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Background: Nasopharyngeal carcinoma (NPC) is a malignant tumor with poor survival rate. G2 and S phase-expressed‐1 (GTSE1) takes part in the progression of diverse tumors as an oncogene, but its role and potential mechanism in NPC remain unknown. Methods: The GTSE1 expression was analyzed by western blot in NPC tissues and cells. Knock-down experiments were conducted to determine the function of GTSE1 in NPC by cell counting kit-8, the 5-ethynyl-2′-deoxyuridine (EdU) incorporation experiment, cell scratch wound-healing experiment, transwell assays, tube forming experiment and western blot. In addition, the in vivo role of GTSE1 was addressed in tumor-bearing mice. Results: The expression of was increased in NPC. Silencing of GTSE1 suppressed cell viability, the percent of EdU positive cells, and the number of invasion cells and tubes, but enhanced the scratch ratio in NPC cells. Mechanically, downregulation of GTSE1 decreased the expressions of FOXM1 and STMN1, which were restored with the upregulation of FOXM1. Increased expression of STMN1 reversed the effects of the GTSE1 silencing on proliferation, migration, invasion and angiogenesis of NPC cells. Furthermore, knockdown of GTSE1 repressed the tumor volume and tumor weight of xenografted mice. Conclusion: GTSE1 was highly expressed in NPC, and silencing of GTSE1 ameliorated the malignant processes of NPC cells by upregulating STMN1, suggesting a possible therapeutical target for NPC. [ABSTRACT FROM AUTHOR]

Background: Thin endometrium is considered suboptimal for embryo implantation, leading to compromised pregnancy rates without effective therapies. While some studies have reported promoted endometrial growth after a period of hyperbaric oxygen therapy (HBOT) in patients with intrauterine adhesion, there have been no reports in patients with resistant thin endometrium. The purpose of this study was to investigate the impact of HBOT on endometrium growth and pregnancy outcomes in patients with resistant thin endometrium during frozen embryo transfer (FET) treatments. Methods: This prospective pre-post cohort study was conducted at a university-affiliated assisted reproductive medical center between October 2021 and December 2022. Patients who had experienced at least one canceled transfer cycle due to a thin endometrium(< 7 mm) on the endometrium transformation day, despite the use of standard therapies as well as adjuvant therapies, were enrolled in the study. Patients were assigned voluntarily to either the HBOT group or the concurrent control group. The HBOT group received daily HBOT for at least 10 days during the proliferative phase, in addition to the routine endometrium preparation methods and the concurrent control group underwent cycles without HBOT. Propensity score matching (PSM) was used to ensure comparability between the groups. Both self-control and case-control comparisons were conducted. The primary outcome measured was endometrial thickness (ET) on the day of endometrium transformation. Secondary outcomes included intrauterine pregnancy rate (IPR), embryo implantation rate (IR), miscarriage rate, and others. Results: Patients in the HBOT group demonstrated a significantly thicker endometrial thickness on the day of endometrium transformation after undergoing therapy (5.76 ± 1.66 vs. 6.57 ± 1.23, P = 0.002). This improvement was accompanied by a decreased rate of cycle cancellations. Baseline parameters and endometrial thickness were comparable between the HBOT group and the concurrent control group during the cycle. The IPR was similar in patients who received cleavage-stage embryos (0.0% vs. 6.7%, P = 1.00), but significantly higher in patients in the HBOT group who received blastocysts (53.8% vs. 18.2%, P = 0.017). Conclusions: A period of HBOT prior to endometrium transformation contributes to increased endometrial thickness and facilitates blastocyst implantation in patients with resistant thin endometrium during FET treatments. Trial registration: The trial was registered on the Chinese Clinical Trial Registry (registration no. ChiCTR2300072831, retrospectively registered). [ABSTRACT FROM AUTHOR]

The Bacillus Calmette-Guérin (BCG) vaccine was discovered a century ago and has since been clinically applicable. BCG can not only be used for the prevention of tuberculosis, but also has a non-specific protective effect on the human body called trained immunity that is mediated by innate immune cells such as monocytes, macrophages, and natural killer cells. Mechanisms of trained immunity include epigenetic reprogramming, metabolic reprogramming, and long-term protection mediated by hematopoietic stem cells. Trained immunity has so far shown beneficial effects on cancer, viral-infections, autoimmune diseases, and a variety of other diseases, especially bladder cancer, respiratory viruses, and type 1 diabetes. The modulation of the immune response by BCG has led to the development of a variety of recombinant vaccines. Although the specific mechanism of BCG prevention on diseases has not been fully clarified, the potential role of BCG deserves further exploration, which is of great significance for prevention and treatment of diseases. [ABSTRACT FROM AUTHOR]

Background: Carbapenem-resistant Enterobacter cloacae complex (CREC) is a new emerging threat to global public health. The objective of the study was to investigate the clinical characteristics and molecular epidemiology of CREC infections in the medical center of northeast China.Methods: Twenty-nine patients were infected/colonized with CREC during a ten-year period (2010-2019) by WHONET analysis. Antibiotic susceptibilities were tested with VITEK 2 and micro broth dilution method (for polymyxin B and tigecycline). Carbapenemase encoding genes, β-lactamase genes, and seven housekeeping genes for MLST were amplified and sequenced for 18 cryopreserved CREC isolates. Maximum likelihood phylogenetic tree was built with the concentrated sequences to show the relatedness between the 18 isolates.Results: There was a rapid increase in CREC detection rate during the ten-year period, reaching 8.11% in 2018 and 6.48% in 2019. The resistance rate of CREC isolates to imipenem and meropenem were 100.0 and 77.8%, however, they showed high sensitivity to tigecycline, polymyxin B and amikacin. The 30-day crude mortality of CREC infection was 17.4%, indicating that it may be a low-virulence bacterium. Furthermore, molecular epidemiology revealed that ST93 was the predominant sequence type followed by ST171 and ST145, with NDM-1 and NDM-5 as the main carbapenemase-encoding genes. Moreover, E. hormaechei subsp. steigerwaltii and E. hormaechei subsp. oharae were the main species, which showed different resistance patterns.Conclusion: Rising detection rate of CREC was observed in a tertiary hospital, which showed heterogeneity in drug resistance patterns, resistance genes, and MLST types. Effective infection prevention and control measures should be taken to reduce the spread of CREC. [ABSTRACT FROM AUTHOR]

Background: With the conflict between the promise of ageing in health and longevity and the limited availability of health resources and social support, older adults in China inevitably experience anxieties surrounding health risks. This study aims to investigate how older adults perceive the health risks that come with getting older, explore the degree to which health risks affect older adults, and advocate for active engagement in practices for managing health risks. Methods: Using purposive sampling, three districts of Beijing (Xicheng District, Fengtai District, and Daxing District, respectively) were selected for the research. Qualitative semi-structured and in-depth interviews were conducted with 70 community-dwelling older adults who participated in the study. Data were extracted and analyzed based on a thematic framework approach. Results: Three main themes were identified: (i) the anxieties of older adults concerning health risks in ageing; (ii) the priorities of older adults for health risk management in ageing; (iii) the expectations of older adults for health risk management in ageing. The primary health concerns among older adults included disease incidence and function decline. It was found that basic health management emerged as a critical need for older adults to mitigate health risks. Moreover, it was observed that healthcare support for older adults from familial, institutional, and governmental levels exhibited varying degrees of inadequacy. Conclusions: The primary source of anxieties among older adults regarding health risks predominantly stems from a perceived sense of health deprivation. It is often compounded by persistent barriers to primary care of priorities in managing health risks among older adults. In addition, the expectations of older adults for health risk management emphasize the necessity for integrated care approaches. Therefore, further research should give priority to the prevention and management of health risks, aim to reduce anxieties, provide integrated care to meet the primary needs and expectations of older adults, and ultimately strive toward the overarching goal of promoting health and longevity. [ABSTRACT FROM AUTHOR]

Background: Candida auris is a new pathogen called "superbug fungus" which caused panic worldwide. There are no large-scale epidemiology studies by now, therefore a systematic review and meta-analysis was undertaken to determine the epidemic situation, drug resistance patterns and mortality of C. auris.Methods: We systematically searched studies on the clinical report of Candida auris in Pubmed, Embase and Cochrane databases until October 6, 2019. A standardized form was used for data collection, and then statics was performed with STATA11.0.Results: It showed that more than 4733 cases of C. auris were reported in over 33 countries, with more cases in South Africa, United States of America, India, Spain, United Kingdom, South Korea, Colombia and Pakistan. C. auirs exhibited a decrease in case count after 2016. Clade I and III were the most prevalent clades with more cases reported and wider geographical distribution. Blood stream infection was observed in 32% of the cases, which varied depending on the clades. Resistance to fluconazole, amphotericin B, caspofungin, micafungin and anidulafungin in C. auris were 91, 12, 12.1, 0.8 and 1.1%. The overall mortality of C. auris infection was 39%. Furthermore, subgroup analyses showed that mortality was higher in bloodstream infections (45%), and lower in Europe (20%).Conclusions: Over 4000 cases of C. auris were reported in at least 33 countries, which showed high resistance to fluconazole, moderate resistance to amphotericin B and caspofungin, high sensitivity to micafungin and anidulafungin. The crude mortality for BSI of C. auris was 45% which was similar to some drug-resistant bacteria previously reported. In conclusion, C. auris displayed similar characteristics to some drug resistance organisms. This study depicts several issues of C. auris that are most concerned, and is of great significance for the clinical management. [ABSTRACT FROM AUTHOR]

Background: The global prevalence of VCI has increased steadily in recent years, but diagnostic biomarkers for VCI in patients with non-disabling ischemic cerebrovascular incidents (NICE) remain indefinite. The primary objective of this research was to investigate the relationship between peripheral serological markers, white matter damage, and cognitive function in individuals with NICE. Methods: We collected clinical data, demographic information, and medical history from 257 patients with NICE. Using the MoCA upon admission, patients were categorized into either normal cognitive function (NCF) or VCI groups. Furthermore, they were classified as having mild white matter hyperintensity (mWMH) or severe WMH based on Fazekas scores. We then compared the levels of serological markers between the cognitive function groups and the WMH groups. Results: Among 257 patients with NICE, 165 were male and 92 were female. Lymphocyte count (OR = 0.448, P < 0.001) and LDL-C/HDL-C (OR = 0.725, P = 0.028) were protective factors for cognitive function in patients with NICE. The sWMH group had a higher age and inflammation markers but a lower MoCA score, and lymphocyte count than the mWMH group. In the mWMH group, lymphocyte count (AUC = 0.765, P < 0.001) and LDL-C/HDL-C (AUC = 0.740, P < 0.001) had an acceptable diagnostic value for the diagnosis of VCI. In the sWMH group, no significant differences were found in serological markers between the NCF and VCI groups. Conclusion: Lymphocyte count, LDL-C/HDL-C were independent protective factors for cognitive function in patients with NICE; they can be used as potential biological markers to distinguish VCI in patients with NICE and are applicable to subgroups of patients with mWMH. [ABSTRACT FROM AUTHOR]

Background: Mature fruit cracking during the normal season in African Pride (AP) atemoya is a major problem in postharvest storage. Our current understanding of the molecular mechanism underlying fruit cracking is limited. The aim of this study was to unravel the role starch degradation and cell wall polysaccharide metabolism in fruit ripening and cracking after harvest through transcriptome analysis. Results: Transcriptome analysis of AP atemoya pericarp from cracking fruits of ethylene treatments and controls was performed. KEGG pathway analysis revealed that the starch and sucrose metabolism pathway was significantly enriched, and approximately 39 DEGs could be functionally annotated, which included starch, cellulose, pectin, and other sugar metabolism-related genes. Starch, protopectin, and soluble pectin contents among the different cracking stages after ethylene treatment and the controls were monitored. The results revealed that ethylene accelerated starch degradation, inhibited protopectin synthesis, and enhanced the soluble pectin content, compared to the control, which coincides with the phenotype of ethylene-induced fruit cracking. Key genes implicated in the starch, pectin, and cellulose degradation were further investigated using RT-qPCR analysis. The results revealed that alpha-amylase 1 (AMY1), alpha-amylase 3 (AMY3), beta-amylase 1 (BAM1), beta-amylase 3 (BAM3), beta-amylase 9 (BAM9), pullulanase (PUL), and glycogen debranching enzyme (glgX), were the major genes involved in starch degradation. AMY1, BAM3, BAM9, PUL, and glgX all were upregulated and had higher expression levels with ethylene treatment compared to the controls, suggesting that ethylene treatment may be responsible for accelerating starch degradation. The expression profile of alpha-1,4-galacturonosyltransferase (GAUT) and granule-bound starch synthase (GBSS) coincided with protopectin content changes and could involve protopectin synthesis. Pectinesterase (PE), polygalacturonase (PG), and pectate lyase (PEL) all involved in pectin degradation; PE was significantly upregulated by ethylene and was the key enzyme implicated pectin degradation. Conclusion: Both KEGG pathway enrichment analysis of DEGs and material content analysis confirmed that starch decomposition into soluble sugars and cell wall polysaccharides metabolism are closely related to the ripening and cracking of AP atemoya. A link between gene up- or downregulation during different cracking stages of atemoya fruits and how their expression affects starch and pectin contents were established by RT-qPCR analysis. [ABSTRACT FROM AUTHOR]

Background: Hospital operation assistant (HOA) plays an important role in promoting the operation effectiveness and efficiency of hospital. China, as a resource-poor country, urgently needs to train HOA talent. The purpose of this study is to construct and validate a competency model for HOA, which can be used as a tool to select and train HOAs. Methods: Basic competency items were first constructed through literature review combined with the job analysis of HOA. Then, a questionnaire survey conducted on more than 300 hospital operation management-related staff was used to assess the importance of competency items. Exploratory factor analysis, structural equation model and second-order confirmatory factor analysis were used to construct and validate the competency model of HOA. Results: A total of 23 items were identified as critical to HOA capability, which were further divided into three factors: professional skills, professional knowledge and personality traits. The structural equation model showed that the standardized path coefficients of the three factors were 0.86, 0.82 and 0.98. The competency model passed strict fitting effect tests in several aspects, including root-mean-square error of approximation (RMSEA) = 0.077 (< 0.080), standardized root mean square residual (SRMR) = 0.062 (< 0.080), comparative fit index (CFI) = 0.927 (> 0.900) and Tucker-Lewis index (TLI) = 0.918 (> 0.900), which showed that the fitting validity of the model was ideal. The composite reliability (CR), average variance extracted (AVE) and correlation coefficients of all factors were within the standard range, which showed that the construction validity and discrimination validity of the model were ideal. Conclusion: Our study indicates that the competency model of HOA is an instrument with appropriate fit validity, construct validity and discriminant validity, which can provide criteria for selecting and training HOAs. [ABSTRACT FROM AUTHOR]

Background: Length of stay (LOS) is an important metric for evaluating the management of inpatients. This study aimed to explore the factors impacting the LOS of inpatients with type-2 diabetes mellitus (T2DM) and develop a predictive model for the early identification of inpatients with prolonged LOS. Methods: A 13-year multicenter retrospective study was conducted on 83,776 patients with T2DM to develop and validate a clinical predictive tool for prolonged LOS. Least absolute shrinkage and selection operator regression model and multivariable logistic regression analysis were adopted to build the risk model for prolonged LOS, and a nomogram was taken to visualize the model. Furthermore, receiver operating characteristic curves, calibration curves, and decision curve analysis and clinical impact curves were used to respectively validate the discrimination, calibration, and clinical applicability of the model. Results: The result showed that age, cerebral infarction, antihypertensive drug use, antiplatelet and anticoagulant use, past surgical history, past medical history, smoking, drinking, and neutrophil percentage-to-albumin ratio were closely related to the prolonged LOS. Area under the curve values of the nomogram in the training, internal validation, external validation set 1, and external validation set 2 were 0.803 (95% CI [confidence interval] 0.799–0.808), 0.794 (95% CI 0.788–0.800), 0.754 (95% CI 0.739–0.770), and 0.743 (95% CI 0.722–0.763), respectively. The calibration curves indicated that the nomogram had a strong calibration. Besides, decision curve analysis, and clinical impact curves exhibited that the nomogram had favorable clinical practical value. Besides, an online interface (https://cytjt007.shinyapps.io/prolonged%5flos/) was developed to provide convenient access for users. Conclusion: In sum, the proposed model could predict the possible prolonged LOS of inpatients with T2DM and help the clinicians to improve efficiency in bed management. [ABSTRACT FROM AUTHOR]

Background: Currently, population aging has been an obstacle and the spotlight for all countries. Compared with developed countries, problems caused by China's aging population are more prominent. Beijing, as a typical example, is characterized by advanced age and high disability rate, making this capital city scramble to take control of this severe problem. The main types of care for the disabled elderly are classified as home care, institutional care, and community care. With the obvious shortage of senior care institutions, most disabled elderly people are prone to choose home care. This kind of elderly care model is in line with the traditional Chinese concept and it can save the social cost of the disabled elderly to the greatest extent. However, home care for the disabled elderly is facing bumps from the whole society, such as lack of professional medical care, social support and humanistic care, and the care resources provided by a single subject cannot meet the needs of the disabled elderly. Objective: Based on the demands of the disabled elderly and their families, this study aims to explore the current status of home care service, look for what kind of care is more suitable for the disabled elderly, and try to find an appropriate elderly care mechanism which could meet the diverse needs of the disabled elderly. Methods: A total of 118 disabled elderly people and their primary caregivers were selected from four districts of Beijing by using multi-stage stratified proportional sampling method. A one-to-one and semi-structured in-depth qualitative interview were conducted in the study to find out the health status of the disabled elderly, the relationship between the disabled elderly and their primary caregivers, and utilization of elderly care resources, etc. The views of the interviewees were analyzed through the thematic framework method. All the methods were carried out in accordance with relevant guidelines and regulations. Results: The results showed that the average age of 118 disabled elderly is 81.38 ± 9.82 years; 86 (72.9%) are severe disability; 105 (89.0%)are plagued by chronic diseases; the average duration of disability is 5.63 ± 5.25 years; most of disabled elderly have 2 children, but the primary caregiver are their own partner (42, 35.6%), and there is an uneven sharing of responsibilities among the disabled elderly's offspring in the process of home care. The disabled elderly enjoy medical care services, rehabilitation training, daily health care, psychological and other demands. However, the disabled elderly and their families in Beijing face a significant financial burden, as well as physical and psychological issues. The care services provided by the government, family doctors, family members and social organizations fall far short of satisfying the diverse care needs of the disabled elderly. Conclusions: In order to effectively provide home care services for the disabled elderly, it is therefore necessary to establish a coordination mechanism of multiple subjects and give full play to the responsibilities of each subject. This study proposes a strengthening path for the common cooperation of multiple subjects, which taking specific responsibilities and participating in the home care for the disabled elderly: (1) The government should give full play to the top-level leading responsibilities and effectively implement people-oriented measures to the disabled elderly. (2) Family doctors strengthen their responsibilities as health gatekeepers and promote continuous health management of the disabled elderly. (3) Family members assume the main responsibility and provide a full range of basic care services. (4) Social forces promote supplementary responsibilities of public welfare and expand the connotation of personalized care services. (5) The disabled elderly should shoulder appropriate personal responsibility and actively cooperate with other subjects. [ABSTRACT FROM AUTHOR]

Background: In areas where Lyme disease is endemic, bites from ticks are common, but no vaccine is currently available against Lyme disease for humans. Therefore, the feasibility of using antibiotic prophylaxis to prevent Lyme disease after a tick bite is worth further exploration. Previous meta-analyses lack sufficient power to demonstrate the efficacy of about antibiotic prophylaxis for the prevention of Lyme disease following a tick bite. In this study, we explored more precise evidence and attempted to identify and update optimum treatment strategies.Methods: We searched PubMed, Embase, and the Cochrane Library for studies until March 23, 2021. We included studies if the enrolled patients were randomly allocated to a treatment or control group within 72 h following a tick bite and had no clinical evidence of Lyme disease at enrolment. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were followed for data abstraction. Two authors (GZZ and XX) independently reviewed the abstracts and identified articles for detailed assessment. We used a random-effects model to calculate the pooled results and reported the 95% confidence interval (CI). Study quality was assessed using a modified Jadad scale, and publication bias was assessed using Egger's test. We calculated the risk ratio (RR) for the rates of unfavorable events in patients who received intervention versus the control group. This study is registered with PROSPERO, number CRD42021245002.Results: Six studies (3,766 individuals) were included. The pooled rate of unfavorable events in persons receiving treatment and the control group were 0.4% (95%CI: 0.1-1.1%) and 2.2% (95%CI: 1.6-3.0%), respectively. The pooled RR was 0.38 (95%CI: 0.22-0.66). Subgroup analysis revealed that the pooled RR was 0.29 (95%CI: 0.14-0.60) in the single-use 200-mg doxycycline group; 0.28 (95%CI: 0.05-1.67) in a 10-day course group (Amoxicillin, Penicillin or tetracycline); and 0.73 (95%CI: 0.25-2.08) in a topical antibiotic treatment group (Azithromycin).Conclusions: The available evidence supports the use of antibiotics for the prevention of Lyme disease, and reveals advantages of using single-dose; however, further confirmation is needed. [ABSTRACT FROM AUTHOR]

Background: Poor endometrial receptivity is a major factor that leads to recurrent implantation failure. However, the traditional method cannot accurately evaluate endometrial receptivity. Various studies have indicated that microRNAs (miRNAs) are involved in multiple processes of embryo implantation, but the role of miRNAs in endometrial receptivity in patients with recurrent implantation failure (RIF) remains elusive. In the present study, we investigated the presence of pinopodes and the roles of miR-30d-5p, suppressor of cytokine signalling 1 (SOCS1) and the leukaemia inhibitory factor (LIF) pathway in women with a history of RIF during the implantation window. Methods: Endometrial tissue samples were collected between January 2018 to June 2019 from two groups of women who underwent in vitro fertilisation and embryo transfer (IVF-ET) or frozen ET. The RIF group included 20 women who underwent ≥ 3 ETs, including a total of ≥ 4 good-quality embryos, without pregnancy, whereas the control group included 10 women who had given birth at least once in the past year. An endometrial biopsy was performed during the implantation window (LH + 7). The development of pinopodes in the endometrial biopsy samples from all groups was evaluated using scanning electron microscopy (SEM). Quantitative reverse transcription-polymerase chain reaction and western blotting were used to investigate the expression levels of miR-30d-5p, SOCS1, and the LIF pathway. Results: The presence of developed pinopodes decreased in patients with RIF on LH + 7. The expression level of miR-30d-5p decreased in the endometria during the implantation window of patients with RIF, whereas the mRNA and protein levels of SOCS1 were significantly higher in the RIF group than in the control group. Furthermore, a negative correlation was observed between the expression of miR-30d-5p and SOCS1 (r2 = 0.8362). In addition, a significant decrease in LIF and p-STAT3 expression was observed during the implantation window in patients with RIF. Conclusions: MiR-30d-5p and SOCS1 may be potential biomarkers for endometrial receptivity. Changes in pinopode development and abnormal expression of miR-30d-5p, SOCS1 and LIF pathway in the endometrium could be the reasons for implantation failure. [ABSTRACT FROM AUTHOR]

Background: Fusarium wilt of banana is one of the most destructive diseases in banana-growing regions worldwide. Soil-borne diseases and soil microbial communities are closely related. The screening of antagonistic bacteria from soil microorganisms in areas with Fusarium wilt of banana is of great practical significance for controlling this disease. Results: A strain designated FS-4 was isolated from healthy banana rhizosphere soil in an area affected by Fusarium wilt. This strain exhibited a significant antagonistic effect on the pathogen. Pot experiments revealed that the fermentation broth of strain FS-4 not only decreased the incidence of banana Fusarium wilt, but also promoted the growth of banana seedlings. The strain was identified as Streptomyces ma. by its morphological, physiological, and biochemical characteristics and 16S rRNA gene sequence analysis. The culture and fermentation conditions for this strain were optimized by single-factor and response surface experiments. The optimum culture conditions for Streptomyces ma. FS-4 were as follows: peptone 0.5%, saccharose 2.4, 0.05% K2HPO4, 0.05% MgCl2, and 0.05% NaCl at an initial pH of 7.0; 180 g at 28 °C; and inoculation size of 6% for 62 h. The diameter of bacteriostasis circle for Bacillus subtilis reached 26.7 mm. Conclusion: Streptomyces ma. FS-4 is an important microbial resource as a biological agent for the control of plant pathogenic fungi and can be used to promote banana growth. [ABSTRACT FROM AUTHOR]

Background: JS-K is a nitric oxide (NO) donor and could generate intracellularly high levels of NO. The study explores PP2A as a tumor suppressor is a major determinant mediating JS-K-caused apoptosis in human hepatocellular carcinoma (HCC) cells. Methods: The human HCC cell lines (PLC5, Huh-7, Bel-7402, SMMC-7721 and HepG2) were used to assess effects of JS-K on cell viability, apoptosis induction and PP2A activation. Effects of JS-K on cell morphology, mitochondrial membrane potential, apoptosis and NO levels were determined in HCC cells expressing PP2A. Simultaneously, the expression of PP2A family including PP2A-A(α/β), PP2A-B55, PP2A-C(α/β) and the substrates of PP2A, such as β-catenin, c-Myc and p-Bcl-2 (Ser70) were detected in sensitive HCC cells. Furthermore, the role of NO in mediating the expression of PP2A was further validated with Z-VAD-FMK (a caspase inhibitor), Carboxy-PTIO (a NO scavenger), okadaic acid (OA, a PP2A inhibitor) and FTY720 (a PP2A agonist) in JS-K treated cells. In addition, the genetic manuplation of PP2A including overexpression and knockdown have been also performed in JS-K treated cells. Moreover, the rat model of primary hepatic carcinoma was established with diethylnitrosamine for 16 weeks to verify the anti-tumor effects of JS-K in vivo. Immunohistochemical and Western blot analysis were used to determine the expression of proteins in rat primary hepatic carcinoma tissues. Results: JS-K significantly inhibited cell proliferation, increased apoptosis rate and activated PP2A activity in five HCC cells viability, especially SMMC7721 and HepG2 cells. It was characterized by loss of mitochondrial membrane potential, significant externalization of phosphatidylserine, nuclear morphological changes. Moreover, JS-K enhanced Bax-to-Bcl-2 ratio, released cytochrome c (Cyt c) from mitochondria, activated cleaved-caspase-9/3 and the cleavage of PARP, and decreased the expression of X-linked inhibitor of apoptosis protein (XIAP). Both Z-VAD-FMK and Carboxy-PTIO suppressed the activation of cleaved-caspase-9/3 and of cleaved-PARP in JS-K-treated sensitive HCC cells. Simultaneously, JS-K treatment could lead to the activation of protein phosphatase 2A-C (PP2A-C) but not PP2A-A and PP2A-B55, which subsequently inactivated and dephosphorylated the PP2A substrates including β-catenin, c-Myc, and p-Bcl-2 (Ser70). However, silencing PP2A-C could abolish both the activation of PP2A-C and down-regulation of β-catenin, c-Myc and p-Bcl-2 (Ser70) in sensitive HCC cells. Conversely, PP2A overexpression could enhance the effects of JS-K on activation of PP2A and down-regulation of β-catenin, c-Myc and p-Bcl-2 (Ser70). In addition, adding okadaic acid (OA), a PP2A inhibitor, abolished the effects of JS-K on apoptosis induction, PP2A activation and the substrates of PP2A dephosphorylation; FTY720, a PP2A agonist, enhanced the effects of JS-K including apoptosis induction, PP2A activation and the substrates of PP2A dephosphorylation. The mice exhibited a lower number and smaller tumor nodules in response to JS-K-treated group. A marked increase in the number of hepatocytes with PCNA-positive nuclei (proliferating cells) was evident in DEN group and tended to decrease with JS-K treatment. Furthermore, JS-K treatment could induce PP2A activation and the substrates of PP2A inactivation such as β-catenin, c-Myc and p-Bcl-2(Ser70) in DEN-induced hepatocarcinogenesis. Conclusions: High levels of NO released from JS-K induces a caspase-dependent apoptosis through PP2A activation. [ABSTRACT FROM AUTHOR]

Objective: Self-rated health represents a reliable and important health measure related to general health and quality of life. This study aimed to identify the differences of health states of rural residents in a lower middle income setting in China and its associated factors. Methods: A descriptive study of a stratified random sample of 3870 individuals was conducted in rural Anhui during 2015. We investigated the influence of five independent variables: individual demographic characteristics, family factors, social capital traits, physical health conditions and healthy lifestyle habits of participants who self-related their health as good. A chi-square test and ordinal logistic regression analyses were used to identify the relationship of these variables and self-rated health. Results: The study found that respondents who negatively rated their health often were female, elderly, poor, lived alone, had low levels of education, inadequate social support, poor physical health, used healthcare services and lived in the lower economic regions. We found no significant correlations between self-rated health and employment, marital status, medical insurance, or exercise frequency. Surprisingly, smoking and drinking also seemed to be unrelated to poor self-reported health. Conclusion: Health differences based on region were apparent in rural China. We highlighted the possible impacts of income, age, physical health, education, advanced age, and social support on health. The results from this study could inform the delivery of appropriate health and social healthcare interventions to promote rural residents' health and quality of life. [ABSTRACT FROM AUTHOR]