Early Mobilization after Cardiac Catheterization via Femoral Artery: A Systematic Review and Meta-Analysis.

Background: Early mobilization is one of the essential components of enhanced recovery after surgery (ERAS) pathways and has been shown to reduce complications and optimize patient outcomes. However, the effect of early mobilization for patients who undergo trans-femoral cardiac catheterization and the time for optimal mobilization timing remains controversial. We aimed to identify the safety of early mobilization and provide the optimum timing for early mobilization for patients undergoing trans-femoral cardiac catheterization. Methods: We searched MEDLINE, EMBASE, PubMed, Web of Science, Cochrane databases of systematic reviews, CINAHL, SCOPUS, China National Knowledge Infrastructure (CNKI), Wan Fang Database, and Chinese Science and Technology Periodical Database (VIP) comprehensively for randomized controlled trials associated with early mobilization, to explore its effects on patients after a trans-femoral cardiac catheterization. The risk of bias and heterogeneity of studies was assessed using the Revised Cochrane risk-of-bias tool for randomized trials (RoB 2) and I 2 index, respectively. The comprehensive Meta-analysis (CMA) was adopted to perform the meta-analysis. Results: We identified 14 trials with 2653 participants. Early mobilization was associated with significant decrease in back pain (mean difference (MD) = 0.634, 95% CI: 0.23-1.038; p = 0.002), especially in patients receiving instruction for early mobilization in 3 h~4 h versus 5 h~6 h (MD = 0.737, 95% CI: 0.431-1.043; p = 0.000) and 12 h versus 24 h (OR = 5.504, 95% CI: 1.646-18.407; p = 0.006) categories. The results of subgroup analysis also showed a significant risk reduction in urinary retention by early mobilization in 12 h versus 24 h (OR = 5.707, 95% CI: 1.859-17.521; p = 0.002) category. Conclusions: Early mobilization has not been shown to increase the risk of bleeding, hematoma, pseudoaneurysm, urinary retention, and pain at the puncture site after trans-femoral cardiac catheterization. Early mobilization is a practical initiative in ERAS, and it may be safe and feasible to advance the mobilization to 2 h~4 h.

Aspirin boosts the synergistic effect of EGFR/p53 inhibitors on lung cancer cells by regulating AKT/mTOR and p53 pathways.

The regimen of afatinib and vinorelbine has been used to treat breast or lung cancer cells with some limitations. Aspirin alone or in combination with other agents has shown unique efficacy in the treatment of cancer. We designed a preclinical study to investigate whether the triple therapy of aspirin, afatinib, and vinorelbine could synergistically inhibit the growth of p53 wild-type nonsmall cell lung cancer (NSCLC) cells. Three NSCLC cells A549, H460, and H1975 were selected to study the effect of triple therapy on cell proliferation and apoptosis. Compared to single agents, triple therapy synergistically inhibited the proliferation of lung cancer cells with combination index <1. Meanwhile, the therapeutic index of triple therapy was superior to that of single agents, indicating a balance between efficacy and safety in the combination of three agents. Mechanistic studies showed that triple therapy significantly induced apoptosis by decreasing mitochondrial membrane potential, increasing reactive oxygen species, and regulating mitochondria-related proteins. Moreover, epidermal growth factor receptor (EGFR) downstream signaling proteins including JNK, AKT, and mTOR were dramatically suppressed and p53 was substantially increased after NSCLC cells were exposed to the triple therapy. We provided evidence that the triple therapy of aspirin, afatinib and vinorelbine synergistically inhibited lung cancer cell growth through inactivation of the EGFR/AKT/mTOR pathway and accumulation of p53, providing a new treatment strategy for patients with p53 wild-type NSCLC.

A nomogram for evaluation and analysis of difficulty in retroperitoneal laparoscopic adrenalectomy: A single-center study with prospective validation using LASSO-logistic regression.

Background: While it is known that inaccurate evaluation for retroperitoneal laparoscopic adrenalectomy (RPLA) can affect the surgical results of patients, no stable and effective prediction model for the procedure exists. In this study, we aimed to develop a computed tomography (CT) -based radiological-clinical prediction model for evaluating the surgical difficulty of RPLA. Method: Data from 398 patients with adrenal tumors treated by RPLA in a single center from August 2014 to December 2020 were retrospectively analyzed and divided into sets. The influencing factors were selected by least absolute shrinkage and selection operator regression model (LASSO). Additionally, the nomogram was constructed. A receiver operating characteristic curve was used to analyze the prediction efficiency of the nomogram. The C-index and bootstrap self-sampling methods were used to verify the discrimination and consistency of the nomogram. Result: The following 11 independent influencing factors were selected by LASSO: body mass index, diabetes mellitus, scoliosis, hyperlipidemia, history of operation, tumor diameter, distance from adrenal tumor to upper pole of kidney, retro renal fat area, hyperaldosteronism, pheochromocytoma and paraganglioma, and myelolipoma. The area under the curve (AUC) of the training set was 0.787, and 0.844 in the internal validation set. Decision curve analyses indicated the model to be useful. An additional 117 patients were recruited for prospective validation, and AUC was 0.848. Conclusion: This study developed a radiological-clinical prediction model proposed for predicting the difficulty of RPLA procedures. This model was suitable, accessible, and helpful for individualized surgical preparation and reduced operational risk. Thus, this model could contribute to more patients' benefit in circumventing surgical difficulties because of accurate predictive abilities.

The relationship between bladder storage function and frequent micturition after TURP.

PURPOSE: To investigate the relationship between preoperative bladder function and frequent micturition after transurethral resection of prostate in patients with benign prostatic hyperplasia. METHODS: We retrospectively included 80 eligible patients aged 54-87 years (mean age 69.8 years) who underwent transurethral resection of the prostate at our hospital from January 2019 to October 2021. Patients were divided into detrusor overactivity positive and negative groups, and according to bladder compliance, they were divided into: low (G1), normal (G2), and high (G3) bladder compliance groups. RESULTS: The incidence and score of postoperative frequent micturition in the detrusor overactivity positive group were higher than those in the detrusor overactivity negative group. The incidence and score of postoperative frequent micturition in the low bladder compliance group were higher than those in the normal and high bladder compliance groups. There was no significant difference in the score of frequent micturition between the normal and high bladder compliance groups. Multivariate logistic regression analysis indicated that frequent micturition was significantly correlated with detrusor overactivity, bladder compliance, maximum cystometric capacity, and maximum flow rate. CONCLUSION: This study confirmed that patients with abnormal bladder storage functions (detrusor instability and low bladder compliance) before transurethral resection of the prostate were likely to have frequent and severe urination after transurethral resection of the prostate. Therefore, preoperative urodynamic examination to evaluate the urinary storage function of patients with benign prostatic hyperplasia is of great significance to predict the occurrence and degree of postoperative frequent micturition.

The impact of watching real-time videos of flexible ureteroscopic lithotripsy on anxiety and depression in patients.

PURPOSE: This study examines the effect of intraoperative doctor-patient communication with real-time videos in flexible ureteroscopic lithotripsy on patients' anxiety and depression. METHODS: Patients with upper urinary tract calculi were randomised into four groups. Group A (n = 29) watched the real-time operation video, but did not accept the relevant explanation during the operation; Group B (n = 31) received an explanation about the operation process during the operation alone. Patients in Group C (n = 33) watched the real-time operation video and received an explanation about the operation process during the operation. Group D (n = 31) neither watched the operation video nor received an explanation about the operation process. The self-rated anxiety and depression scores of the patients were evaluated using the self-rating anxiety scale (SAS) and the self-rating depression scale (SDS) before and after the operation. RESULTS: The clinical and demographic profiles (average age, gender distribution, educational level, body mass index, stone size, the position of stones in each groups, the length of stayand the numbers of severe postoperative complications) of the for groups showed no preoperation difference (P > 0.05). The preoperative anxiety scores and the preoperative depression scores showed no significant difference in the four groups (P > 0.05). The scores of postoperative anxiety and depression in groups A (n = 29), B (n = 31), and C (n = 33) were significantly lower than those in Group D (n = 31), (P < 0. 05). Compared to groups A and B, the scores of anxiety and depression in Group C were significantly decreased (P < 0.05). CONCLUSION: During flexible ureteroscopic lithotripsy, doctor-patient communication combined with real-time video can significantly reduce patients' postoperative anxiety and depression, and contribute to their physical and mental health recovery.

Perioperative factors influencing the difficulty of retroperitoneal laparoscopic adrenalectomy: a single-center retrospective study.

PURPOSE: Identifying patients in whom adrenalectomy may be more difficult can help with surgical decision-making. This study investigated the perioperative factors affecting the difficulty of retroperitoneal laparoscopic adrenalectomy (RLA). METHODS: Sixty-eight patients who underwent RLA at our hospital between December 1, 2020 and May 1, 2021 were included. The difficulty of RLA was assessed by operating time and intraoperative blood loss. We analyzed the relationship between surgical difficulty and patient sex, age, and body mass index, pathological type, tumor side, tumor size, distance from the lower pole of the adrenal tumor to the upper pole of the kidney (DAK), and distance from the lower pole of the adrenal tumor to the renal pedicle (DARP). RESULTS: Mean operating time was 105.38 ± 33.31 min and mean intraoperative blood loss was 32.28 ± 22.88 ml. Univariate linear regression analysis showed that age (P = 0.047), tumor size (P = 0.002), DAK (P = 0.002), and DARP (P < 0.001) were significantly correlated with a longer operating time. Univariate logistic regression analysis showed that DARP (P = 0.001), DAK (P = 0.001), tumor size (P = 0.002), and age (P = 0.033) were significantly correlated with a longer operating time. Multivariate logistic regression indicated that DARP (OR 5.341; 95% CI 1.704-16.739; P = 0.004), and tumor size (OR 4.433; 95% CI 1.434-13.709; P = 0.010) were independent predictors of operating time. CONCLUSION: Age, tumor size, DAK, and DARP were predictors of the difficulty of RLA. Older age, lower DARP and DAK, and a larger tumor size were associated with a longer operating time. DARP and tumor size were independent predictors of surgical difficulty.

Qualitative and Quantitative Analysis on Flavonoid Distribution in Different Floral Parts of 42 Hemerocallis Accessions.

The Hemerocallis accessions is widely consumed as nutritious vegetable and traditional medicine in eastern Asia and used as an ornamental flower worldwide. Compared with most other horticultural products, its flower is richer in polyphenols, flavonoids, carotenoids, and anthocyanins. Therefore, the flower has strong antioxidant activity that inhibits cancer cell proliferation, which could used for health and pharmaceutical purposes. The flavonoids composition and distribution in the flowers, and the content varied between different accssions is still unclear. In this context, eight flavonols, two flavones, and two anthocyanins were determined in Hemerocallis flower by high-performance liquid chromatography (HPLC) coupled with photodiode array and mass spectrometric detectors. Rutin was the most abundant flavonols and cyanidin 3,5-glucoside and cyanidin 3-rutinoside were the major anthocyanins in Hemerocallis tepals, resulting in flower petal coloration, and their content in the petal was higher than that of the sepal. Hierarchical cluster analysis grouped the 42 accessions into four groups, and they were significantly different (p < 0.05) from each other in the ten significant compounds by One-way ANOVA. Overall, the qualitative and quantitative analysis of flavonoid constituents in six floral parts of 42 Hemerocallis accessions were elucidated, which could be helpful for the food and pharmaceutical industries, and lay the foundation for the Hemerocallis flower color research.

The Effects of Age, Period, and Cohort on the Mortality of Cervical Cancer in Three High-Income Countries: Canada, Korea, and Italy.

BACKGROUND: As the second most common gynecologic cancer worldwide, cervical cancer has led to morbidity and mortality in thousands of women. Our study is aimed at comparing the long-term trends of mortality rates for cervical cancer in three high-income countries-Canada, Korea, and Italy-and analyzing the detached effects of chronological age, time period, and birth cohort by age-period-cohort (APC) analysis. METHODS: Joinpoint regression was used in this study, and the age-period-cohort model combined with the intrinsic estimator method was also applied to estimate the detached effect of each age, time period, and birth cohort on cervical cancer mortality. RESULTS: For the overall trends of ASMRs for cervical cancer, the rates for Canada and Italy generally decreased during the whole observation periods while the rate for Korea exhibited a significant increase from 1986 to 2003. The APC analysis suggested that the cancer mortality risks consistently increased with age in the age groups including women aged 20 to 50 years in all areas. The period effect exhibited a general upward trend for both Korea and Italy, while a decreased trend was observed for Canada during the whole observation period. The mortality risk generally decreased with birth cohort, except there was a slight increase for younger generations in the three countries. CONCLUSIONS: Our study shows that the overall decrease in the cohort effect may have contributed to the reduced mortality rate for Italy and Canada, and the increased period effects and cohort effect in younger generations may have led to the increase in cancer mortality rate for Korea.

Suppressed expression of Cbl-b by NF-κB mediates icotinib resistance in EGFR-mutant non-small-cell lung cancer.

Although epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) could greatly improve the prognosis of NSCLC patients harboring activating EGFR mutations, drug resistance still remains a major obstacle to successful treatment. Our previous study found that the EGFR-TKI icotinib could upregulate the expression of Casitas-B-lineage lymphoma protein-B (Cbl-b), an E3 ubiquitin ligase. In the present study, we aimed to clarify the potential role of Cbl-b in the resistance to icotinib, and the underlying mechanisms using EGFR-mutant cell lines. We found that icotinib inhibited the proliferation of mutant-EGFR NSCLC cells (PC9 and HCC827), and upregulated the expression of Cbl-b at both the protein and mRNA levels. Cbl-b knockdown decreased the sensitivity of PC9 and HCC827 cells to icotinib, and partially restored icotinib-inhibited AKT activation in PC9 cells. On the contrary, Cbl-b overexpression could partly reverse the drug resistance in PC9 icotinib-resistant cells (PC9/IcoR). Moreover, overexpressing p65, the main member of transcription factor NF-κB family, reversed the icotinib-mediated upregulation of Cbl-b. Collectively, these data suggest that icotinib could upregulate Cbl-b mediated by NF-κB inhibition, and Cbl-b contribute to the icotinib sensitivity in EGFR-mutant NSCLC cells. This study highlights that low expression of Cbl-b might be the key obstacles in the efficacy of icotinib therapy.

Tyrosine kinase inhibitor-induced IL-6/STAT3 activation decreases sensitivity of EGFR-mutant non-small cell lung cancer to icotinib.

Tyrosine kinase Inhibitors (TKIs) of epidermal growth factor receptor (EGFR) has considerably benefited for non-small cell lung carcinomas (NSCLC) harbor mutations in EGFR. However, the factors attenuating EGFR-TKI efficiency are obstacles to inhibit the proliferation of EGFR-mutant NSCLC cells successfully. Clarifying the insensitivity mechanisms of EGFR-TKI would help to develop new treatment strategy. In this study, the sensitivity of EGFR-mutant NSCLC cell lines, PC9 and HCC827, to icotinib was detected. Similar with other EGFR-TKIs such as gefitinib and erlortinib in previous research, the proliferation of two cell lines was apparently inhibited. However, we surprisingly found that contrast with the suppression of EGFR-AKT/ERK pathway, STAT3 was significantly activated in PC9 cells with the treatment of icotinib, but not in HCC827 cells. Further study confirmed that icotinib concomitantly induced IL-6 secretion and src activation in PC9 cells. Moreover, with the treatment of IL-6 neutralizing antibody or src inhibitor, dasatinib, icotinib-induced phosphorylation of STAT3 was reduced, as well as the sensitivity of PC9 to icotinib was also partially increased. Our results suggest that Src/IL-6/STAT3 bypass pathway is activated to maintain cell survival when the EGFR pathway was inhibited by TKIs, even in some EGFR-mutant NSCLC cells sensitive to TKIs. This finding provides a groundwork for potential combinatorial treatment with TKIs and Src or STAT3 inhibitor to improve icotinib sensitivity.

Temporal Trends of Common Female Malignances on Breast, Cervical, and Ovarian Cancer Mortality in Japan, Republic of Korea, and Singapore: Application of the Age-Period-Cohort Model.

BACKGROUND: Reproductive system cancer is an important cause of morbidity and mortality worldwide which threatens women's health and lives. Breast, cervical, and ovarian cancer have the higher incidence and mortality among a series of gynecology malignant tumor. We aimed to compare and assess the temporal trends of common female malignances on breast, cervical, and ovarian cancer mortality in developed regions of Asia including Japan, Republic of Korea, and Singapore and analyze the detached effects of chronological age, time period, and birth cohort by age-period-cohort (APC) analysis. METHODS: The mortality data for these three cancers were collected from the WHO Mortality Database in Japan, Republic of Korea, and Singapore from 1954 to 2013, from 1989 to 2013, and from 1964 to 2013, respectively. We fitted an age-period-cohort model and intrinsic estimator method to estimate the independent effect of each age, time period, and birth cohort on cancer mortality and describe the secular changes in three Asian countries. RESULTS: For the overall trends of breast cancer, the ASMRs of breast cancer showed a general increasing trend among three countries during the study periods while the change pattern in Singapore was different from the rest of the two countries for cervical and ovarian cancer. By APC analysis, the three cancer mortality risks generally increased with age and decreased with birth cohort. For period effects of breast and ovarian cancer, increasing effects with time were observed; however, for period effects of cervical cancer, converse change pattern was presented among three countries. CONCLUSIONS: Our study shows that the ASMRs of breast, cervical, and ovarian cancer remain high in Singapore compared to Japan and Korea. Generally speaking, the mortality risk of three cancers increased with age, and period and cohort effects may collectively affect the common female malignances mortality for East Asian women.

Non-invasive monitoring of in vivo degradation of a radiopaque thermoreversible hydrogel and its efficacy in preventing post-operative adhesions.

In vivo behavior of hydrogel-based biomaterials is very important for rational design of hydrogels for various biomedical applications. Herein, we developed a facile method for in situ fabrication of radiopaque hydrogel. An iodinated functional diblock copolymer of poly(ethylene glycol) and aliphatic polyester was first synthesized by coupling the hydroxyl end of the diblock copolymer with 2,3,5-triiodobenzoic acid (TIB) and then a radiopaque thermoreversible hydrogel was obtained by mixing it with the virgin diblock copolymer. A concentrated aqueous solution of the copolymer blend was injectable at room temperature and spontaneously turned into an in situ hydrogel at body temperature after injection. The introduction of TIB moieties affords the capacity of X-ray opacity, enabling in vivo visualization of the hydrogel using Micro-CT. A rat model with cecum and abdominal defects was utilized to evaluate the efficacy of the radiopaque hydrogel in the prevention of post-operative adhesions, and a significant reduction of the post-operative adhesion formation was confirmed. Meanwhile, the maintenance of the radiopaque hydrogel in the abdomen after administration was non-destructively detected via Micro-CT scanning. The reconstructed three-dimensional images showed that the radiopaque hydrogel with an irregular morphology was located on the injured abdominal wall. The time-dependent profile of the volume of the radiopaque hydrogel determined by Micro-CT imaging was well consistent with the trend obtained from the dissection observation. Therefore, the radiopaque thermoreversible hydrogel can serve as a potential visualized biomedical implant and this practical mixing approach is also useful for further extension into the in vivo monitoring of other biomaterials. STATEMENT OF SIGNIFICANCE: While a variety of biomaterials have been extensively studied, it is rare to monitor in vivo degradation and medical efficacy of a material after being implanted deeply into the body. Herein, the radiopaque thermoreversible hydrogel developed by us not only holds desirable performance on the prevention of post-operative abdominal adhesions, but also allows non-invasive monitoring of its in vivo degradation with CT imaging in a real-time, quantitative and three-dimensional manner. The methodology based on CT imaging provides important insights into the in vivo fate of the hydrogel after being deeply implanted into mammals for different biomedical applications and significantly reduces the amount of animals sacrificed.

Comparison of Secular Trends in Cervical Cancer Mortality in China and the United States: An Age-Period-Cohort Analysis.

Background: As one of the most common cancers in the female population, cervical cancer has ranked as the second most incident gynecological cancer in recent years, trailing only breast cancer. We aimed to assess and compare the secular trends in cervical cancer mortality in China and the United States and analyze the independent effects of chronological age, time period and birth cohort using age-period-cohort (APC) analysis. Methods: We performed an age-period-cohort analysis using the intrinsic estimator method to estimate the independent effects of age, time period, and birth cohort on cervical cancer mortality. We collected mortality data for China and the United States from the WHO Mortality Database and China Health Statistical Yearbook database. Results: We examined the general trends in cervical mortality rates in China and the United States during the periods 1988-2012 and 1953-2012, respectively. The age-standardized mortality rates (ASMRs) for cervical cancer in urban China, rural China and the U.S. showed a general decreasing trend during the observation period, except for urban China, which experienced a significant increase beginning in 2002. The mortality rates for cervical cancer in the three areas showed a general increasing trend with age, regardless of the period effect. Period effects declined steadily in both rural China (from 0.19 to -0.26) and the U.S. (from -0.20 to -0.43); however, a slight increasing trend was identified (from -0.25 to 0.33) in urban China, which indicated that the risk of mortality increased with time. Cohort effects peaked in the cohort born in 1911-1915 in both rural China and urban China, declined consistently in the cohort born before 1950, and then decreased again in the cohort born after 1976-1980. The cohort effect in the U.S. peaked in the birth cohort born in 1876-1880, then leveled off and slightly decreased in younger generations. Conclusions: Our study showed that in general, cervical cancer mortality rates increased with age and decreased with birth cohort in the U.S., while the risk of mortality was highest in the cohort born during 1946-1975 in urban China. Additionally, the risk of mortality consistently increased with age in women younger than 64 years old in urban and rural China and began to decline in older groups. Although the age and cohort effects were relatively strong, the period effect may be the key factor affecting cervical cancer mortality trends, mainly reflecting the immediate effects of effective treatment and the implementation of screening.

Secular Trends of Breast Cancer in China, South Korea, Japan and the United States: Application of the Age-Period-Cohort Analysis.

To describe the temporal trends of breast cancer mortality in East Asia and to better understand the causes of these trends, we analyzed the independent effects of chronological age, time period and birth cohort on breast cancer mortality trends using age-period-cohort (APC) analysis. We chose three main countries in East Asia, namely China, South Korea, and Japan, which have reported death status to the WHO Mortality Database, and used the United States as a comparison population. Our study shows that in general, breast cancer mortality rates in females increased in all three East Asian countries throughout the study period. By APC analysis, we confirmed that there is, in fact, a difference in age-specific mortality rate patterns between the Eastern and the Western countries, which is presumably caused by the two-disease model. While the cause of the decrease from approximately the 1950s generation is still in question, we believe that increasing general awareness and improvements in the health-care system have made a significant contribution to it. Although the age and cohort effects are relatively strong, the period effect may be a more critical factor in the mortality trend, mainly reflecting the increase in exposures to carcinogens and behavioral risk factors.