Size selection of intrahepatic lesions for cryoablation contributes to abscopal effect and long-term survival in patients with liver metastatic melanoma receiving PD-1 blockade therapy.

OBJECTIVES: In this study, we aimed to examine parameters of cryoablation, tumor characteristics, and their correlations with distant tumor response and survival of liver metastatic melanoma patients receiving cryoablation and PD-1 blockade (cryo-PD-1) combination treatment. MATERIALS AND METHODS: A retrospective study was conducted among 45 melanoma patients who received combined PD-1 blockade therapy and cryoablation for liver metastasis from 2018 to 2022. Cox regression was utilized to determine the associations between factors and overall survival (OS). Changes in cytokines and immune cell compositions in peripheral blood samples following the combined treatment were investigated, along with their correlations with treatment response. RESULTS: The mean cycle of cryo-PD-1 combination treatment was 2.2 (range, 1-6), and the 3-month overall response rate (RECIST 1.1 criteria) was 26.7%. Of the 21 patients who failed previous PD-1 blockade therapy after diagnosis of liver metastasis, 4 (19.0%) achieved response within 3 months since combination treatment. The diameter of ablated lesion ≤ 30 mm, metastatic organs ≤ 2, and pre-treatment LDH level ≤ 300 U/L were independent prognostic factors for favorable OS. Further analysis showed patients with intrahepatic tumor size of 15-45 mm, and ablated lesion size of ≤ 30 mm had significantly higher 3-month response rate (42.9% vs 12.5%; P = 0.022) and survival time (30.5 vs 14.2 months; P = 0.045) than their counterparts. The average increase in NLR among patients with ablated tumor size of ≤ 3 cm and > 3 cm were 3.59 ± 5.01 and 7.21 ± 12.57, respectively. The average increase in serum IL-6 levels among patients with ablated tumor size of ≤ 3 cm and > 3 cm were 8.62 ± 7.95 pg/ml and 15.40 ± 11.43 pg/ml, respectively. CONCLUSION: Size selection of intrahepatic lesions for cryoablation is important in order to achieve abscopal effect and long-term survival among patients with liver metastatic melanoma receiving PD-1 blockade therapy.

An evaluation of dexmedetomidine in combination with midazolam in pediatric sedation: a systematic review and meta-analysis.

BACKGROUND: Dexmedetomidine and midazolam are commonly used sedatives in children. We conducted a systematic review and meta-analysis to compare the safety and effectiveness of sedation provided by dexmedetomidine combined with midazolam versus other sedatives including chloral hydrate, midazolam and other sedatives in pediatric sedation. METHODS: The Embase, Web of Science, Cochrane Library, and PubMed databases, and Clinicaltrials.gov register of controlled trials were searched from inception to June 2022. All randomized controlled trials used dexmedetomidine-midazolam in pediatric sedation were enrolled. The articles search, data extraction, and quality assessment of included studies were performed independently by two researchers. The success rate of sedation was considered as the primary outcome. The secondary outcomes included onset time of sedation, recovery time of sedation and occurrence of adverse events. RESULTS: A total of 522 studies were screened and 6 RCTs were identified; 859 patients were analyzed. The administration of dexmedetomidine combined with midazolam was associated with a higher sedation success rate and a lower incidence of nausea and vomiting in computed tomography, magnetic resonance imaging, Auditory Brainstem Response test or fiberoptic bronchoscopy examinations than the other sedatives did (OR = 2.92; 95% CI: 1.39-6.13, P = 0.005, I2 = 51%; OR = 0.23, 95% CI: 0.07-0.68, P = 0.008, I2 = 0%, respectively). Two groups did not differ significantly in recovery time and the occurrence of adverse reactions (WMD = - 0.27, 95% CI: - 0.93 to - 0.39, P = 0.42; OR 0.70; 95% CI: 0.48-1.02, P = 0.06, I2 = 45%. respectively). However, the results of the subgroup analysis of ASA I-II children showed a quicker onset time in dexmedetomidine-midazolam group than the other sedatives (WMD=-3.08; 95% CI: -4.66 to - 1.49, P = 0.0001, I2 = 30%). CONCLUSIONS: This meta-analysis showed that compared with the control group, dexmedetomidine combined with midazolam group provided higher sedation success rates and caused a lower incidence of nausea and vomiting in completing examinations, indicating a prospective outpatient clinical application for procedural sedation.

Novel insights into the glucose metabolic alterations of freshwater snails: a pathway to molluscicide innovation and snail control strategies.

As ecosystem disruptors and intermediate hosts for various parasites, freshwater snails have significant socioeconomic impacts on human health, livestock production, and aquaculture. Although traditional molluscicides have been widely used to mitigate these effects, their environmental impact has encouraged research into alternative, biologically based strategies to create safer, more effective molluscicides and diminish the susceptibility of snails to parasites. This review focuses on alterations in glucose metabolism in snails under the multifaceted stressors of parasitic infections, drug exposure, and environmental changes and proposes a novel approach for snail management. Key enzymes within the glycolytic pathway, such as hexokinase and pyruvate kinase; tricarboxylic acid (TCA) cycle; and electron transport chains, such as succinate dehydrogenase and cytochrome c oxidase, are innovative targets for molluscicide development. These targets can affect both snails and parasites and provide an important direction for parasitic disease prevention research. For the first time, this review summarises the reverse TCA cycle and alternative oxidase pathway, which are unique metabolic bypasses in invertebrates that have emerged as suitable targets for the formulation of low-toxicity molluscicides. Additionally, it highlights the importance of other metabolic pathways, including lactate, alanine, glycogenolysis, and pentose phosphate pathways, in snail energy supply, antioxidant stress responses, and drug evasion mechanisms. By analysing the alterations in key metabolic enzymes and their products in stressed snails, this review deepens our understanding of glucose metabolic alterations in snails and provides valuable insights for identifying new pharmacological targets.

Improving cascade outcomes for active TB: A global systematic review and meta-analysis of TB interventions.

BACKGROUND: To inform policy and implementation that can enhance prevention and improve tuberculosis (TB) care cascade outcomes, this review aimed to summarize the impact of various interventions on care cascade outcomes for active TB. METHODS AND FINDINGS: In this systematic review and meta-analysis, we retrieved English articles with comparator arms (like randomized controlled trials (RCTs) and before and after intervention studies) that evaluated TB interventions published from January 1970 to September 30, 2022, from Embase, CINAHL, PubMed, and the Cochrane library. Commentaries, qualitative studies, conference abstracts, studies without standard of care comparator arms, and studies that did not report quantitative results for TB care cascade outcomes were excluded. Data from studies with similar comparator arms were pooled in a random effects model, and outcomes were reported as odds ratio (OR) with 95% confidence interval (CI) and number of studies (k). The quality of evidence was appraised using GRADE, and the study was registered on PROSPERO (CRD42018103331). Of 21,548 deduplicated studies, 144 eligible studies were included. Of 144 studies, 128 were from low/middle-income countries, 84 were RCTs, and 25 integrated TB and HIV care. Counselling and education was significantly associated with testing (OR = 8.82, 95% CI:1.71 to 45.43; I2 = 99.9%, k = 7), diagnosis (OR = 1.44, 95% CI:1.08 to 1.92; I2 = 97.6%, k = 9), linkage to care (OR = 3.10, 95% CI = 1.97 to 4.86; I2 = 0%, k = 1), cure (OR = 2.08, 95% CI:1.11 to 3.88; I2 = 76.7%, k = 4), treatment completion (OR = 1.48, 95% CI: 1.07 to 2.03; I2 = 73.1%, k = 8), and treatment success (OR = 3.24, 95% CI: 1.88 to 5.55; I2 = 75.9%, k = 5) outcomes compared to standard-of-care. Incentives, multisector collaborations, and community-based interventions were associated with at least three TB care cascade outcomes; digital interventions and mixed interventions were associated with an increased likelihood of two cascade outcomes each. These findings remained salient when studies were limited to RCTs only. Also, our study does not cover the entire care cascade as we did not measure gaps in pre-testing, pretreatment, and post-treatment outcomes (like loss to follow-up and TB recurrence). CONCLUSIONS: Among TB interventions, education and counseling, incentives, community-based interventions, and mixed interventions were associated with multiple active TB care cascade outcomes. However, cost-effectiveness and local-setting contexts should be considered when choosing such strategies due to their high heterogeneity.

Oral midazolam vs. intranasal dexmedetomidine plus oral midazolam for sedation of pediatric outpatients: a double-blinded randomized controlled trial.

BACKGROUND: Moderate to deep sedation is required for dental treatment of children with dental anxiety. Midazolam is the most commonly used sedative, whereas intranasal dexmedetomidine is increasingly used in pediatric sedation. OBJECTIVE: The aim of this trial was to compare the sedative efficacy of oral midazolam alone with that of intranasal dexmedetomidine plus oral midazolam during dental treatment of children with dental anxiety. DESIGN: In total, 83 children (aged 3-12 years) scheduled to undergo dental sedation were randomized to receive oral midazolam (0.5 mg/kg) and intranasal placebo, or oral midazolam (0.5 mg/kg) plus intranasal dexmedetomidine (2 µg/kg). The primary outcome was the rate of successful sedation for dental treatment. Secondary outcomes were the onset time and adverse events during and after treatment. Data analyses involved descriptive statistics and nonparametric tests. RESULTS: The rate of successful sedation was significantly higher in combination group (P = 0.007), although the sedation onset time was significantly longer in combination group (17.5 ± 2.4 min) than in monotherapy group (15.7 ± 1.8) (P = 0.003). No children required medical intervention or oxygen therapy for hemodynamic disturbances, and the incidences of adverse events had no significant difference between groups (P = 0.660). CONCLUSION: Combined treatment with oral midazolam (0.5 mg/kg) and intranasal dexmedetomidine (2 µg/kg) is more significantly effective for managing the behavior of non-cooperative children during dental treatment, compared to oral midazolam (0.5 mg/kg) alone. (Chinese Clinical Trial Registry: ChiCTR2100042300) TRIAL REGISTRATION: ChiCTR2100042300, Clinical trial first registration date: 17/01/2021.

[Metabolomics study of Berberidis Radix in intervening ulcerative colitis based on UPLC-Q-TOF-MS].

The effect of Tujia medicine Berberidis Radix on endogenous metabolites in the serum and feces of mice with ulcerative colitis(UC) induced by dextran sulfate sodium(DSS) was analyzed by metabolomics technology to explore the metabolic pathway and underlying mechanism of Berberidis Radix in the intervention of UC. The UC model was induced in mice by DSS. Body weight, disease activity index(DAI), and colon length were recorded. The levels of tumor necrosis factor-α(TNF-α) and interleukin-10(IL-10) in colon tissues were determined by ELISA. The levels of endogenous metabolites in the serum and feces were detected by ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS). Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were employed to characterize and screen differential metabolites. The potential metabolic pathways were analyzed by MetaboAnalyst 5.0. The results showed that Berberidis Radix could significantly improve the symptoms of UC mice and increase the level of the anti-inflammatory factor IL-10. A total of 56 and 43 differential metabolites were identified in the serum and feces, respectively, belonging to lipids, amino acids, fatty acids, etc. After the intervention by Berberidis Radix, the metabolic disorder gradually recovered. The involved metabolic pathways included biosynthesis of phenylalanine, tyrosine, and tryptophan, linoleic acid metabolism, phenylalanine metabolism, and glycerophospholipid metabolism. Berberidis Radix can alleviate the symptoms of mice with DSS-induced UC, and the mechanism may be closely related to the re-gulation of lipid metabolism, amino acid metabolism, and energy metabolism.

The relationship between nuclear factor-erythrocyte-related factor 2 and antioxidant enzymes in the placenta of patients with gestational diabetes and the metabolism of umbilical cord endothelial cells.

The paper aimed to explore the relationship between nuclear factor erythroid 2 related factor 2 (Nrf2), antioxidant enzymes and the metabolism of umbilical cord endothelial cells in the placenta of patients with gestational diabetes (GDM). A total of 200 pregnant women who underwent an obstetric examination at the Municipal Maternity and Child Health Hospital from March 2018 to December 2019 were selected, with an average age of 30.91±3.24. According to the plasma glucose level and oral glucose tolerance test (OGTT), pregnant women were divided into a control group and an observation group. Blood samples were collected from these pregnant women, serum was removed, put into a centrifuge tube and stored in the refrigerator of the laboratory at - 80 °C. Placental tissue was collected for biochemical analysis. GSH level was detected by absorbance kit, and serum MDA content was detected by spectrophotometry. The expression levels of Heme oxygenase-1(HO-1), Nrf2, and NQO1 protein in placental tissue were analyzed by gel electrophoresis. Western blot analysis was used to detect the protein expression levels of Bach1 and Keap1 in endothelial cells. PCR real-time analysis was used to detect the expression of GSH and NQO1 mRNA. Results showed that the SOD and GSH levels in the serum of the observation group were lower than those of the control group (P<0.05). The protein expression levels of HO-1, Nrf2 and NQO1 in the observation group were higher than those in the control group (P<0.05). The GSH level of the HNE+ observation group was lower than that of the HNE+ control group before stimulation (P<0.05). 1.5 hours after the stimulation, the GSH levels of the two groups of cells were decreased. After 6 hours, the GSH levels of the two groups began to increase. The GSH level of HUVEC in the HNE+ observation group was lower than that of the HNE+ control group after 48 hours. The expression level of Bach1 protein in the HNE+ observation group was lower than that in the HNE+ control group (P<0.05). The expression level of Keap1 protein in the HNE+ observation group and HNE+ control group did not change (P>0.05). The expression levels of GSH and NQO1 mRNA in the HNE+Nrf2 silence group were lower than that in the Nrf2 silence group (P<0.05). The expression levels of GSH and NQO1 mRNA in the HNE+Nrf2 overexpression observation group were higher than those of the HNE+Nrf2 silence group (P<0.05). The apoptosis of trophoblast in the placenta of GDM patients was significantly decreased. The continuous lack of redox signals in fetal endothelial cells in patients with gestational diabetes can destroy the defense ability of cells in the uterus against oxidative stress. Nrf2 antioxidant defense pathway can provide therapeutic targets for reducing oxidative stress associated with diabetes and aging.

Spatial pattern of the population casualty rate caused by super typhoon Lekima and quantification of the interactive effects of potential impact factors.

BACKGROUND: Typhoons greatly threaten human life and property, especially in China. Therefore, it is important to make effective policy decisions to minimize losses associated with typhoons. METHODS: In this study, the GeoDetector method was used to quantify the determinant powers of natural and socioeconomic factors, and their interactions, on the population casualty rate of super typhoon Lekima. The local indicator of spatial association (LISA) method was followed to explore the spatial pattern of the population casualty rate under the influence of the identified dominant factors. RESULTS: Both natural and socioeconomic factors were found to have significantly impacted the population casualty rate due to super typhoon Lekima. Among the selected factors, maximum precipitation was dominant factor (q = 0.56), followed by maximum wind speed (q = 0.45). In addition, number of health technicians (q = 0.35) and number of health beds (q = 0.27) have a strong influence on the population casualty rate. Among the interactive effects of 12 influencing factors, the combined effects of maximum precipitation and ratio of brick-wood houses, the maximum precipitation and ratio of steel-concrete houses, maximum precipitation and number of health technicians were highest (q = 0.72). Furthermore, high-risk areas with very high casualty rates were concentrated in the southeastern part of Zhejiang and northern Shandong Provinces, while lower-risk areas were mainly distributed in northern Liaoning and eastern Jiangsu provinces. CONCLUSIONS: These results contribute to the development of more specific policies aimed at safety and successful property protection according to the regional differences during typhoons.

Syphilis Self-testing: A Nationwide Pragmatic Study Among Men Who Have Sex With Men in China.

BACKGROUND: Syphilis self-testing may help expand syphilis testing among men who have sex with men (MSM). China has rapidly scaled up human immunodeficiency virus (HIV) self-testing, creating an opportunity for integrated syphilis self-testing. However, there is a limited literature on implementing syphilis self-testing. METHODS: A cross-sectional online survey was conducted among Chinese MSM in 2018. Participants completed a survey instrument including sociodemographic characteristics, sexual behaviors, syphilis self-testing, and HIV self-testing history. Multivariable logistic regression was conducted to identify correlates of syphilis self-testing. We also recorded potential harms associated with syphilis self-testing. RESULTS: Six hundred ninety-nine MSM from 89 cities in 21 provinces in China completed the study. A total of 361/699 (51.7%) men tested for syphilis, of whom 174/699 (24.9%) men used syphilis self-testing. Among 174 who had self-tested, 90 (51.7%) reported that the self-test was their first syphilis test and 161 (92.5%) reported that they undertook syphilis self-testing together with HIV self-testing. After adjusting for covariates, syphilis self-testing was correlated with disclosure of sexual orientation to family or friends (adjusted odds ratio [aOR], 1.90; 95% confidence interval [CI], 1.32-2.73), reporting 2-5 male sexual partners (aOR, 1.81; 95% CI, 1.04-3.16), HIV self-testing (aOR, 39.90; 95% CI, 17.00-93.61), and never tested for syphilis in the hospital (aOR, 2.96; 95% CI, 1.86-4.72). Self-reported harms associated with syphilis self-testing were minimal. CONCLUSIONS: Scaling up syphilis self-testing could complement facility-based testing in China among MSM. Self-testing may increase first-time testing and has limited harms. Our findings suggest that syphilis self-testing could be integrated into HIV self-testing services.

Risk attitudes, risky sexual behaviours and willingness to test negative for syphilis using lottery-based financial incentives among Chinese men who have sex with men.

BACKGROUND: Individuals with risk-loving attitudes may be more likely to participate in high-risk sex and gambling. We investigated whether a lottery-based financial incentive to have a negative syphilis test may attract Chinese men who have sex with men (MSM) who practised risky sexual behaviours. METHODS: In July 2018, a national online cross-sectional survey was conducted in China. We collected information on willingness to participate in a lottery-based financial incentive where men were eligible if they tested negative for syphilis, and the minimum prize that would attract them to participate. We used a validated risk attitude scale which asked about the willingness to take risks in six domains, ranging from 0 (avoids taking risk) to 10 (fully prepared to take risks). To avoid multicollinearity, we used principal components analysis to create a 'risk attitude index'. Bivariable and multivariable logistic regression explored factors associated with willingness to test negative for syphilis. RESULTS: 699 MSM enrolled with a median age of 26 years (IQR: 23-30). 70% self-identified as gay and 52% reported ever testing for syphilis. 64% stated they were likely or very likely to test for syphilis linked with a lottery-based incentive. The median desired amount for the lottery had an expected value of ¥10 (US$1.50, IQR: ¥5-¥30). Men who had greater odds of willingness to participate in the lottery-based incentive were those scoring highest on the risk attitude index (adjusted OR (AOR) 2.6, 95% CI 1.5 to 4.3), those reporting more than one sexual partner in the last 3 months (AOR 1.7, 95% CI 1.2 to 2.4), those who had not used condoms during their last sex (AOR 1.5, 95% CI 1.0 to 2.2) and those who ever had group sex (AOR 1.5, 95% CI 1.0 to 2.2). CONCLUSION: Chinese MSM with higher risk attitudes and who reported riskier sexual behaviours indicated greater interest in the concept of a lottery-based incentive for syphilis testing. A lottery-based incentive may be a promising strategy for promoting condom use among risk-loving men.

Promoting routine syphilis screening among men who have sex with men in China: study protocol for a randomised controlled trial of syphilis self-testing and lottery incentive.

BACKGROUND: Men who have sex with men (MSM) bear a high burden of syphilis infection. Expanding syphilis testing to improve timely diagnosis and treatment is critical to improve syphilis control. However, syphilis testing rates remain low among MSM, particularly in low- and middle-income countries. We describe the protocol for a randomised controlled trial (RCT) to assess whether provision of syphilis self-testing services can increase the uptake of syphilis testing among MSM in China. METHODS: Four hundred forty-four high-risk MSM will be recruited online and randomized in a 1:1:1 ratio to (1) standard syphilis self-testing arm; (2) a self-testing arm program enhanced with crowdsourcing and a lottery-based incentive, and (3) a standard of care (control). Self-testing services include a free syphilis self-test kit through the mail at monthly intervals. Participants in the lottery incentive arm will additionally receive health promotion materials generated from an open crowdsourcing contest and be given a lottery draw with a 10% chance to win 100 RMB (approximately 15 US Dollars) upon confirmed completion of syphilis testing. Syphilis self-test kits have step-by-step instructions and an instructional video. This is a non-blinded, open-label, parallel RCT. Participants in each arm will be followed-up at three and 6 months through WeChat (a social media app like Facebook messenger). Confirmation of syphilis self-test use will be determined by requiring participants to submit a photo of the used test kit to study staff via secure data messaging. Both self-testing and facility-based testing will be ascertained by sending a secure photographic image of the completed kit through an existing digital platform. The primary outcome is the proportion of participants who tested for syphilis in the past 3 months. DISCUSSION: Findings from this study will provide much needed insight on the impact of syphilis self-testing on promoting routine syphilis screening among MSM. The findings will also contribute to our understanding of the safety, effectiveness and acceptability of syphilis self-testing. These findings will have important implications for self-testing policy, both in China and internationally. TRIAL REGISTRATION: ChiCTR1900022409 (10 April, 2019).

Lay health supporters aided by mobile text messaging to improve adherence, symptoms, and functioning among people with schizophrenia in a resource-poor community in rural China (LEAN): A randomized controlled trial.

BACKGROUND: Schizophrenia is a leading cause of disability, and a shift from facility- to community-based care has been proposed to meet the resource challenges of mental healthcare in low- and middle-income countries. We hypothesized that the addition of mobile texting would improve schizophrenia care in a resource-poor community setting compared with a community-based free-medicine program alone. METHODS AND FINDINGS: In this 2-arm randomized controlled trial, 278 community-dwelling villagers (patient participants) were randomly selected from people with schizophrenia from 9 townships of Hunan, China, and were randomized 1:1 into 2 groups. The program participants were recruited between May 1, 2015, and August 31, 2015, and the intervention and follow-up took place between December 15, 2015, and July 1, 2016. Baseline characteristics of the 2 groups were similar. The patients were on average 46 years of age, had 7 years of education, had a duration of schizophrenia of 18 years with minimal to mild symptoms and nearly one-fifth loss of functioning, and were mostly living with family (95%) and had low incomes. Both the intervention and the control groups received a nationwide community-based mental health program that provided free antipsychotic medications. The patient participants in the intervention group also received LEAN (Lay health supporters, E-platform, Award, and iNtegration), a program that featured recruitment of a lay health supporter and text messages for medication reminders, health education, monitoring of early signs of relapses, and facilitated linkage to primary healthcare. The primary outcome was medication adherence (proportion of dosages taken) assessed by 2 unannounced home-based pill counts 30 days apart at the 6-month endpoint. The secondary and other outcomes included patient symptoms, functioning, relapses, re-hospitalizations, death for any reason, wandering away without notifying anyone, violence against others, damaging goods, and suicide. Intent-to-treat analysis was used. Missing data were handled with multiple imputations. In total, 271 out of 278 patient participants were successfully followed up for outcome assessment. Medication adherence was 0.48 in the control group and 0.61 in the intervention group (adjusted mean difference [AMD] 0.12 [95% CI 0.03 to 0.22]; p = 0.013; effect size 0.38). Among secondary and other outcomes we noted substantial reduction in the risk of relapse (26 [21.7%] of 120 interventional participants versus 40 [34.2%] of 117 controls; relative risk 0.63 [95% CI 0.42 to 0.97]; number needed to treat [NNT] 8.0) and re-hospitalization (9 [7.3%] of 123 interventional participants versus 25 [20.5%] of 122 controls; relative risk 0.36 [95% CI 0.17 to 0.73]; NNT 7.6). The program showed no statistical difference in all other outcomes. During the course of the program, 2 participants in the intervention group and 1 in the control group died. The limitations of the study include its lack of a full economic analysis, lack of individual tailoring of the text messages, the relatively short 6-month follow-up, and the generalizability constraint of the Chinese context. CONCLUSIONS: The addition of texting to patients and their lay health supporters in a resource-poor community setting was more effective than a free-medicine program alone in improving medication adherence and reducing relapses and re-hospitalizations. Future studies may test the effectiveness of customization of the texting to individual patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-ICR-15006053.

Utilization of healthcare services among Chinese migrants in Kenya: a qualitative study.

BACKGROUND: The number of Chinese migrants in Sub-Saharan Africa (SSA) is increasing, which is part of the south-south migration. The healthcare seeking challenges for Chinese migrants in Africa are different from local people and other global migrants. The aim of this study is to explore utilization of local health services and barriers to health services access among Chinese migrants in Kenya. METHODS: Thirteen in-depth interviews (IDIs) and six focus group discussions (FGDs) were conducted among Chinese migrants (n = 32) and healthcare-related stakeholders (n = 3) in Nairobi and Kisumu, Kenya. Data was collected, transcribed, translated, and analyzed for themes. RESULTS: Chinese migrants in Kenya preferred self-treatment by taking medicines from China. When ailments did not improve, they then sought care at clinics providing Traditional Chinese Medicine (TCM) or received treatment at Kenyan private healthcare facilities. Returning to China for care was also an option depending on the perceived severity of disease. The main supply-side barriers to local healthcare utilization by Chinese migrants were language and lack of health insurance. The main demand-side barriers included ignorance of available healthcare services and distrust of local medical care. CONCLUSIONS: Providing information on quality healthcare services in Kenya, which includes Chinese language translation assistance, may improve utilization of local healthcare facilities by Chinese migrants in the country.

Identification of the C-terminal domain of Daxx acts as a potential regulator of intracellular cholesterol synthesis in HepG2 cells.

Daxx is a highly conserved nuclear transcriptional factor, which has been implicated in many nuclear processes including transcription and cell cycle regulation. Our previous study demonstrated Daxx also plays a role in regulation of intracellular cholesterol content. Daxx contains several domains that are essential for interaction with a growing number of proteins. To delineate the underlying mechanism of hypocholesterolemic activity of Daxx, we constructed a set of plasmids which can be used to overexpress different fragments of Daxx and transfected to HepG2 cells. We found that the C- terminal region Daxx626-740 clearly reduced intracellular cholesterol levels and inhibited the expression of SREBPs and SCAP. In GST pull-down experiments and Double immunofluorescence assays, Daxx626-740 was demonstrated to bind directly to androgen receptor (AR). Our findings suggest that the interaction of Daxx626-740 and AR abolishes the AR-mediated activation of SCAP/SREBPs pathway, which suppresses the de novo cholesterol synthesis. Thus, C-terminal domain of Daxx acts as a potential regulator of intracellular cholesterol content in HepG2 cells.

Does mobile phone ownership predict better utilization of maternal and newborn health services? a cross-sectional study in Timor-Leste.

BACKGROUND: Increasingly popular mobile health (mHealth) programs have been proposed to promote better utilization of maternal, newborn and child health services. However, women who lack access to a mobile phone are often left out of both mHealth programs and research. In this study, we determine whether household mobile phone ownership is an independent predictor of utilization of maternal and newborn health services in Timor-Leste. METHODS: The study included 581 women aged 15-49 years with a child under the age of two years from the districts of Manufahi and Ainaro in Timor-Leste. Participants were interviewed via a structured survey of knowledge, practices, and coverage of maternal and child health services, with additional questions related to ownership and utilization of mobile phones. Mobile phone ownership was the exposure variable, and the dependent variables included having at least four antenatal care visits, skilled birth attendance, health facility delivery, a postnatal checkup within 24 h, and a neonatal checkup within 24 h for their youngest child. Logistic regression models were applied to assess for associations. RESULTS: Sixty-seven percent of women reported having at least one mobile phone in the family. Women who had a mobile phone were significantly more likely to be of higher socioeconomic status and to utilize maternal and newborn health services. However, after adjusting socioeconomic factors, household mobile phone ownership was not independently associated with any of the dependent variables. CONCLUSION: Evaluations of the effects of mHealth programs on health in a population need to consider the likelihood of socioeconomic differentials indicated by mobile phone ownership.

Efficacy and safety of GLP-1RAs for people with obesity: A systematic review based on RCT and Bayesian network meta-analysis.

BACKGROUND: GLP-1 receptor agonists (GLP-1RAs) reduce glucagon and glycogen secretion, inhibit appetite and slow gastric empties and have recently been approved to treat obesity. OBJECTIVE: To explore the safety and efficacy of GLP-1RAs in the treatment of obesity and clarify the optimal GLP-1RAs treatment regimen. METHODS: PubMed, Embase, Web of Science, and Cochrane Library databases were searched for English randomized controlled trials (RCTs) on GLP-1RAs in the treatment and management of obesity published before July 18, 2023. Literature screening and data extraction were performed independently by three researchers. Bayesian random effect model was used to compare the effects of interventions. Continuous variables were expressed as mean difference with 95% CI, and dichotomous variables were reported as RR with 95% CI. RESULTS: A total of 29 studies with 10,333 participants were included in the present study. The combination of cagrilintide and semaglutide (short for cagrANDsema) was an optimal strategy for weight loss and glycosylated hemoglobin (HbA1c) reduction. Compared to placebo, cagrANDsema reduced weight by - 14.13 kg (95% CI: -16.49, -11.73) and HbA1c by - 0.33% (95% CI: -0.41, -0.25). Moreover, this study indicated that orforglipron and semaglutide also had relatively good effects on weight loss. Meta-regression results indicated that higher dose levels might have better effects on weight loss. CONCLUSIONS: CagrANDsema exerts the best effect for weight loss. In terms of current dose levels, a higher dose gets better weight-loss effects without increasing the risk of adverse events.

Exploring the spatial pattern of house collapse rates caused by extreme rainfall in central China: The role of natural and social factors.

The collapse of houses represents a prominent hazard associated with floods, mudslides, and other disastrous events resulting from extreme rainfall. Nevertheless, previous research in this area has been insufficiently dedicated to comprehending the factors that specifically contribute to house collapse triggered by extreme rainfall. This study endeavors to address this knowledge gap by proposing a hypothesis that the occurrence of house collapse, induced by extreme rainfall, demonstrates spatial heterogeneity and is subject to the interactive impacts of various factors. In the study, we investigate the relationship between house collapse rates and natural and social factors in the provinces of Henan, Shanxi, and Shaanxi provinces in 2021. These provinces are representative of flood-prone areas in central China. Spatial scan statistics and GeoDetector model were used to analyze spatial hotspot areas of house collapse rates and determinant power of natural and social factors on the spatial heterogeneity of house collapse rates, respectively. Our analysis reveals that the spatial hotspot areas predominantly concentrated in regions characterized by high rainfall, including areas along riverbanks and low-lying regions. Multiple factors contribute to the variations in house collapse rates. Among these factors, precipitation (q = 0.32) is the most significant, followed by the ratio of brick-concrete houses (q = 0.24), per capita GDP (q = 0.13), elevation (q = 0.13) and other factors. Notably, the interaction of precipitation and slope explains 63 % of the damage pattern, making it the strongest causal factor. The results substantiate our initial hypothesis and underscore the fact that the pattern of damage does not solely rely on a singular factor but rather on the interaction of multiple factors. These findings hold significance in advancing the formulation of more precise strategies aimed at bolstering safety measures and safeguarding properties within regions susceptible to flooding.

Interactions between Orthodontic Treatment and Gingival Tissue.

In recent years, as the number of adults seeking orthodontic treatment has increased, so too has the number of periodontal tissue problems, particularly regarding the impact on periodontal tissue of receiving orthodontic treatment. Orthodontic treatment improves the occlusion and appearance of teeth by moving the teeth appropriately. These movements have a significant impact on the interactions between the teeth and periodontal tissues. Orthodontic treatment can also recover tooth alignment for patients with tooth displacement caused by periodontitis; however, orthodontic treatment also often has adverse effects on periodontal soft tissue, such as gingivitis, gingival enlargement and gingival recession. The purpose of this review is to summarise the current evidence and solid knowledge of periodontal soft tissue problems in orthodontic treatment and outline some prevention strategies.

Berberine attenuates uric acid-induced cell injury by inhibiting NLRP3 signaling pathway in HK-2 cells.

Hyperuricemia (HUA) is a common chronic metabolic disease that can cause renal failure and even death in severe cases. Berberine (BBR) is an isoquinoline alkaloid derived from Phellodendri Cortex with strong antioxidant, anti-inflammatory, and anti-apoptotic properties. The purpose of this study was to investigate the protective effects of berberine (BBR) against uric acid (UA)-induced HK-2 cells and unravel their regulatory potential mechanisms. The CCK8 assay was carried out to detect cell viability. The expression levels of inflammatory factors interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) and Lactate dehydrogenase (LDH) were measured using Enzyme-linked immunosorbent assays (ELISA). The expression of the apoptosis-related protein (cleaved-Caspase3, cleaved-Caspase9, BAX, BCL-2) was detected by western blot. The effects of BBR on the activities of the NOD-like receptor family pyrin domain containing 3 (NLRP3) and the expression of the downstream genes were determined by RT-PCR and western blot in HK-2 cells. From the data, BBR significantly reversed the up-regulation of inflammatory factors (IL-1ß, IL-18) and LDH. Furthermore, BBR down-regulated protein expression of pro-apoptotic proteins BAX, cleaved caspase3 (cl-Caspase3), cleaved caspase9 (cl-Caspase9), and enhanced the expression of antiapoptotic protein BCL-2. Simultaneously, BBR inhibited the activated NLPR3 and reduced the mRNA levels of NLRP3, Caspase1, IL-18, and IL-1ß. Also, BBR attenuated the expression of NLRP3 pathway-related proteins (NLRP3, ASC, Caspase1, cleaved-Caspase1, IL-18, IL-1ß, and GSDMD). Furthermore, specific NLRP3-siRNA efficiently blocked UA-induced the level of inflammatory factors (IL-1ß, IL-18) and LDH and further inhibited activated NLRP3 pathway. Collectively, our results suggested that BBR can alleviate cell injury induced by UA. The underlying unctionary mechanism may be through the NLRP3 signaling pathway.

Vulnerability to typhoons: A comparison of consequence and driving factors between Typhoon Hato (2017) and Typhoon Mangkhut (2018).

Typhoon disasters have caused casualties, property loss, and other negative impacts to social and economic development. Vulnerability is an important component of typhoon risk. However, little is known about the contributions of vulnerability factors and their interaction effects on typhoon-induced losses at a fine scale. Focusing on the vulnerability measures of Typhoon Hato in 2017 and Typhoon Mangkhut in 2018, this study aims to quantify the contribution and interactive effects of physical and socioeconomic factors on vulnerability based on the GeoDetector method and determine the factors that account for most of the change in vulnerability. The results show that from Typhoon Hato in 2017 to Typhoon Mangkhut in 2018, the vulnerability of the economy and houses decrease on average. Rain intensity and wind intensity are the dominant factors of disaster loss for Typhoon Hato and Typhoon Mangkhut, respectively. Vegetation cover and landform explain vulnerability better than average slope in most instances. For different loss types, the dominant socioeconomic vulnerability factor is different. For both typhoons, emergency transfer has a higher determining power (q) ranking for the population vulnerability, while the percentage of the GDP made up of primary industry have higher q ranking for economic vulnerability. The dominant interaction effects between two vulnerability factors differ depending on the typhoon and loss type but show a nonlinear enhancement effect in most cases. Moreover, changes in the maximum 4-hour accumulated rainfall account for most of the change in vulnerability between Hato and Mangkhut. Overall, the results can be conducive to understanding the complexity of vulnerability to typhoons and provide a reference for possible indicators for vulnerability assessment models, and determining the reasons for changes in vulnerability can be constructive to the formulation of specific policies for disaster prevention and mitigation.