CtIP suppresses primary microRNA maturation and promotes metastasis of colon cancer cells in a xenograft mouse model.

miRNAs are important regulators of eukaryotic gene expression. The post-transcriptional maturation of miRNAs is controlled by the Drosha-DiGeorge syndrome critical region gene 8 (DGCR8) microprocessor. Dysregulation of miRNA biogenesis has been implicated in the pathogenesis of human diseases, including cancers. C-terminal-binding protein-interacting protein (CtIP) is a well-known DNA repair factor that promotes the processing of DNA double-strand break (DSB) to initiate homologous recombination-mediated DSB repair. However, it was unclear whether CtIP has other unknown cellular functions. Here, we aimed to uncover the roles of CtIP in miRNA maturation and cancer cell metastasis. We found that CtIP is a potential regulatory factor that suppresses the processing of miRNA primary transcripts (pri-miRNA). CtIP directly bound to both DGCR8 and pri-miRNAs through a conserved Sae2-like domain, reduced the binding of Drosha to DGCR8 and pri-miRNA substrate, and inhibited processing activity of Drosha complex. CtIP depletion significantly increased the expression levels of a subset of mature miRNAs, including miR-302 family members that are associated with tumor progression and metastasis in several cancer types. We also found that CtIP-inhibited miRNAs, such as miR-302 family members, are not crucial for DSB repair. However, increase of miR-302b levels or loss of CtIP function severely suppressed human colon cancer cell line tumor cell metastasis in a mouse xenograft model. These studies reveal a previously unrecognized mechanism of CtIP in miRNA processing and tumor metastasis that represents a new function of CtIP in cancer.

Rapidly identifying bioactive compounds from Zhisou oral liquid by immobilized receptor-based high-performance affinity chromatography.

The identification of bioactive compounds in complex matrices remains a major challenge due to the lack of highly efficient and specific methods. This work developed an approach based on high-performance affinity chromatography to identify the potential antitussive compounds from Zhisou oral liquid . The main methods include the synthesis of immobilized beta2-adrenoceptor by a one-step method, the screening and identification of the potential bioactive compounds by the receptor column coupled with mass spectrometry, and the binding mechanism analysis of the compounds to the receptor by the in vivo experiment, injection amount dependent method and molecular simulation. We identified the potential bioactive compounds of Zhisou oral liquid as glycyrrhizic acid, platycodin D, tuberostemonine, and hesperidin. In vivo experiment showed that the combinational utilization of the four compounds was possible to present an equivalent antitussive effect to the formula. The docking results demonstrated that hydrogen bonds and Van der Waals forces were the main forces to drive the binding of the four compounds to beta2-adrenoceptor. We concluded that the four compounds are the effective components in Zhisou oral liquid. The proposed strategy is possible to provide an alternative for the development of highly efficient methods to pursue the bioactive compounds of complex matrices.

Measuring parent proxy-reported quality of life of 11 rare diseases in children in Zhejiang, China.

BACKGROUND: It has become increasingly important to measure the health-related quality of life (HRQoL) of rare diseases in children and adolescents in recent decades. Much attention has been paid to investigate the HROoL of a specific rare disease by self-report in previous studies. This study aimed to evaluate and compare the HROoL of 11 rare diseases in Chinese children by parent proxy-report, to explore the factors associated with HROoL of patients, and to understand the problems of most concern. METHODS: A total of 651 children aged from 2 to 18 were enrolled from the Children's Hospital Affiliated Zhejiang University in 2018. Their parents completed the parent proxy-report version of the Pediatric Quality of Life Inventory™ 4.0 (PedsQL™ 4.0). Independent samples t-test, one-way ANOVA, or Kruskal-Wallis H test was used to compare HROoL scores between groups. Multilevel linear regression models with random intercept were applied to analyze the relationship between socioeconomic variables and both the total score and subdomain scores. RESULTS: The total PedsQL scores of Patent ductus arteriosus (PDA), Infantile agranulocytosis, Autoimmune thrombocytopenia (ITP), Polysyndactyly, Hirschsprung disease, Cleft lip and palate, Tetralogy of fallot, Myasthenia gravis, Guillain-barre syndrome, Glycogen storage disease, and Langerhans cell histiocytosis children were 79.65 ± 5.46, 95.88 ± 3.48, 71.39 ± 3.27, 91.77 ± 6.35, 76.18 ± 6.92, 96.33 ± 4.22, 77.85 ± 8.90, 95.99 ± 3.31, 85.77 ± 4.56, 82.97 ± 4.13 and 77.6 ± 5.15, respectively. Age was significantly associated with physical functioning, school functioning, and psychosocial health scores. The household registration place was significantly related to the total score. The most urgent desire of patients was to reduce the overall medical costs. CONCLUSIONS: This study showed that patients with PDA had the lowest physical functioning score, while patients with ITP scored the lowest in the emotional functioning, social functioning, school functioning, psychosocial health, and total scores. Incentive policies should be further adopted to improve orphan drug availability and reduce the economic burden of rare diseases.

PLK1 targets CtIP to promote microhomology-mediated end joining.

Proper DNA double-strand break (DSB) repair is essential for maintaining genome integrity. Microhomology-mediated end joining (MMEJ) is an error-prone repair mechanism, which introduces mutations at break sites and contributes to chromosomal translocations and telomere fusions, thus driving carcinogenesis. Mitotic kinases PLK1, CDK1 and Aurora A are important for supporting MMEJ and are often overexpressed in various tumors. However, the functional interplay between these kinases and MMEJ has not been explored. Here, we found that MMEJ is preferentially employed to fix DSBs in cells arrested in mitosis following nocodazole treatment. We further showed that the DSB repair factor CtIP is jointly phosphorylated by CDK1/Aurora A and PLK1. CDK1/Aurora A-mediated CtIP phosphorylation at serine 327 triggers CtIP binding to the PLK1 polo-box domain, which in turn facilitates PLK1 to phosphorylate CtIP mainly at serine 723. A PLK1 phosphor-mimic CtIP mutant fails to initiate extended end resection and is thus unable to mediate homologous recombination and the G2/M checkpoint but can mediate MMEJ. These data imply that PLK1 may target CtIP to promote error-prone MMEJ and inactivate the G2/M checkpoint. These findings have helped elucidate the oncogenic roles of these factors.

Medical and socio-demographic characteristics associated with patient-perceived continuity of primary care: A cross-sectional survey in Hangzhou, China.

BACKGROUND: This study measured the perceived continuity of general practitioner (GP) care from the patient's perspective and identified the associated factors. METHODS: A cross-sectional survey was carried out on 624 patients in community health care centres in Hangzhou, China. A self-designed Likert scale was used to measure patients' perceptions on informational, managerial, and relational continuity of GP care. An average score for three types of continuity ranging from 0 to 100 was calculated. Linear regression models were developed to determine the factors influencing continuity. RESULTS: Average rating scores of 57.73 (±15.31), 50.74 (±17.18), 61.61 (±18.07), and 63.57 (±17.40) were found for total, informational, managerial, and relational continuity of care, respectively. Older patients reported a more positive rating on all types of continuity. Income was negatively associated with managerial continuity. The factors affecting informational, relational, and total continuities included chronic diseases, walking distance to nearest community health centres, signing a contract with a GP, and knowing the names of contracted GPs. CONCLUSION: Patients' perception of continuity of GP care remains at a low level, especially for informational continuity. The varied association between continuity of care and identified factors suggests that targeted actions should be considered for improving the quality of GP services.

Analytical performance of three diagnostic reagents for HBsAg on an automatic ELISA analyzer.

PURPOSE: We conducted performance tests of three HBsAg ELISA diagnostic reagents using an Addcare 600 (Yantai Addcare Bio-tech Limited Company) and studied the consistency between the qualitative results and chemiluminescent microparticle immunoassay (CMIA) results. METHODS: Diagnostic kits (ELISA) for HBsAg manufactured by INTEC ("A"), KHB ("B") and Wantai ("C") were tested on an Addcare 600 to evaluate their intermediate precision, repeatability, and C50. Furthermore, three ELISA detection systems and a quantitative test kit for HBsAg (Abbott) were employed to screen 1000 serum samples, while CMIA reactive samples were used to perform the confirmatory tests. The evaluation indexes of the ELISA reagent performances were calculated. RESULTS: The intermediate precision and repeatability of each system were <14% and <9%, respectively, while C50 was 0.105-0.115 IU/mL. The sensitivities of A, B, and C were 98.70%, 99.28%, and 99.13%, respectively, while their specificities were 98.06%, 99.03%, and 97.42%, respectively. The Youden indexes were 96.76%, 98.31%, and 96.55%, respectively, while the kappa values were 0.965 (P=.000), 0.981 (P=.000), and 0.967 (P=.000), respectively. CONCLUSION: The combination of Addcare 600 with the three reagents could meet the clinical requirement. Reagent B demonstrated the best performance. Although the results consistency among the three systems and CMIA was good, our findings suggest that ELISA should be combined with a confirmatory test to exclude false-positive and false-negative results caused by low HBsAg levels.

Inequality in the distribution of health resources and health services in China: hospitals versus primary care institutions.

BACKGROUND: Equity is one of the major goals of China's recent health system reform. This study aimed to evaluate the equality of the distribution of health resources and health services between hospitals and primary care institutions. METHODS: Data of this study were drawn from the China Health Statistical Year Books. We calculated Gini coefficients based on population size and geographic size, respectively, for the indicators: number of institutions, number of health workers and number of beds; and the concentration index (CI) for the indicators: per capita outpatient visits and annual hospitalization rates. RESULTS: The Gini coefficients against population size ranged between 0.17 and 0.44 in the hospital sector, indicating a relatively good equality. The primary care sector showed a slightly higher level of Gini coefficients (around 0.45) in the number of health workers. However, inequality was evident in the geographic distribution of health resources. The Gini coefficients exceeded 0.7 in the geographic distribution of institutions, health workers and beds in both the hospital and the primary care sectors, indicating high levels of inequality. The CI values of hospital inpatient care and outpatient visits to primary care institutions were small (ranging from -0.02 to 0.02), indicating good wealth-related equality. The CI values of outpatient visits to hospitals ranged from 0.16 to 0.21, indicating a concentration of services towards the richer populations. By contrast, the CI values of inpatient care in primary care institutions ranged from -0.24 to -0.22, indicating a concentration of services towards the poorer populations. The eastern developed region also had a high internal inequality compared with the other less developed regions. CONCLUSION: Significant inequality in the geographic distribution of health resources is evident, despite a more equitable per capita distribution of resources. Richer people are more likely to use well-resourced hospitals for outpatient care. By contrast, poorer people are more likely to use poorly-resourced primary care institutions for inpatient care. There is a risk of the emergence of a two-tiered health care delivery system.

Decomposing socioeconomic inequalities in depressive symptoms among the elderly in China.

BACKGROUND: Accelerated population ageing brings about unprecedented challenges to the health system in China. This study aimed to measure the prevalence and the income-related inequality of depressive symptoms, and also identify the determinants of depressive symptom inequality among the elderly in China. METHODS: Data were drawn from the second wave of the China Health and Retirement Longitudinal Study (CHARLS). Depressive symptoms were assessed with a 10-item Center for Epidemiologic Studies-Depression Scale (CES-D), which was preselected in CHARLS. The concentration index was used to measure the magnitude of income-related inequality in depressive symptoms. A decomposition analysis, based on the logit model, was employed to quantify the contribution of each determinant to total inequality. RESULTS: More than 32.55% of the elderly in China had depressive symptoms. Women had a higher prevalence of depressive symptoms than men. The overall concentration index of depressive symptoms was -0.0645 among the elderly, indicating that depressive symptoms are more concentrated among the elderly who lived in economically disadvantaged situations, favoring the rich. Income was found to have the largest percentage of contribution to overall inequality, followed by residents' location and educational attainment. CONCLUSION: The prevalence of depressive symptoms in the elderly was considerably high in China. There was also a pro-rich inequality in depressive symptoms amongst elderly Chinese. It is suggested that some form of policy and intervention strategies, such as establishing the urban-rural integrated medical insurance scheme, enhancing the medical assistance system, and promoting health education programs, is required to alleviate inequitable distribution of depressive symptoms.

Use of appropriate healthcare technologies: a cross-sectional study in rural Zhejiang of China.

BACKGROUND: Appropriate healthcare technologies (AHTs) are an important strategy for improving the availability and accessibility of healthcare services. It is not clear what impact AHTs have on health workers and consumers; and whether those AHTs can continue in place without special or ongoing financial support. This study investigated the attitudes of health workers and consumers towards AHTs. METHODS: Health facilities from five counties in Zhejiang were surveyed. Participants of the study included all health workers who were involved in the delivery of AHTs in the selected organizations and a group of randomly selected patients who sought services from the participating organizations. A total of 822 questionnaires from health workers and 693 questionnaires from patients were collected for data analyses. The questionnaires measured perceptions and attitudes of respondents towards AHTs using a Likert scale. RESULTS: The respondents delivering public health services rated the highest scores to AHTs (4.42 ± 0.7), followed by those engaged in management of chronic conditions (4.41 ± 0.57) and Traditional Chinese Medicine (TCM) (4.29 ± 0.55). Around 90% of health workers believed that AHTs were meaningful for rural patients; however, only 69% of health workers believed that the technologies encouraged by the government were sufficiently developed or "mature", and more than 24% acknowledged difficulties in using those technologies. Overall, patients were satisfied with AHTs, with 71.6% feeling "very satisfied" or "satisfied", 24.2% feeling "acceptable" and 1.6% feeling "dissatisfied". Most (83%) patients were satisfied or very satisfied with Traditional Chinese Medicine, compared with management of chronic conditions (80%), family planning (67%), public health services (64%), and finally with maternal and child health care (59%). CONCLUSIONS: Local acceptability should be taken into consideration in determination of AHTs; consumer health literacy needs improvement, particularly in relation to public health and preventive services.

Utility of Goal Attainment Scaling (GAS) in evaluating a multicomponent exercise programme for community-dwelling pre-frail older adults.

OBJECTIVES: This study aimed to investigate the effectiveness of Goal Attainment Scaling (GAS) in assessing an intervention for pre-frail senior citizens. Additionally, the study aimed to explain how the GAS goals were established based on the International Classification of Functioning, Disability and Health (ICF) categories, including body function, activity and participation and environmental factors. METHODS: In this study, 220 pre-frail older adults were randomly selected to participate in a controlled trial. The intervention group engaged in multicomponent exercise three times a week, once at a community health service location and twice at home. The control group received advice on physical activity but did not have supervised exercise. Participants in both groups selected individualised GAS goals from 23 goals developed based on ICF by focus group discussion. The study used generalised estimating equations to analyse the differences between the groups. RESULTS: The study included 144 participants, 72 in the exercise group and 72 in the control group. The top three individualised goals for all participants were vestibular functions (53.5%), pain management (43.1%) and lifting and carrying objects (31.9%). Both groups saw a significant increase in GAS scores at week 8 and week 24 of the intervention (p<0.05), but the exercise group showed a more significant improvement (p<0.05). The participants living alone were associated with lower postintervention improvements in the GAS scores. In contrast, the participants who were using a smartphone were likely to get higher postintervention improvements in the GAS scores. CONCLUSIONS: GAS can be a valuable tool for setting and evaluating individualised and meaningful goals in body functions, activity and participation and environmental factors. The multicomponent exercise interventions can help pre-frail older adults achieve their expected goals as measured by the GAS.

Cyclin-dependent kinase 5 negatively regulates antiviral immune response by disrupting myeloid differentiation primary response protein 88 self-association.

As a member of the pattern recognition receptors (PRRs) involving in the innate immune system, Toll-like receptors (TLRs) can sense a wide range of microbial pathogens and combat infections by producing antimicrobial products, inflammatory cytokines, and chemokines. All TLRs, with the exception of TLR3, activate a signalling cascade via the myeloid differentiation primary response gene 88 (MyD88). Therefore, the activation of MyD88-dependent signalling pathway must be finely controlled. Herein, we identified that cyclin-dependent kinase 5 (CDK5) negatively regulated TLR-MyD88 signalling pathway by targeting MyD88. Overexpression of CDK5 reduced the production of interferons (IFNs), while a deficiency in CDK5 increased the expression of IFNs in response to vesicular stomatitis virus (VSV) infection. Mechanistically, CDK5 suppressed the formation of MyD88 homodimers, resulting in the attenuated production of IFNs induced by VSV infection. Surprisingly, its kinase activity does not play a role in this process. Therefore, CDK5 can act as an internal regulator to prevent excessive production of IFNs by restricting TLR-MyD88-induced activation of antiviral innate immunity in A549 cells.

Perceived Quality of Traditional Chinese Medicine Care in Community Health Services: A Cross-Sectional Survey in Hangzhou of China.

Background: Traditional Chinese medicine (TCM) is an integral part of the mainstream health care system in China. Public community health services are required by the government to deliver TCM services. This study aimed to assess patient perceived quality of TCM care in community health services. Methods: A cross-sectional questionnaire survey was conducted on 471 TCM users in four community health centers in Hangzhou. Respondents were asked to rate their experiences on a Likert scale about tangibility, reliability, responsiveness, assurance and empathy of the TCM services they received. Linear regression models were established to determine the sociodemographic and services factors associated with the ratings. Results: Average ratings on the five aspects of the TCM care ranged from 78 to 88 out of a possible 100, with assurance attracting the highest and empathy attracting the lowest score. Overall, higher perceived quality of TCM care (except for assurance) was associated with a choice of TCM in preference to western medicine. Those who reported higher cost (≥100 yuan) of TCM care rated higher on responsiveness and empathy of the care. But higher frequency of visits to community TCM services was associated with lower ratings on reliability, assurance and empathy. Those who received two or more TCM modalities also perceived lower tangible care. In addition, higher ratings on reliability and responsiveness were found in women. The respondents with a university qualification gave higher ratings on reliability and responsiveness; by contrast, those with a highest education of senior high school rated lower on assurance and empathy. Lower perceived tangibility and assurance was also associated with rural residency. Compared with those working in the public sector, the respondents from the retail and services sector gave a higher rating on assurance but a lower rating on empathy. Conclusion: Overall, the TCM users perceived high quality of TCM care in community health services in Hangzhou. However, there is a need to further improve TCM care from all quality perspectives in order to attract and maintain consumer trust in TCM.

Policy Goals of Contract Arrangements in Primary Care in Jeopardy: A Cross-Sectional Consumer Satisfaction Survey of Community Residents in Hangzhou, China.

Objective: China is attempting to establish a voluntary contracting system in primary care. This study aimed to determine the degree of consumer satisfaction with the entitlements of contract arrangements and its associated factors. Methods: A stratified cluster sampling strategy was adopted to recruit study participants from three administrative districts of Hangzhou municipality, each containing six residential communities. In each community, 50 households were recruited. A questionnaire was administered through face-to-face interviews with members of the households who signed a contract with community health centers, to collect data regarding their sociodemographic characteristics, health conditions, and knowledge of and attitudes toward the contract entitlements. Consumer satisfaction was measured using six items rated on a five-point Likert scale ranging from "1=very dissatisfied" to "5=very satisfied" and a summed score was calculated. A mixed linear regression model was established to identify individual predictors of consumer satisfaction after adjustment of the random (intercept) effect of household clusters. Results: Overall, the respondents reported low levels of awareness and understanding of the contract entitlements, with an average knowledge score of 8.21 (SD = 3.74) out of a maximum possible of 19. The respondents had relatively lower levels of satisfaction (satisfied or very satisfied) with their prioritized entitlements (51.5%) and hospitals at home and telemedicine services (31.3%), compared with the contract and insurance policies (85.5%) and medical services provided (87.0%). Female gender, older age, chronic conditions, and perceived better health were associated with higher levels of satisfaction, while poor awareness and knowledge were associated with lower levels of satisfaction. Conclusion: The study participants perceived limited benefits from the contract arrangements in primary care, which may jeopardize the policy purpose of the arrangements to encourage patients to use primary care as the first contact point in accessing health care services. It is evident that consumer satisfaction with the contract entitlements varies by healthcare needs. Lower levels of satisfaction are associated with poor awareness and knowledge of the entitlements.

Effect of Gas Counter Pressure on the Surface Roughness, Morphology, and Tensile Strength between Microcellular and Conventional Injection-Molded PP Parts.

Microcellular injection-molded parts have surface defect problems. Gas counter pressure (GCP) is one of the methods to reduce surface defects. This study investigated the effect of GCP on the surface roughness, morphology, and tensile strength of foamed and conventional injection-molded polypropylene (PP) products. GCP is generated by filling up the mold cavity with nitrogen during the injection-molding (IM) process. It can delay foaming and affect flow characteristics of microcellular and conventional injection-molding, which cause changes in the tensile strength, flow length, cell morphology, and surface quality of molded parts. The mechanism was investigated through a series of experiments including tuning of GCP and pressure holding duration. Surface roughness of the molded parts decreased with the increase in GCP and pressure holding duration. Compared to microcellular IM, GCP-assisted foaming exhibited much better surface quality and controllable skin layer thickness.

Electronic cigarette knowledge, attitudes and use among students at a university in Hangzhou, China.

INTRODUCTION: Electronic cigarettes are increasingly popular worldwide, especially among youth. There is growing evidence of the negative health consequences of vaping. Our objective was to assess university students' knowledge and attitudes regarding electronic cigarettes (e-cigarettes), their use, as well as the associated influencing factors for their use. METHODS: The study involved an online cross-sectional survey conducted between November 2019 and March 2020 in a university in Hangzhou, China. A total of 563 students completed the questionnaire. Descriptive statistics were used to assess characteristics, knowledge, and attitudes; t-tests, χ2-tests and logistic regression models were used to identify factors associated with ever e-cigarette use. RESULTS: In all, 59.9% of respondents were female and the average age was 20.38 years (SD=1.32). Only 42.6% of the respondents thought that e-cigarettes contain nicotine, 31.1% thought e-cigarettes are tobacco products, and 8.2% of the students reported being ever e-cigarettes users. In regard to attitude, the average score of the students in the Safety dimension was 3.34 (SD=0.64), followed by the Restriction dimension (Mean=2.66, SD=0.83). Correlates of ever use included regions, friends' and roommates' ever e-cigarette use, and higher attitude score in the Supervision dimension. CONCLUSIONS: The university students' level of knowledge regarding e-cigarettes was not high, and their attitudes regarding e-cigarettes were not that supportive. Students' ever use of e-cigarettes at a university in Hangzhou was higher than for university students in other cities in China, but lower than for those in foreign countries.

Perceived Social Support and Associated Factors Among Community-Dwelling Older Adults With Frailty and Pre-frailty in Hangzhou, China.

Objectives: The present study aimed to explore the social support among community-dwelling older adults with frailty and pre-frailty and to ascertain associated factors. Methods: The frailty status of the participant was assessed via the Chinese FRAIL Scale. The dependent variable, level of social support, was evaluated using the Social Support Rating Scale (range: 12-66). This study explored the influencing factors from three aspects containing sociodemographic characteristics, family environment, and community environment. Independent-sample t-test, Analysis of Variance, and multiple linear regression analyses were conducted to examine determinants of social support. Results: There were significant differences in overall social support between non-frail, pre-frail, and frail participants [38.01 (SD = 6.48) vs. 33.62 (SD = 6.25) vs. 30.50 (SD = 6.68), F = 62.157, p < 0.001]. Older adults with frailty and pre-frailty who were single would have lower levels of overall social support. In the pre-frail group, living alone was associated with lower overall social support. In contrast, the relationship with children and the availability of recreational activities were associated factors for the frail group. Conclusions: The level of social support among frail and pre-frail community-dwelling older adults was lower than the robust older adults and influenced by different factors according to the frailty category, which suggests taking targeted measures for social support improvement.

Lean non-alcoholic fatty liver disease (Lean-NAFLD) and the development of metabolic syndrome: a retrospective study.

Lean NAFLD is a special phenotypic closely correlated with metabolic syndrome (MS). The aim of this study is to investigate the MS development and the gender differences in lean NAFLD population. Participants were divided into 4 groups by BMI and NAFLD status. Descriptive analysis was performed to characterize baseline information. A total of 18,395 subjects were participated, and 1524 incident cases of MS were documented. Then, Kaplan-Meier curves were used to present the MS outcomes in different groups, and the NAFLD was found to be a riskier factor than obesity for MS. Subgroup analysis showed significantly higher MS incidence in female than male among lean NAFLD group, which is different from other groups. Although with higher prevalence in male, lean NAFLD seems to be a more harmful phenotype for females according to the TG, ALT and GGT levels. The logistic regressive analysis was performed to show the impact of NAFLD status and BMI changes on MS risk. Lean non-NAFLD subjects merely developed to NAFLD with no BMI status changes exhibited highest MS risk (ORs = 1.879, 95% CI 1.610-2.292) than that with both BMI increase and NAFLD development (ORs = 1.669, 95% CI 1.325-2.104). It also suggests the metabolic specificity of this population.

[Preventive and therapeutic effects of Chinese herbal medicine Compound Zhuye Shigao Granule in rats with radiation-induced esophagitis].

OBJECTIVE: To explore the preventive and therapeutic effects of Compound Zhuye Shigao Granule (CZSG), a compound Chinese herbal medicine, on radiation-induced esophagitis in rats. METHODS: Fifty-six Wistar rats were randomly divided into 5 groups: normal control group (8 rats), model group (12 rats), and high-, medium- and low-dose CZSG groups (12 rats in each group). The rats in the normal control and model groups were given normal saline 10 mL/kg body weight and those in the CZSG-treated groups were given solution of CZSG at doses of 1.15, 2.30, or 4.60 g/kg body weight respectively by intragastric administration once a day for 7 days. Then esophagitis was induced by local irradiation of (60)Co ray (490.25 cGy/min, totaled 30 Gy). The administration was continued for another 7 days or 14 days, meanwhile body weight and daily food intake of the rats were recorded. Seven days after the irradiation, 4 rats in each group were sacrificed under anesthesia, then, the esophageal tissue was obtained for histopathological examination and the degrees of esophageal tissue injury and neutrophil infiltration were scored. Fourteen days after the irradiation, all the survival rats were dealt in the same way. RESULTS: (1) Seven days after the irradiation, the esophageal tissue sections in the model group showed typical histopathological changes of radiation-induced esophagitis, whereas in the CZSG groups the histopathological changes were lessened dose-dependently and in the high-dose CZSG group the esophageal tissue remained basically intact. (2) The scores of esophageal tissue injury and cellular infiltration in the high- and medium-dose CZSG groups were both significantly less than in the model group (P<0.05). (3) The body weight of the rats increased in the normal control group, whereas it decreased obviously in the model group. In the medium- and high-dose CZSG groups, it did not decrease significantly. The decrease of body weight in the high-dose CZSG group was less than that in the model group (P<0.05). (4) Compared with the normal control group, the daily food intake was reduced in the other groups. However, it was significantly greater in the low, medium- and high-dose CZSG groups than in the model group (P<0.05). CONCLUSION: In rats with radiation-induced esophagitis, CZSG can effectively relieve the esophageal tissue injury and cellular infiltration, increase daily food intake, and prevent rats from lose of body weight dose-dependently, which show that CZSG has the preventive and therapeutic effects for radiation-induced esophagitis in rats.

Development and characterization of a selective chromatographic approach to the rapid discovery of ligands binding to muscarinic-3 acetylcholine receptor.

The pursuit of new ligands binding to muscarinic-3 acetylcholine receptor (M3R) is viewed as challenging due to the lack of screening methods with high efficiency. To address such challenges, this work developed and characterized an approach to the rapid discovery of M3R ligands using the immobilized receptor as the chromatographic stationary phase. We fused haloalkane dehalogenase (Halo) as a tag at the C-terminus of M3R. The fusion M3R was immobilized on 6-chlorocaproic acid-activated ammino-microspheres by the specific covalent reaction between the Halo-tag and the linker. Comprehensive characterizations of the immobilized M3R were performed by scanning electron microscope, X-ray photoelectron spectroscopy, and the investigation on the binding of three specific ligands to the receptor. The feasibility of the immobilized M3R in complex matrices was tested by screening the bioactive compounds in Zhisou oral liquid, assessing the interaction between the screened compounds and the receptor using zonal elution, and evaluating the in vivo activity of the targeted compounds. The results evidenced that the immobilized M3R has high specificity, good stability, and the capacity to separate M3R ligands from complex matrices. These allowed us to identify naringin, hesperidin, liquiritigenin, platycodin D, and glycyrrhizic acid as the potential ligands of M3R. The association constants of the five compounds to M3R were 4.44 × 104, 1.11 × 104, 7.20 × 104, 4.15 × 104, and 3.36 × 104 M-1. The synergistic application of the five compounds exhibited an equivalent expectorant activity to the original formula. We reasoned that the current method is possible to provide a highly efficient strategy for the discovery of receptor ligands.

Evaluating Traditional Chinese Medicine Interventions on Chronic Low Back Pain Using Goal Attainment Scaling.

BACKGROUND: Extensive studies have been conducted to evaluate the pain relief effect of traditional Chinese medicine (TCM) interventions on patients with low back pain, including in China. However, there is a dearth in the literature documenting the diverse goals of TCM interventions, let alone the overall effect of such interventions. In this study, the goal attainment scaling (GAS) method was adopted to evaluate individualised TCM interventions on chronic low back pain. METHODS: A pre-post intervention study was conducted on patients with chronic low back pain who received individualised TCM interventions in community health services. The study was undertaken in three community health centres in Hangzhou of China. A total of 165 eligible patients were invited, and 150 participated in the study, including 136 who completed both pre- and postintervention surveys. Each participant was asked to identify three to five intended goals from a pool of 26 outcome indicators and their corresponding expectations of these goals prior to the TCM interventions. Their conditions were rated against the selected indicators on a self-report five-point Likert scale before and after the TCM interventions, respectively. Gaps between the actual conditions and the expected goals were summed up for each participant and converted into a standardised GAS score, with a higher score indicating higher achievements, and 50 indicting patient expectations were met. Linear regression models were established to determine the factors associated with the pre-post GAS changes after adjustment for variations in other variables. RESULTS: On average, an increase of 14.99 (SD = 9.81) in the GAS scores was achieved. This resulted in a mean GAS score of 48.33 (SD = 9.74) after the TCM interventions, falling slightly short (<2) of patient expectations. The multivariate linear regression models revealed that local residents, the retired, and those who perceived lower professional competency of their attending doctors had a smaller increase in the GAS scores after adjustment for variations in other variables. CONCLUSION: The individualised TCM interventions can help patients with low back pain to achieve their expected goals as measured by the GAS. Further studies are needed to better understand how patients set up their goals and the professional competency requirements to meet patient expectations.