Meroterpenoids from Marine Sponge Hyrtios sp. and Their Anticancer Activity against Human Colorectal Cancer Cells.

Two new meroterpenoids, hyrtamide A (1) and hyrfarnediol A (2), along with two known ones, 3-farnesyl-4-hydroxybenzoic acid methyl ester (3) and dictyoceratin C (4), were isolated from a South China Sea sponge Hyrtios sp. Their structures were elucidated by NMR and MS data. Compounds 2-4 exhibited weak cytotoxicity against human colorectal cancer cells (HCT-116), showing IC50 values of 41.6, 45.0, and 37.3 µM, respectively. Furthermore, compounds 3 and 4 significantly suppressed the invasion of HCT-116 cells while also downregulating the expression of vascular endothelial growth factor receptor 1 (VEGFR-1) and vimentin proteins, which are key markers associated with angiogenesis and epithelial-mesenchymal transition (EMT). Our findings suggest that compounds 3 and 4 may exert their anti-invasive effects on tumor cells by inhibiting the expression of VEGFR-1 and impeding the process of EMT.

Isolation and absolute configuration of alkylpyridine alkaloids from the marine sponge Hippospongia lachne.

Marine sponges are well known as prolific producers of structurally diverse molecules with valuable pharmacological potential. As part of our ongoing program to discover bioactive compounds from marine sponges collected from the Xisha Islands in the South China Sea, a chemical study on the specimens of Hippospongia lachne was conducted. As a result, eight undescribed compounds, including four zwitterionic alkylpyridinium salts, hippospondines A-D (1-4), and four 3-alkylpyridine alkaloids, hippospondines E (5), F (6), and (±)-hippospondine G (7), were isolated from the marine sponge H. lachne, together with one known 3-alkylpyridine alkaloid (8). The undescribed structures were elucidated by HRESIMS, NMR, DP4+ and CP3 probability analysis, and the Snatzke's method. Hippospondines A-D (1-4) represent the rare example of inner salt type alkylpyridinium alkaloid with a farnesyl moiety. Compounds 1-3 and 8 were subjected to cytotoxic and lymphocyte proliferation assays. Compound 3 exhibited a weak promotion effect on the ConA-induced T lymphocyte proliferation.

Effects of different doses of long-acting growth hormone in treating children with growth hormone deficiency.

BACKGROUND: With the improvement of economy and living standards, the attention paid to short stature in children has been increasingly highlighted. Numerous causes can lead to short stature in children, among which growth hormone deficiency (GHD) is a significant factor. AIM: To investigate the long-term efficacy and safety of different doses of long-acting polyethylene glycol recombinant human growth hormone (PEG-rhGH) in the treatment of GHD in children. METHODS: We selected 44 pediatric patients diagnosed with GHD who were treated at Wuhu First People's Hospital from 2014 to 2018. Total 23 patients were administered a high dose of long-acting PEG-rhGH at 0.2 mg/kg subcutaneously each week, forming the high-dose group. Meanwhile, 21 patients were given a lower dose of long-acting PEG-rhGH at 0.14 mg/kg subcutaneously each week, establishing the low-dose Group. The total treatment period was 2 years, during which we monitored the patients' height, annual growth velocity (GV), height standard deviation score (HtSDS), chronological age (CA), bone age (BA), and serum levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) before treatment and at 6 mo, 1 year, and 2 years after treatment initiation. We also monitored thyroid function, fasting plasma glucose, fasting insulin, and other side effects. Furthermore, we calculated the homeostatic model assessment for insulin resistance. RESULTS: After 1 year of treatment, the GV, HtSDS, IGF-1, BA, and IGFBP-3 in both groups significantly improved compared to the pre-treatment levels (P < 0.05). Moreover, when comparing GV, HtSDS, IGF-1, BA, and IGFBP-3 between the two groups, there were no statistically significant differences either before or after the treatment (P > 0.05). During the treatment intervals of 0-1.0 years and 1.0-2.0 years, both patient groups experienced a slowdown in GV and a decline in HtSDS improvement (P < 0.05). CONCLUSION: The use of PEG-rhGH in treating GHD patients was confirmed to be effective, with similar outcomes observed in both the high-dose group and low-dose groups, and no significant differences in the main side effects.

Internet-Based Cognitive Behavioral Therapy and Virtual Reality Exposure Therapy for Social Anxiety Disorder: Protocol for a Randomized Controlled Trial in Hong Kong.

BACKGROUND: Social anxiety disorder (SAD), also known as social phobia, is one of the most common mental disorders worldwide. In Hong Kong, the prevalence of SAD is high, but its treatment rate is low. SAD has immense impact on academic or work performance, social life, career development, and quality of life. One of the most effective treatments for SAD is cognitive behavioral therapy (CBT), with internet-based CBT (iCBT) and virtual reality exposure therapy (VRET) showing promise in treating SAD. However, internet interventions are underdeveloped in Chinese communities including Hong Kong. OBJECTIVE: This study aims to develop an iCBT program that includes VRET, called "Ease Anxiety in Social Event Online" (Ease Online), for Hong Kong adults with SAD in a randomized controlled trial. METHODS: The 14-week Ease Online program is a guided self-help iCBT program with a blended mode of service delivery. The program comprises 9 web-based modules and 5 individual counseling sessions (including 2 VRET sessions) conducted remotely or face-to-face with a therapist to provide therapist support, as guided iCBT shows superior effects than unguided iCBT. Other program components include therapist feedback on assignments, internal messages, forums, client portfolios, web-based questionnaires, reminders, and web-based bookings. The program can be accessed either through a mobile app or program website through a PC with an internet connection. The participants are openly recruited and screened using a questionnaire and through an intake interview. Eligible participants are randomized by placing them into a web-based iCBT group, app-based iCBT group, or a waitlist control (WLC) group. Participants in the WLC group are assigned to the app-based program upon completion of the service of the 2 experimental groups. Measurements of social anxiety, depression and anxiety symptoms, psychological distress, automatic thoughts, and quality of life are administered at pretest, posttest, and 3- and 6-month follow-ups. Multivariate ANOVA with repeated measures will be performed to determine the intervention effectiveness on the continuous variables over time. RESULTS: Participant recruitment commenced in January 2021. As of February 2023, a total of 1811 individuals applied for the Ease Online program. In total, 401 intake interviews have been completed, and 329 eligible participants have joined the program, among whom 166 have completed the service. Data collection is still ongoing, which is expected to be completed in March 2024. CONCLUSIONS: This study is the first of its kind in combining iCBT and VRET for the treatment of SAD in Hong Kong. At a theoretical level, this study contributes to the development and evaluation of internet-based psychological interventions in Hong Kong. At a practical level, the Ease Online program may serve as an alternative service option for SAD clients in Hong Kong if proven effective. TRIAL REGISTRATION: ClinicalTrials.gov NCT04995913; https://clinicaltrials.gov/study/NCT04995913. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/48437.

A therapist-guided internet-based cognitive behavioral therapy program for Hong Kong university students with psychological distress: A study protocol for a randomized controlled trial.

Background: University students are at high risk of various mental health problems due to high levels of psychological distress. However, university counseling services are often inadequate to meet their mental health needs due to shortage of mental health professionals, especially in Hong Kong. Internet-based cognitive behavioral therapy (iCBT) has shown similar effects as those of face-to-face CBT in addressing these mental health concerns, but few iCBT programs have been developed for Hong Kong university students. Objective: This study protocol aims to develop and evaluate a culturally and linguistically appropriate iCBT program called "REST Online" to reduce the psychological distress and improve the mental health of Chinese university students in Hong Kong in a randomized controlled trial (RCT). Method: The contents and functionality of the "REST Online" program which includes both web- and app-based versions, are described. A blended mode of service delivery is adopted, with 8 online modules and 2 counseling sessions. Therapist support will be provided by a CBT therapist. A total of 338 Chinese university students with mild to moderate levels of psychological distress will be openly recruited and randomized to three groups: the (1) web-based and (2) app-based "REST Online" groups, and (3) waitlist control group. The program effectiveness is evaluated in psychological distress, depression and anxiety symptoms, and positive and negative emotions and positive and negative thoughts at pre-, post- and 3-month follow-up tests. Linear mixed effect models will be conducted for data analysis. Discussion: The "REST Online" program is among the first of its kind to address the mental health needs of Hong Kong university students by an internet intervention. Theoretically, this study will provide some empirical evidence for the effectiveness of this iCBT program in the Hong Kong context for Chinese clients. Practically, if proven effective, this program can be provided to local university counselors as an option for service delivery. Strengths and limitations are also discussed.

Long-term Pegylated GH for Children With GH Deficiency: A Large, Prospective, Real-world Study.

CONTEXT: The evidence of long-term polyethylene glycol recombinant human GH (PEG-rhGH) in pediatric GH deficiency (GHD) is limited. OBJECTIVE: This study aimed to examine the effectiveness and safety of long-term PEG-rhGH in children with GHD in the real world, as well as to examine the effects of dose on patient outcomes. DESIGN: A prospective, observational, posttrial study (NCT03290235). SETTING, PARTICIPANTS AND INTERVENTION: Children with GHD were enrolled from 81 centers in China in 4 individual clinical trials and received weekly 0.2 mg/kg/wk (high-dose) or 0.1 to <0.2 mg/kg/wk (low-dose) PEG-rhGH for 30 months. MAIN OUTCOMES MEASURES: Height SD score (Ht SDS) at 12, 24, and 36 months. RESULTS: A total of 1170 children were enrolled in this posttrial study, with 642 patients in the high-dose subgroup and 528 in the low-dose subgroup. The Ht SDS improved significantly after treatment in the total population (P < 0.0001), with a mean change of 0.53 ± 0.30, 0.89 ± 0.48, 1.35 ± 0.63, 1.63 ± 0.75 at 6 months, 12 months, 24 months, and 36 months, respectively. In addition, the changes in Ht SDS from baseline were significantly improved in the high-dose subgroup compared with the low-dose subgroup at 6, 12, 24, and 36 months after treatment (all P < 0.05). A total of 12 (1.03%) patients developed serious adverse events. There was no serious adverse event related to the treatment, and no AEs leading to treatment discontinuation or death occurred. CONCLUSIONS: PEG-rhGH showed long-term effectiveness and safety in treating children with GHD. Both dose subgroups showed promising outcomes, whereas PEG-rhGH 0.2 mg/kg/wk might show additional benefit.

Short-term efficacy and safety of a lower dose of polyethylene glycol recombinant human growth hormone in children with growth hormone deficiency: A randomized, dose-comparison study.

Objective: Polyethylene glycol recombinant human growth hormone (PEG-rhGH, Jintrolong®) is the first long-acting rhGH preparation that is approved to treat children with growth hormone deficiency (GHD) in China. Clinical experience with dose selections of PEG-rhGH is scarce. The present study compared the efficacy and safety of a lower dose to increase dosing regimens of PEG-rhGH treatment. Methods: A multicenter, randomized, open-label, dose-comparison clinical study was conducted to compare the improvements in the height standard deviation score (Ht SDS), height velocity (HV), insulin-like growth factor-1 (IGF-1) SDS, and safety profiles of children with GHD who are treated with 0.2 mg/kg/week of PEG-rhGH dose or 0.14 mg/kg/week for 26 weeks. Results: Ht SDS, HV, and IGF-1 SDS increased significantly after PEG-rhGH treatment in the two dose groups (p < 0.05). The improvements of Ht SDS, HV, and IGF-1 SDS were more significant in the high-dose group than in the low-dose group (p < 0.05). Ht SDS improvement in low-dose group was not non-inferiority to that in the high-dose group (p = 0.2987). The incidences of adverse events were comparable between the two groups. Conclusion: The improvements of Ht SDS, HV, and IGF-1 SDS were more significant in the high-dose group than in the low-dose group (p < 0.05). PEG-rhGH at the dose of 0.14 mg/kg/week was effective and safe for children with GHD. Clinical Trial Registration: clinicaltrials.gov, identifier NCT02908958.

SKP1-like protein, CrSKP1-e, interacts with pollen-specific F-box proteins and assembles into SCF-type E3 complex in 'Wuzishatangju' (Citrus reticulata Blanco) pollen.

S-ribonuclease (S-RNase)-based self-incompatibility (SI) mechanisms have been extensively studied in Solanaceae, Rosaceae and Plantaginaceae. S-RNase-based SI is controlled by two closely related genes, S-RNase and S-locus F-box (SLF), located at a polymorphic S-locus. In the SI system, the SCF-type (SKP1-CUL1-F-box-RBX1) complex functions as an E3 ubiquitin ligase complex for ubiquitination of non-self S-RNase. Pummelo (Citrus grandis) and several mandarin cultivars are suggested to utilize an S-RNase-based SI system. However, the molecular mechanism of the non-S-factors involved in the SI reaction is not straightforward in Citrus. To investigate the SCF-type E3 complex responsible for the SI reaction in mandarin, SLF, SKP1-like and CUL1 candidates potentially involved in the SI reaction of 'Wuzishatangju' (Citrus reticulata Blanco) were identified based on the genome-wide identification and expression analyses. Sixteen pollen-specific F-box genes (CrFBX1-CrFBX16), one pollen-specific SKP1-like gene (CrSKP1-e) and two CUL1 genes (CrCUL1A and CrCUL1B) were identified and cloned from 'Wuzishatangju'. Yeast two-hybrid (Y2H) and in vitro binding assays showed that five CrFBX proteins could bind to CrSKP1-e, which is an ortholog of SSK1 (SLF-interacting-SKP1-like), a non-S-factor responsible for the SI reaction. Luciferase complementation imaging (LCI) and in vitro binding assays also showed that CrSKP1-e interacts with the N-terminal region of both CrCUL1A and CrCUL1B. These results indicate that CrSKP1-e may serve as a functional member of the SCF-type E3 ubiquitin ligase complex in 'Wuzishatangju'.

Predictors and Prevalence of Recovery and Remission for Consumers Discharged from Mental Hospitals in a Chinese Society.

This research study examines the 1 year rate of recovery and remissions for consumers recently discharging from mental hospitals and identifies factors predicting recovery and remissions in the Hong Kong context. By adopting a prospective longitudinal follow-up research design, a cohort of Chinese people discharged from the mental hospitals and participating in a community-based psychosocial program was followed for 1 year. These individuals were assessed by using standardized assessment scales at baseline, 6 months, and 12 months of follow-up. At 1 year follow up, the rates of recovery, functional and symptomatic remission were 8.0%, 23.0% and 79.3% respectively. Logistic regression analyses indicted that: current recovery was significantly predicted by baseline functioning level and achieving open employment, symptomatic remission was significantly predicted by previous symptom severity and having open employment at baseline, while functional remission was significantly predicted by previous functioning level and having open employment. Result indicates that it is more difficult to achieve functional remission and recovery than symptomatic remission for consumers recently discharging from mental hospitals. Also, symptomatic remission is found not a sufficient condition for recovery, while functional remission plays a vital role in recovery. Helping consumers to achieve open employment and improve social functioning are identified as the predicting factors for recovery and functional remission in the local context.

The impact of caregivers on the effectiveness of an early community mental health detection and intervention programme in Hong Kong.

AIM: The prevalence rate of mental illness in Chinese communities is high, but Chinese clients tend to underutilize mental health services. Caregivers may play an important role in mental health early detection and intervention, but few studies have investigated their roles in community mental health services. This study compared the effectiveness of an early detection and intervention programme, the Community Mental Health Intervention Project, for two groups in the context of Hong Kong - clients with and without caregivers. METHOD: A comparison group pre-post-test design was adopted. A total of 170 service users joined this study, including 100 with caregivers and 70 without caregivers. RESULTS: Both groups showed a significant decrease in psychiatric symptoms and increase in community living skills; the group without caregivers indicated a greater reduction in psychiatric symptoms. Different social work intervention components had different predictive effects on these changes. CONCLUSION: The Community Mental Health Intervention Project is an effective early detection and intervention programme in working with Hong Kong Chinese people who are suspected of having mental health problems, especially for those without caregivers.

Validation of the Automatic Thoughts Questionnaire (ATQ) Among Mainland Chinese Students in Hong Kong.

OBJECTIVE: The present study validated the combined version of the 8-item Automatic Thought Questionnaire (ATQ) and 10 positive items from the ATQ-revised among Chinese university students. METHOD: A total of 412 Mainland Chinese university students were recruited in Hong Kong by an online survey. RESULTS: A 14-item Chinese ATQ was derived via item analysis. Satisfactory internal consistency reliability and good split-half reliability were obtained. Exploratory and confirmatory factor analysis revealed a 3-correlated-factor solution for the Chinese ATQ: negative thought, positive thought (emotional), and positive thought (cognitive). The negative ATQ subscale score was positively correlated with negative affect, and negatively correlated with positive affect and life satisfaction. The two positive ATQ subscale scores were negatively correlated with negative affect, and positively correlated with positive affect and life satisfaction. CONCLUSION: The 14-item ATQ is a valid and reliable instrument for measuring automatic thoughts in the Chinese context of Hong Kong.

Ways of coping of Chinese caregivers for family members with schizophrenia in two metropolitan cities: Guangzhou and Hong Kong, China.

BACKGROUND: In Chinese societies, family caregivers play an important role in the recovery of persons with serious mental illness, such as schizophrenia. While family caregivers are often invaluable sources of caregiving in the community, a majority of them lack adequate knowledge and support skills to cope with the tasks involved. AIMS: This study compares the coping strategies and psychological health of caregivers for family members with schizophrenia in two Chinese cities, Hong Kong and Guangzhou. METHOD: A total of 109 caregivers, including 39 from Hong Kong and 70 from Guangzhou, were recruited from non-governmental mental health organizations in the two cities. They were assessed by the Chinese version of the Ways of Coping Questionnaire and the General Health Questionnaire. RESULTS: While there was no significant difference in the psychological distress of the family caregivers in the two locations, the Guangzhou caregivers adopt significantly more of the eight coping strategies, namely, confronting coping, distancing, self-control, seeking social support, accepting responsibility, escape-avoidance, planful problem solving and positive reappraisal, than their counterparts in Hong Kong. Significant correlations were also found between psychological distress and coping strategies of caregivers in the two cities. CONCLUSION: There were significant differences in the coping strategies of family caregivers for people with schizophrenia in the two Chinese cities. Further studies are warranted to investigate factors affecting their coping strategies and their effects on psychological health.

Acculturative stressors and acculturative strategies as predictors of negative affect among Chinese international students in Australia and Hong Kong: a cross-cultural comparative study.

OBJECTIVE: There are few studies comparing cross-cultural adaptation of migrant groups in two different cultural settings. This study compares the level of negative affect and acculturative stressors between Chinese international students in Australia and Mainland Chinese students in Hong Kong. The predictive effects of acculturative stressors and acculturative strategies on negative affect were also compared between the two groups. METHOD: A total of 606 graduate students were recruited for a cross-sectional survey in Melbourne, and Hong Kong, China. The measurement included the Acculturative Hassles Scale for Chinese Students, Acculturative Strategy Scale, and Chinese Affect Scale. Independent t-tests and hierarchical regression analysis were conducted for data analysis. RESULTS: Chinese international students in Australia were found to encounter more acculturative stressors and experience a higher level of negative affect than their counterparts in Hong Kong. The acculturative stressor of academic work and a marginalization strategy significantly predicted negative affect in both groups. The acculturative stressor of cultural difference predicted negative affect in the Hong Kong sample, and assimilation strategy predicted negative affect in the Australian sample only. CONCLUSION: It is more difficult for Chinese international students to adapt to a host society with greater cultural distance. Cross-cultural comparative study helps to find out culture-general and culture-specific predictors of acculturation and helps design tailor-made intervention programs for international students across cultures.

The protective function of meaning of life on life satisfaction among Chinese students in Australia and Hong Kong: a cross-cultural comparative study.

OBJECTIVE: The authors compared the predictive effects of acculturative stressors and meaning of life on life satisfaction between Chinese students in Australia and in Hong Kong. PARTICIPANTS: In 2006, the researchers recruited 606 Chinese students studying abroad at the University of Melbourne in Australia and at 6 universities in Hong Kong. METHODS: Participants completed a questionnaire that included measures of acculturative stressors, meaning of life, life satisfaction, and demographic information. RESULTS: The Australian sample experienced a significantly higher level of acculturative stressors than did the Hong Kong sample, but life satisfaction did not differ significantly between the 2 samples. Meaning of life had a strong positive contribution and acculturative stressors had a negative contribution in predicting life satisfaction in both samples. Meaning of life partially mediated the relationship between acculturative stressors and life satisfaction in both samples. CONCLUSIONS: The authors discuss the theoretical and practical implications for Chinese students studying abroad.

Acculturative stressor and meaning of life as predictors of negative affect in acculturation: a cross-cultural comparative study between Chinese international students in Australia and Hong Kong.

OBJECTIVE: The purpose of the present study was to compare the predictive effects of acculturative stressor and meaning of life on negative affect in the process of acculturation between Chinese international students in Australia and Hong Kong. METHOD: Four hundred mainland Chinese students studying at six universities in Hong Kong and 227 Chinese international students studying at the University of Melbourne in Australia completed a questionnaire that included measures of acculturative stressor, meaning of life, negative affect and demographic information. RESULTS: The Australian sample was found to have a higher level of acculturative stressor and negative affect than the Hong Kong sample. Acculturative stressor had a positive impact on negative affect in both samples, but the impact of different domains of acculturative stressor on negative affect varied between the two groups. Finally, meaning of life partially mediated the relationship between acculturative stressor and negative affect in the Hong Kong sample, but no such effect was found in the Australia sample. CONCLUSIONS: Acculturative stressor is a critical risk factor for negative affect in acculturation for Chinese international students in Australia and Hong Kong. Meaning of life acted as a protective factor that mitigated negative affect for mainland Chinese students in Hong Kong, but not for the Chinese international students in Australia. The theoretical and practical implications for resilience-based and meaning-oriented intervention for Chinese international students are discussed.