[Circ_0000263 improves radiosensitivity of Hela cells by inhibiting the activity of telomerase protein through miR-338-3p/TERT].

Objective: To explore the effect and molecular mechanism of circ_0000263 on HeLa cell activity, apoptosis, telomerase activity, and radiosensitivity. Methods: The Hela cells were divided into si-NC, si-circ, vector, circ_0000263, anti-NC, anti-miR-338-3p, miR-NC, miR-338-3p, si-circ+anti-NC, si-circ+ anti-miR-338-3p, si-circ+vector, si-circ+TERT, sh-NC, sh-circ groups. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expressions of circ_0000263 and miR-338-3p. Cell clone formation array was used to detect cell survival; cell counting kit-8 (CCK-8) to detect cell proliferation; flow cytometry to detect apoptosis; western blot method to detect the expressions of proliferating cell nuclear antigen (PCNA), Cleaved-casp3, telomerase reverse transcriptase (TERT) proteins; double luciferase assay to detect the targeting relationships of circ_0000263 and miR-338-3p, miR-338-3p and TERT; telomere repeat amplification enzyme linked immunosorbent assay (TRAR-ELISA) to detect telomerase activity. Results: Circ_0000263 was highly expressed in Hela cells, miR-338-3p was low expressed, and TERT was highly expressed; circ_0000263 was also highly expressed in Hela cells treated with radiation (P＜0.05). Knockdown of circ_0000263 inhibited the clone formation and cell proliferation ability of HeLa cells, and enhanced the radiosensitivity and apoptosis of HeLa cells. In contrast, knockdown of circ_0000263 decreased PCNA protein expression level and enhanced Cleaved-casp3 protein expression level in HeLa cells (P＜0.05). The apoptosis rate in the si-circ group was (13.19±1.12)%, which was higher than (6.80±0.62)% of si-NC group (P＜0.05). The apoptosis rate in the si-circ+4 Gy group was (24.82±1.57)%, which was higher than (17.00±0.96)% of si-NC+4 Gy group (P＜0.05). Circ_0000263 targeted regulated miR-338-3p, and miR-338-3p targeted regulated TERT. MiR-338-3p was lowly expressed in HeLa cells, and knockdown of circ_0000263 elevated miR-338-3p expression level in HeLa cells. Circ_0000263 regulated TERT expression and inhibited telomerase activity through miR-338-3p. MiR-338-3p/TERT can restore the effect of circ_0000263 on the radiosensitivity of Hela cells. The apoptosis rate in the si-circ+anti-NC group was (27.37±0.89)%, which was higher than (18.22±1.18)% of the si-circ+anti-miR-338-3p group (P＜0.05). The apoptosis rate in the si-circ+vector group was (27.55±0.48)%, which was higher than (20.10±0.68)% of si-circ+TERT group (P＜0.05). After 72 hours of radiation by 4 Gy, the cell survival fraction of si-circ+anti-NC group was 0.41±0.02, which was lower than 0.66±0.03 of the si-circ+anti-miR-338-3p group (P＜0.05); the cell survival fraction of si-circ+vector group was 0.42±0.05, which was lower than 0.70±0.03 of si-circ+TERT group (P＜0.05). Conclusion: Inhibiting the expression of circ_0000263 supresses the proliferation of Hela cells by regulating miR-338-3p/TERT, promotes apoptosis, inhibits telomerase activity, increases the radiosensitivity of cancer cells, and provides a theoretical basis for improving the radiosensitivity of Hela cells.

[Long-term health-related quality of life and related factors in children with severe hemophilia A who received regular low-dose prophylaxiss].

Objective: To investigate long-term health-related quality of life (HRQoL) and related factors in children with severe hemophilia A (HA) who received regular low-dose prophylaxis. Methods: Clinical data of severe HA children who began to receive regular low-dose coagulation factor Ⅷ (FⅧ) prophylaxis in Peking Union Medical College Hospital from January 1, 2008 to December 31, 2011 were retrospectively enrolled. The longest last follow-up period was May 31, 2023. The attendance of school or work and daily physical activity during the last follow-up were investigated. The patients were divided into full attendance group and incomplete attendence group according to attendance. The patients were divided into into exercise attainment group (reached Chinese sports recommendation) and exercise nonattainment group according to the exercise status. Barthel score was used to assess activities of daily living and Haemo-QoL was used to assess quality of life. Long-term HRQoL for children aged 8-16 years and patients aged 17 years and above were assessed using Haemo-QoL SF and Haem-A-QoL versions, respectively. Spearman correlation analysis was used to examine the correlation between treatment conditions and Haemo-QoL scores. Results: A total of 22 cases were enrolled, the prophylaxis initiation age ranged from 1.8-17.9 (10.4±3.8) years old. The average prophylactic FⅧ dose during low-dose prophylaxis was 24.2 U/kg per week and the follow-up time was 6.3-15.1 (9.6±2.8) years. At the last follow-up, the age of the patients was (20.2±5.4) years, of which 14 (63.6%) were adults over 18 years old. There were 15 patients in the full attendance group and 7 patients in the incomplete attendence group. Compared with the full attendance group, the incomplete attendence group had a smaller preventive treatment dose [M(Q1, Q3), (28.4±11.1) vs (15.3±3.7) U/kg, P=0.012], shorter preventive treatment time [148. 1 (18.6, 346.5) vs 48.0 (32.0, 156.9) weeks, P=0.017], and higher annual joint bleeding rate (AJBR) [12.5 (6.0, 22.3) vs 14.2 (13.2, 17.8) times, P=0.017]. There were 7 cases in the exercise attainment group and 15 cases in the exercise nonattainment group. Compared to the exercise attainment group, the exercise nonattainment group had shorter preventive treatment time[313. 7 (156.9, 366.0) vs 48.0 (16.5, 108.9) weeks, P=0.006], a higher AJBR [7.0 (5.1, 10.0) vs 23.3 (12.5, 29.8), P=0.003] and a higher hemophilia joint health score (HJHS) [9.0 (2.0, 15.5) vs 23.0 (12.0, 27.8), P=0.014]. Barthel score showed 81.8% (18 cases) of the patients' living ability was not influenced by the illness. In Haemo-QoL score, the total score of Haemo-QoL SF in 7 cases was (47.6±17.0) scores, the total score of Haem-A-QoL in 15 cases was (45.2±22.6) scores. The daily activity dimension of the Haem-A-QoL score was the lowest [38.2 (10.9, 45.5) scores], which was positively correlated with the starting age of prophylactic initiation (r=0.501, P=0.057), and negatively correlated with the duration of prophylaxis (r=-0.545, P=0.036). Conclusions: Regular low-dose prophylaxis could improve the long-term HRQoL of some children with severe HA, and children with higher prophylactic doses and longer prophylactic treatment time have higher quality of life.

[Establishment and validation of a prediction model for early-stage epithelial ovarian cancer based on LASSO regression].

Objective: To establish and validate a prediction model for early-stage epithelial ovarian cancer based on least absolute shrinkage and selection operator (LASSO) regression. Methods: A total of 509 cases ovarian mass patients who underwent surgical treatment in Tianjin Medical General Hospital from January 2018 to March 2023 were retrospectively analyzed. The patients were randomly divided into modeling group [n=356, M(Q1,Q3) for age were 43 (31, 61) years] and internal validation group [n=153, age 42 (31, 60) years] by 7∶3 ratio. In addition, 86 patients [age 44 (33, 61) years] who underwent surgical treatment for ovarian mass in Tianjin Medical University General Hospital from April to November 2023 were collected as external validation group. The variables were screened by LASSO regression. The nomogram model was established and plotted by multivariate logistic regression. Internal and external validation were then conducted. The model performance and clinical applicability were evaluated using receiver operating characteristic (ROC) curve, calibration curve and decision curve. Results: Five variables including age (OR=1.040,95%CI:1.000-1.050,P=0.002), carbohydrate antigen 125 (CA125) (OR=1.001, 95%CI: 1.000-1.010, P=0.017), human epididymis protein 4 (HE4) (OR=1.020, 95%CI: 1.000-1.030, P=0.002), carbohydrate antigen 199 (CA199) (OR=1.001, 95%CI:1.000-1.020, P=0.023) and lactate dehydrogenase (LDH) (OR=1.020, 95%CI: 1.010-1.022, P=0.001) were screened as risk factors for early-stage epithelial ovarian cancer. The nomogram model was constructed based on these above five risk factors to predict early-stage epithelial ovarian cancer. ROC curves showed the area under curve (AUC) were 0.915(95%CI:0.910-0.932)for modeling group, 0.891(95%CI:0.874-0.905) for internal validation group, and 0.924(95%CI:0.907-0.942) for external verification. The calibration curves and clinical decision curves showed the model exhibited good consistency and clinical practicability. Conclusions: The nomogram model built includes age, CA125, HE4, CA199, and LDH. It can effectively predict early-stage epithelial ovarian cancer and has strong clinical practicability.

[Precision nutritional therapy in gastrointestinal tumor].

Apart from individual genetic background, unhealthy lifestyle and diet, etc., nutrition also plays an important role in the occurrence and progression of gastrointestinal tumors. Although some patients with gastrointestinal tumors can be satisfied with the traditional nutritional support, it is apparently inadequate for the systemic management of all patients. Precision nutrition support, also known as personalized nutrition support, refers to safe and efficient individualized nutrition intervention based on the investigation of individual genetic background, life characteristics, metabolic indicators, intestinal microbial characteristics, and physiological status factors through big data analysis for the prevention and treatment of chronic diseases. This review focuses on the relationship between nutrition and gastrointestinal tumors and discusses the progress of precision nutrition support therapy in the gastrointestinal tumors. Based on this, we hope to achieve effective personalized intervention protocols, and improve the clinical outcome and the overall oncology care of gastrointestinal tumors.

[Efficacy of different regimens and prognostic factors in patients with first relapsed multiple myeloma treated after front-line bortezomib, cyclophosphamide, and dexamethasone].

Objective: To analyze the efficacy of second-line regimens and prognostic factors in patients with first-relapsed multiple myeloma (MM) treated with bortezomib, cyclophosphamide, and dexamethasone (BCD). Methods: A retrospective cohort study. Clinical data were collected in first-relapsed MM patients after BCD treatment from three tertiary hospitals in north China from July 2009 to October 2022. Patients were classified according to the second-line regimen into the immunotherapy group, single novel agent group [either proteasome inhibitor (PI) or immunomodulatory drug (IMiD)], combination treatment group (both PI+IMiD), and traditional treatment group. Responses to second-line regimens and survival data were analyzed. The Kaplan-Meier method was used for survival analysis and the Cox proportional risk model was used for univariate and multivariate analyses. Results: A total of 217 patients were enrolled including 8.8% (19/217) in the immunotherapy group, 48.4% (105/217) in the PI/IMiD group, 29.9% (65/217) in the PI+IMiD group, and 12.9% (28/217) in the traditional treatment group. The median age was 62 years (range 31-83 years) and 56.2% (122/217) were males. The overall response rates (ORRs) in the four groups were 94.7% (18/19) vs. 56.2% (59/105) vs. 73.8% (48/65) vs. 32.1% (9/28) (χ2=24.55; P<0.001), respectively. The progression-free survival (PFS) of the second-line regimens (2ndPFS) was 17.7 vs. 9.0 vs. 9.2 vs. 4.6 months (χ2=22.74; P<0.001), respectively, among which patients in the PI/IMiD and PI+IMiD groups had comparable 2ndPFS (χ2=1.76; P=0.923). Patients with high-risk cytogenetic abnormalities (HRCAs) achieved the longest 2ndPFS of 22.0 months in the immunotherapy group (χ2=15.03; P=0.002). Multivariate analysis suggested that immunotherapy (HR=0.11, 95%CI 0.05-0.27), achievement of efficacy of partial response or better (HR=0.47, 95%CI 0.34-0.66), and non-aggressive relapse (HR=0.25, 95%CI 0.17-0.37) were independent prognostic factors of 2ndPFS. Conclusion: In this real-world study, immunotherapy was associated with a more favorable efficacy and PFS for first-relapsed MM patients after BCD treatment, with similar outcomes in patients with HRCAs.

[Animal study on left bundle branch current of injury and anatomic location of leads in His-purkinje conduction system pacing].

Objective: Explore the relationship between tip of the left bundle branch pacing lead and anatomic location of left bundle branch as well as the mechanism of left bundle branch current of injury. To clarify the clinical value of left bundle branch current of injury during operation. Methods: The pacing leads were implanted in the hearts of two living swines. Intraoperative electrophysiological study confirmed that the left bundle branch or only the deep left ventricular septum was captured at low output. Immediately after operation, the gross specimen of swine hearts was stained with iodine to observe the gross distribution of His-purkinje conduction system on the left ventricular endocardium and its relationship with the leads. Subsequently, the swine hearts were fixed with formalin solution, and the pacing leads were removed after the positions were marked. The swine hearts were then sectioned and stained with Masson and Goldner trichrome, and the relationship between the anatomic location of the conduction system and the tip of the lead was observed under a light microscope. Results: After iodine staining of the specimen, the His-purkinje conduction system was observed with the naked eye in a net-like distribution, and the lead tip was screwed deeply and fixed in the left bundle branch area of the left ventricular subendocardium in the ventricular septum. Masson and Goldner trichrome staining showed that left bundle branch pacing lead directly passed through the left bundle branch when there was left bundle branch potential with left bundle branch current of injury, while it was not directly contact the left bundle branch when there was left bundle branch potential without left bundle branch current of injury. Conclusion: The left bundle branch current of injury observed on intracardiac electrocardiogram during His-purkinje conduction system pacing suggests that the pacing lead directly contacted the conduction bundle or its branches, therefore, the captured threshold was relatively low. Left bundle branch current of injury can be used as an important anatomic and electrophysiological evidence of left bundle branch capture.

[Remodeling of tumor stroma combined with photothermal therapy in the treatment of triple-negative breast cancer].

Objective: Polyethylene glycol-modified gold nanostar particles (GNS-PEG) were constructed to investigate whether the degradation of extracellular matrix in triple-negative breast cancer could improve the tumor delivery of GNS-PEG and enhance the efficacy of photothermal therapy. Methods: GNS-PEG were constructed and characterized for physicochemical properties as well as photothermal properties. At the cellular level, the cytotoxicity of halofuginone (HF) and the effect of photothermal therapy were detected. Mouse model of triple negative breast cancer was established by subcutaneous inoculation of 4T1 cells in BALB/c nude mice. Five injections of HF were given via tail vein (HF group), and tumor sections were stained with Masson stain and immunohistochemical staining for transforming growth factor ß1 (TGFß1), α-smooth muscle actin (α-SMA) and CD31 to observe the effect of tumor stromal degradation. Five injections of HF via tail vein followed by GNS-PEG (HF+ GNS-PEG group) were applied to determine the content of gold in tumor tissues by inductively coupled plasma mass spectrometry. The tumor sites of the mice in the GNS-PEG and HF+ GNS-PEG groups were irradiated with NIR laser and the temperature changes were recorded with an IR camera. The tumour growth and weight changes of mice in each group were observed. Ki-67 immunohistochemical staining, TdT-mediated dUTP nick-end labeling and HE staining were performed on tumor tissue sections from each group to observe tumor proliferation, apoptosis and necrosis. HE staining was performed on heart, liver, spleen, lung and kidney tissues from each group to observe the morphological changes of cells. Results: GNS-PEG nanoparticles showed a multi-branched structure with a particle size of 73.5±1.4 nm. The absorption peak of GNS was 810 nm, which is in the near infrared region. The photothermal conversion rate of GNS-PEG was up to 79.3%, and the photothermal effect could be controlled by the laser energy. HF has a concentration-dependent cytotoxicity, with a cell survival rate being as low as (22.8±2.6)% at HF concentration of up to 1 000 nmol/L. The photothermal effect of GNS-PEG was significant in killing tumor cells, with a cell survival rate of (32.7±5.2)% at the concentration of 25 pmol/L. The collagen area fraction, TGFß1 integrated optical density and α-SMA integrated optical density in the tumor tissues of mice in the HF group were (2.1±0.2)%, 3.1±0.4 and 5.2±1.9, respectively, which were lower than those of the control group (all P<0.01), and the vessel diameter was 8.6±2.9 µm, which was higher than that of the control group (P<0.05). In the HF+ GNS-PEG group, the concentration of gold in tissues was 52.4 µg/g, higher than that in the GNS-PEG group (15.9 µg/g, P<0.05). After laser irradiation, the temperature of the tumor site in the HF+ GNS-PEG group was significantly higher than that in the GNS-PEG group. At the 4th minute, the temperatures of the tumor site in the GNS-PEG and HF+ GNS-PEG groups were 51.5 ℃ and 57.7 ℃ respectively; the tumor volume in the HF+ GNS-PEG group was effectively suppressed. The body weights of the mice in each group did not change significantly during the monitoring period. No significant abnormalities were observed in the main organs of the mice in the GNS-PEG group, but some hepatocytes in the HF and HF+ GNS-PEG groups showed edema and degeneration. Conclusion: The remodeling of extracellular matrix in triple-negative breast cancer could significantly improve the intratumoral delivery of GNS-PEG and thus achieve better photothermal therapy effect.

[A cross-sectional survey on the allocation of nursing human resources in burn centers in China].

Objective: To investigate the allocation of nursing human resources in burn centers in China. Methods: A cross-sectional survey was conducted. Using a self-designed questionnaire, a survey was carried out from January to March 2022 to investigate the January to December 2021 status of 39 burn centers in China that met the inclusion criteria based on six strategic regions and other regions, including the hospital grade and the region, the number of nurses and opening beds in the burn centers and burn intensive care units (BICUs), the age, working seniority in burn specialty, educational background, professional title, personnel employment, and turnover of nurses and training of newly recruited nurses in the burn centers. Results: This survey covered 30 provinces, municipalities, and autonomous regions in China (excluding Hong Kong Special Administrative Region, Macao Special Administrative Region, and Taiwan region of China). A total of 39 questionnaires were collected, all of which were valid. The 39 burn centers were located in 38 tertiary A hospitals and 1 tertiary B hospital, with 26 burn centers in strategic areas. The nurse/bed ratio of burn centers in the Greater Bay Area of Guangdong, Hong Kong, and Macao was the highest, while the nurse/bed ratio of burn centers in border ethnic minority area was the lowest. Except for the Chengdu-Chongqing Economic Circle, BICUs had been set up in burn centers in other regions. Among the 39 burn centers, the percentage of nurses aged 25 to 34 years was 51.21% (738/1 441), the percentage of nurses worked in burn specialty for less than 5 years was 31.16% (449/1 441), the percentage of nurses with bachelor's degree was 69.74% (1 005/1 441), and the percentage of nurses with nursing professional title was 44.14% (636/1 441), which were the highest. There were significant differences in the employment of nurses, the percentage of permanent nurses in burn centers in the collaborative development zone of Beijing-Tianjin-Hebei was 82.48% (113/137), while the percentage of permanent nurses in burn centers in important military strategic area was only 9.42% (34/361); the turnover rate of nurses was 9.03% (143/1 584), among which the turnover rate of nurses was 18.14% (80/441) in burn centers in important military strategic area. The training for newly recruited nurses in 39 burn centers was mainly based on the guidance of senior nurses and the pre-job education+specialist training. Conclusions: The burn nursing human resources in strategic areas in China are seriously insufficient and unevenly distributed, with unstable nurse team and lack of standardized specialist training. In particular, the nursing human resources in BICUs need to be equipped and supplemented urgently.

[Analysis of changes in reporting and diagnosis of pulmonary tuberculosis among children in Liangshan Yi Autonomous Prefecture, Sichuan Province from 2019 to 2021].

Objective: To compare the characteristics of children's pulmonary tuberculosis (PTB) cases reported from 2019 to 2021 before and during the implementation of the Action Plan to Stop Tuberculosis. Methods: Based on the reported incidence data and population data of child pulmonary tuberculosis (PTB) notified to the Chinese Center for Disease Control and Prevention (CDC) Tuberculosis Information Management System (TBIMS) from 2019 to 2021, the population information and clinically relevant information in different years were compared. Results: From 2019 to 2021, the reported cases of PTB in children were 363, 664 and 655, respectively. The number of reported cases increased significantly. The median age of the cases in children increased from 10.4 years in 2019 to 11.7 years in 2021 (P=0.005) over a three-year period. The etiological positive rate increased significantly from 11.6% (42/363) in 2019 to 32.2% (211/655) in 2021 (P<0.001). The positive rate of molecular testing increased most significantly, which became the main means of etiological detection and accounted for 16.7% (7/42), 62.0% (57/92) and 75.4% (159/211) of the children with positive etiological results, respectively. The resistance rates of isoniazid and rifampicin were analyzed in children with PTB who underwent drug sensitivity tests. The results showed that the resistance rates of isoniazid and/or rifampicin were 2/9, 3.9% (2/51) and 6.7% (11/163), respectively, with an average of 6.7% (15/223) over three years. The median patients' delay was 27 (12, 49) days in 2019. It was reduced to 19 (10, 37) days in 2020 and 15 (7, 34) days in 2021, both significantly lower than 2019 (P=0.009 and 0.000 2, respectively). Conclusion: From 2019 to 2021, the reported numbers of children with PTB and children with positive etiological results increase significantly in Liangshan Prefecture, while the diagnosis delay of patients significantly reduces.

[Study on the reliability and validity of the Chinese Criteria of Health Scale for the elderly people].

Objective: To evaluate the reliability and validity of the Chinese Criteria of Health Scale for the elderly people. Methods: A cross-sectional study was performed among older adults of Meiyuan Community in Haidian District, Beijing and Nanwangkong Village in Qingzhou City,Shandong Province during July 2021. Using a cluster sampling method, totally 667 elderly people were investigated by face-to-face interview, using the scale which was formulated after two rounds of the Delphi method and pilot study. The overall scale includes physical health, mental health and social health subscales, including 9, 52 and 15 items, respectively. Four weeks after the survey, 56 elderly people were randomly selected and repeated the survey with the same method. The test-retest reliability, split-half reliability and internal consistency reliability of the scale were evaluated, and the validity was evaluated at the same time, including construct validity and content validity. Results: A total of 710 questionnaires were distributed and 667 valid questionnaires were obtained, with a total effective rate of 93.94%. The score of the overall scale was 79.79±16.22, the scores of the physical health, mental health, social health sub-scores were 41.64±9.76, 26.82±3.92 and 11.34±5.19, respectively. The scale had excellent reliability. In the test-retest reliability, the intraclass correlation coefficient (ICC) of the overall scale and each subscale were 0.766-0.861, and the weighted Kappa values were 0.762-0.817. The Spearman-Brown coefficient of the overall scale and each subscale in the split-half reliability were 0.722-0.855 (all P<0.001). The Cronbach's α coefficients of the overall scale of internal consistency reliability and each subscale were 0.748-0.899, and the Cronbach's α coefficients of each dimension were from 0.709 to 0.963(all P<0.001). At the same time, the scale had good construct validity and content validity. The correlation coefficients between the score of each dimension and its sub-scale were larger, from 0.641 to 0.873 (all P<0.05). The cumulative variance contribution rates of the scale and three subscales were all more than 50% of the approved standard. A total of 11 common factors were extracted, and all the load values of each item on the corresponding factors were ≥0.04. Conclusion: The Chinese Criteria of Health Scale for the elderly people has good validity and excellent reliability. It can be used as a basis for the scientific division of the health status of the elderly, the formulation of relevant policies by the government and the provision of appropriate health services for the elderly.

Long-term use of Lacticaseibacillus paracasei N1115 from early life alleviates high-fat-diet-induced obesity and dysmetabolism in mice.

Obesity has become one of the most serious public health problems worldwide, and an increasing number of studies indicate that the gut microbiota can affect host metabolism. Therefore, the present study was conducted to evaluate whether long-term use of probiotics can alleviate host obesity and metabolism by altering gut microbiota. The high-fat diet (HFD) starting from weaned period led to higher levels of visceral fat and a significantly heavier liver in male mice. Moreover, HFD resulted in disorders of glucose and lipid metabolism, changes in insulin-resistance indices (IR), and an increase in serum insulin and leptin in mice. Of note, 15 weeks use of Lacticaseibacillus paracasei N1115 decreased visceral fat, liver weight, serum levels of insulin and leptin, and IR and alleviated lipid dysmetabolism. HFD resulted in a significant increase in the relative abundance of Bilophila, Lachnoclostridium, and Blautia and may decrease the faecal short-chain fatty acid (SCFA) levels in mice; in turn, treatment with the potential probiotic strain L. paracasei N1115 protected mice from these negative effects. HFD significant impaired the physiology of the host especially in male mice and dramatically changed the composition of host gut microbiota. However, the use of potential probiotic strain, such as L. paracasei N1115, may prevent these impairments due to HFD via effecting the host gut microbiota and SCFA.

[Blocking PAK1 kinase activity promotes the differentiation of acute megakaryocytic leukemia cells and induces their apoptosis].

Objective: To investigate the effect of blocking P21 activated kinase 1 (PAK1) activity on the proliferation, differentiation, and apoptosis of acute megakaryocytic leukemia (AMKL) cell lines (CHRF and CMK) . Methods: Cell counts were used to detect the effects of PAK1 inhibitors (IPA-3 and G5555) on AMKL cell proliferation inhibition and colony formation, and flow cytometry was used to detect its effects on AMKL cell cycle. The effect of PAK1 inhibitor on the expression of cyclin D1 and apoptosis-related protein Cleaved caspase 3 was detected using Western blot, while interference with the protein expression level of PAK1 in AMKL cells was assessed using lentivirus-mediated shRNA transfection technology. Flow cytometry was used to detect the effects of knockdown of PAK1 kinase activity on the ability of polyploid DNA formation and cell apoptosis in AMKL cells. Results: PAK1 inhibitors inhibited the proliferation of AMKL cells in a dose-dependent manner and reduced the ability of cell colony formation, and the difference was statistically significant when compared with the control group (P<0.05) . Moreover, they also reduced the percentage of AMKL cells in S phase, and Western blot detection showed that the expression levels of phosphorylated PAK1 and cyclin D1 decreased significantly. Finally, PAK1 inhibitors induced AMKL cell apoptosis by up-regulating Cleaved caspase 3 and showed different abilities to increase the content of polyploid DNA in megakaryocytes. Only high concentrations of IPA-3 and low doses of G5555 increased the number of polyploid megakaryocytes, while knockdown of PAK1 kinase activity promoted AMKL cell differentiation and increased the apoptosis rate. Conclusion: PAK1 inhibitor significantly arrests AMKL cell growth and promotes cell apoptosis. Knocking down the expression of PAK1 promotes the formation of polyploid DNA and induces AMKL cell apoptosis. The above findings indicate that inhibiting the activity of PAK1 may control AMKL effectively.

Using transvaginal ultrasonography and MRI to evaluate ovarian volume and follicle count of infertile women: a comparative study.

AIM: To compare two-dimensional (2D) transvaginal ultrasonography (TVUS) and 2D/three-dimensional (3D) magnetic resonance imaging (MRI) in estimating ovarian volume and follicle count. MATERIALS AND METHODS: The ovarian volume (OV) and follicle count (FC) of 84 women with infertility were evaluated by 2D TVUS and 2D/3D MRI. Bland-Altman analysis was used for comparison. RESULTS: The OV from 3D MRI was 0.50 ml (95% confidence interval [CI], 0.25-0.74, p<0.001) smaller than that by 2D TVUS. OV from 2D MRI was 2.65 ml (95% CI, 2.36-2.95, p<0.001) and 3.15 ml (95% CI, 2.77-3.53, p<0.001) smaller than that from 3D MRI and 2D TVUS, respectively. The FC1-9 mm and total follicle count (tFC) estimated by 2D TVUS were 7.81 (95% CI, 6.96-8.66, p<0.001) and 7.82 (95% CI, 6.97-8.67) smaller than those from 2D MRI, respectively. Further analysis showed that 2D TVUS detected lower FC1-3 mm but higher FC4-6 mm than 2D MRI. No significant difference was shown in the results of FC7-9 mm and FC ≥ 10 mm. CONCLUSION: In women with infertility, 2D MRI underestimated OV as compared with 2D TVUS. OV from 3D MRI was lower but very close to that from 2D TVUS. For patients unsuitable for TVUS, 3D MRI is recommended for OV evaluation. 2D TVUS underestimated FC1-9 mm and tFC compared with 2D MRI. In fertility counselling and research, 2D MRI is a useful alternative to TVUS when an accurate FC is needed.

[The function of auditory cortex in the elderly using functional near-infrared spectroscopy technology].

Objective: Functional near-infrared spectroscopy (fNIRS) was used to study the effect of aging on the neuroimaging characteristics of cerebral cortex in the process of speech perception. Method: Thirty-four adults with normal hearing were recruited from March 2021 to June 2021, including 17 in the young group, with 6 males, 11 females, age (32.1±5.0) years, age range 20-39 years. and 17 in the elderly group, with 6 males, 11 females, age (63.2±2.8) years, age range 60-70 years. The test material was the sentence table of the Mandarin Hearing Test in Noise (MHINT). The task state block experiment design was adopted, and the temporal lobe, Broca's area, Wernicke's area, motor cortex were used as regions of interest. Objective brain imaging technology (fNIRS) combined with subjective psychophysical testing method was used to analyze the activation area and degree of cerebral cortex related to auditory speech perception in the elderly and young people under different listening conditions (quiet, signal-to-noise ratio of 10 dB, 5 dB, 0 dB, -5 dB). SPSS 23 software was used for statistical analysis. Result: The activation area and degree of activation in the elderly group were lower than those in the young group under each task condition; The number of activation channels in the young group were significantly more than those in the old group, and the number of activation channels in the left hemisphere were more than those in the right hemisphere, but there was no difference in the number of activation channels. There were more channels affected by age in the left hemisphere than in the right hemisphere. The activation degree of the young group when the signal-to-noise ratio was 0 dB was significantly higher than that of other signal-to-noise ratio conditions (P<0.05), but there was no significant difference in the old group under the five conditions (P>0.05). The speech recognition score of the young group was higher than that of the old group under all conditions. When the quiet and signal-to-noise ratio was 10 dB, the correct score of the two groups was equal or close to 100%. With the gradual decrease of signal-to-noise ratio, there was a significant difference between the two groups when the signal-to-noise ratio was 5 dB. The speech recognition accuracy of the young group decreased significantly when the signal-to-noise ratio was 0 dB, while that of the old group decreased significantly when the signal-to-noise ratio was 5 dB. Conclusions: With the increase of age, the speech perception in noisy environment and the activity of cerebral cortex gradually deteriorate, and the speech dominance hemisphere (left hemisphere) will be significantly affected by aging. The overall activation area and activation degree of the elderly under different speech tasks are lower than those of the young.

Vitamin D inadequacy combined with high BMI affects paraspinal muscle atrophy and pain intensity in postmenopausal women.

OBJECTIVE: This study was performed to assess the effects of vitamin D deficiency/insufficiency combined with a high body mass index (BMI) on paraspinal muscle (PSM) atrophy and pain intensity in postmenopausal women with lower back pain (LBP). METHODS: In total, 365 postmenopausal women were analyzed in the study. We divided the women into four groups according to BMI and vitamin D status. Outcome measurements included PSM atrophy, fatty infiltration (FI) and severity of LBP. Binary logistic regression was used to analyze the odds ratio (OR), and the interaction between the BMI and vitamin D status was tested. RESULTS: Compared with the control group, the high BMI with vitamin D deficiency/insufficiency group had a significantly increased risk of FI > grade 2 (OR = 10.69, p < 0.001), hand grip strength of <16 kg (OR = 8.96, p < 0.001), Short Physical Performance Battery score of ≤8 (OR = 3.69, p < 0.001) and visual analog scale (VAS) score of >3 (OR = 4.76, p < 0.001). A significant positive additive interaction was found between the BMI and vitamin D status on PSM atrophy. CONCLUSION: Vitamin D deficiency/insufficiency combined with a high BMI was associated with PSM atrophy and LBP intensity in postmenopausal women. The interaction analysis showed a positive additive interaction between BMI and vitamin D status.