese athletes. In summary, the current translation and validation study of the FCS-C allows for future research on optimal exercise experiences in Chinese-speaking cohorts including a further cultural adaptation of the questionnaire.

Jian-Pi-Yi-Shen decoction inhibits mitochondria-dependent granulosa cell apoptosis in a rat model of POF.

As a widely applied traditional Chinese medicine (TCM), Jian-Pi-Yi-Shen (JPYS) decoction maybe applied in curing premature ovarian failure (POF) besides chronic kidney disease (CKD). In vivo experiments, 40 female SD (8-week-old) rats were randomized into four groups, namely, control group (negative control), POF model group, JPYS treatment group, and triptorelin treatment group (positive control). JPYS group was treated with JPYS decoction (oral, 11 g/kg) for 60 days, and the triptorelin group was treated with triptorelin (injection, 1.5 mg/kg) for 10 days before the administration of cyclophosphamide (CTX) (50 mg/kg body weight) to establish POF model. We examined apoptosis, mitochondrial function, and target gene (ASK1/JNK pathway and mitochondrial fusion/fission) expression. In vitro experiments, the KGN human granulosa cell line was used. Cells were pretreated with CTX (20, 40, and 60 µg/mL) for 24 h, followed by JPYS-containing serum (2, 4, and 8 %) for 24 h. Thereafter, these cells were employed to assess apoptosis, mitochondrial function, and target gene levels of protein and mRNA. In vivo, JPYS alleviated injury and suppressed apoptosis in POF rats. In addition, JPYS improved ovarian function. JPYS inhibit apoptosis of granulosa cells through improving mitochondrial function by activating ASK1/JNK pathway. In vitro, JPYS inhibited KGN cell apoptosis through inhibited ASK1/JNK pathway and improved mitochondrial function. The effects of GS-49977 were similar to those of JPYS. During POF, mitochondrial dysfunction occurs in the ovary and leads to granulosa cell apoptosis. JPYS decoction improves mitochondrial function and alleviates apoptosis through ASK1/JNK pathway.

Pediatric patients with familially inherited sitosterolemia: Two case reports.

Background: Sitosterolemia is a rare recessive genetic abnormality of hyperlipidemia; it is characterized by increased levels and accumulation of sitosterol in the plasma and local tissues. Case descriptions: The study subjects were two siblings (brother and sister) who had sitosterolemia with systemic multiple xanthomas as the main manifestation. The main clinical manifestations were hypercholesterolemia, premature atherosclerosis, arrhythmia, systemic multiple xanthomas, etc. After genetic testing, it was found that the patients had a compound heterozygous mutation of c.1324+1de1G in exon 7 and exon 9 of chromosome 2p21 of the adenosine triphosphate binding cassette transporter G family member 5(ABCG5) gene; the mutation at c.904+1G>A was of maternal origin, and the mutation at c. 1324+1de1G was of paternal origin. The compound heterozygous mutation of these two genes led to a metabolic disorder of plant sterols in vivo. Conclusion: Sitosterolemia is an autosomal recessive disease that could be effectively controlled after dietary control and oral lipid-lowering therapy with Ezetimibe. Xanthomas, which affects function and appearance, could be surgically removed, and primary wound healing could be achieved.

Clinical actionability of triaging DNA mismatch repair deficient colorectal cancer from biopsy samples using deep learning.

BACKGROUND: We aimed to develop a deep learning (DL) model to predict DNA mismatch repair (MMR) status in colorectal cancers (CRC) based on hematoxylin and eosin-stained whole-slide images (WSIs) and assess its clinical applicability. METHODS: The DL model was developed and validated through three-fold cross validation using 441 WSIs from the Cancer Genome Atlas (TCGA) and externally validated using 78 WSIs from the Pathology AI Platform (PAIP), and 355 WSIs from surgical specimens and 341 WSIs from biopsy specimens of the Sun Yet-sun University Cancer Center (SYSUCC). Domain adaption and multiple instance learning (MIL) techniques were adopted for model development. The performance of the models was evaluated using the area under the receiver operating characteristic curve (AUROC). A dual-threshold strategy was also built from the surgical cohorts and validated in the biopsy cohort. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), F1-score, and the percentage of patients avoiding IHC testing were evaluated. FINDINGS: The MIL model achieved an AUROC of 0·8888±0·0357 in the TCGA-validation cohort, 0·8806±0·0232 in the PAIP cohort, 0·8457±0·0233 in the SYSUCC-surgical cohort, and 0·7679±0·0342 in the SYSUCC-biopsy cohort. A dual-threshold triage strategy was used to rule-in and rule-out dMMR patients with remaining uncertain patients recommended for further IHC testing, which kept sensitivity higher than 90% and specificity higher than 95% on deficient MMR patient triage from both the surgical and biopsy specimens, result in more than half of patients avoiding IHC based MMR testing. INTERPRETATION: A DL-based method that could directly predict CRC MMR status from WSIs was successfully developed, and a dual-threshold triage strategy was established to minimize the number of patients for further IHC testing. FUNDING: The study was funded by the National Natural Science Foundation of China (82073159, 81871971 and 81700576), the Natural Science Foundation of Guangdong Province (No. 2021A1515011792 and No.2022A1515012403) and Medical Scientific Research Foundation of Guangdong Province of China (No. A2020392).

The roles of exercise tolerance and resilience in the effect of physical activity on emotional states among college students.

Background/objective: Negative emotional states, such as depression, anxiety, and stress challenge health care due to their long-term consequences for mental disorders. Accumulating evidence indicates that regular physical activity (PA) can positively influence negative emotional states. Among possible candidates, resilience and exercise tolerance in particular have the potential to partly explain the positive effects of PA on negative emotional states. Thus, the aim of this study was to investigate the association between PA and negative emotional states, and further determine the mediating effects of exercise tolerance and resilience in such a relationship. Method: In total, 1117 Chinese college students (50.4% female, Mage =18.90, SD=1.25) completed a psychosocial battery, including the 21-item Depression Anxiety Stress Scale (DASS-21), the Connor-Davidson Resilience Scale (CD-RISC), the Preference for and Tolerance of the Intensity of Exercise Questionnaire (PRETIE-Q), and the International Physical Activity Questionnaire short form (IPAQ-SF). Regression analysis was used to identify the serial multiple mediation, controlling for gender, age and BMI. Results: PA, exercise intensity-tolerance, and resilience were significantly negatively correlated with negative emotional states (Ps<.05). Further, exercise tolerance and resilience partially mediated the relationship between PA and negative emotional states. Conclusions: Resilience and exercise intensity-tolerance can be achieved through regularly engaging in PA, and these newly observed variables play critical roles in prevention of mental illnesses, especially college students who face various challenges. Recommended amount of PA should be incorporated into curriculum or sport clubs within a campus environment.

A possible new activator of PI3K-Huayu Qutan Recipe alleviates mitochondrial apoptosis in obesity rats with acute myocardial infarction.

Obesity, which has unknown pathogenesis, can increase the frequency and seriousness of acute myocardial infarction (AMI). This study evaluated effect of Huayu Qutan Recipe (HQR) pretreatment on myocardial apoptosis induced by AMI by regulating mitochondrial function via PI3K/Akt/Bad pathway in rats with obesity. For in vivo experiments, 60 male rats were randomly divided into 6 groups: sham group, AMI group, AMI (obese) group, 4.5, 9.0 and 18.0 g/kg/d HQR groups. The models fed on HQR with different concentrations for 2 weeks before AMI. For in vitro experiments, the cardiomyocytes line (H9c2) was used. Cells were pretreated with palmitic acid (PA) for 24 h, then to build hypoxia model followed by HQR-containing serum for 24 h. Related indicators were also detected. In vivo, HQR can lessen pathohistological damage and apoptosis after AMI. In addition, HQR improves blood fat levels, cardiac function, inflammatory factor, the balance of oxidation and antioxidation, as well as lessen infarction in rats with obesity after AMI. Meanwhile, HQR can diminish myocardial cell death by improving mitochondrial function via PI3K/Akt/Bad pathway activation. In vitro, HQR inhibited H9c2 cells apoptosis, improved mitochondrial function and activated the PI3K/Akt/Bad pathway, but effects can be peripeteiad by LY294002. Myocardial mitochondrial dysfunction occurs following AMI and can lead to myocardial apoptosis, which can be aggravated by obesity. HQR can relieve myocardial apoptosis by improving mitochondrial function via the PI3K/Akt/Bad pathway in rats with obesity.

Bone Marrow Mesenchymal Stem Cells Overexpressing HIF-1α Prevented the Progression of Glucocorticoid-Induced Avascular Osteonecrosis of Femoral Heads in Mice.

Glucocorticoid (GC)-induced avascular osteonecrosis of femoral head (AOFH) is a devastating complication, and no cures are currently available for it. Previous studies have demonstrated that implantation of bone marrow mesenchymal stem cells (BMMSCs) may prevent the progression of pre-collapse AOFH. Based on previous observations, we hypothesized that GCs induce AOFH via the COX-2 (cyclooxygenase-2)-PGE-2 (prostaglandin E2)-HIF-1α (hypoxia-inducible factor-1α) axis, and that modification of BMMSCs may improve the efficacy of their implantation. BMMSCs isolated from wild-type (WT) mice were treated with dexamethasone (Dex) and the results showed that Dex repressed the expression of COX-2. Femoral head samples harvested from both WT and COX-2 knock-out (COX-2-/-) mice were subjected to micro-computed tomography and histological examinations. Compared with their WT littermates, COX-2-/- mice had larger trabecular separations, diminished microvasculature, and reduced HIF-1α expression in their femoral heads. In vitro angiogenesis assays with tube formation and fetal metatarsal sprouting demonstrated that Dex repressed angiogenesis and PGE-2 antagonized its effects. An AOFH model was successfully established in C57BL/6J mice. In vitro experiment showed that BMMSCs infected with Lentivirus encoding HIF-1α (Lenti-HIF-1α) resulted in a robust increase in the production of HIF-1α protein. Implantation of BMMSCs overexpressing HIF-1α into femoral heads of AOFH mice significantly reduced osteonecrotic areas and enhanced bone repair, thus largely preserving the structural integrity of femoral heads. Our studies provide strong rationales for early intervention with core decompression and implantation of modified BMMSCs for GC-induced AOFH, which may spare patients from expensive and difficult surgical procedures.