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With political will, modest financial investment and effective technical assistance, public sector hepatitis C virus (HCV) programmes can be established in low- and middle-income countries as a first step towards elimination. Seven countries, with support from the Clinton Health Access Initiative (CHAI) and partners, have expanded access to HCV treatment by combining programme simplification with market shaping to reduce commodity prices. CHAI has supported a multipronged approach to HCV programme launch in Cambodia, India, Indonesia, Myanmar, Nigeria, Rwanda and Vietnam including pricing negotiations with suppliers, policy development, fast-track registrations of quality-assured generics, financing advocacy and strengthened service delivery. Governments are leading programme implementation, leveraging HIV programme infrastructure/financing and focusing on higher-HCV prevalence populations like people living with HIV, people who inject drugs and prisoners. This manuscript aims to describe programme structure and strategies, highlight current commodity costs and outline testing and treatment volumes across these countries. Across countries, commodity costs have fallen from >US$100 per diagnostic test and US$750–US$900 per 12-week pan-genotypic direct-acting antiviral regimen to as low as US$80 per-cure commodity package, including WHO-prequalified generic drugs (sofosbuvir + daclatasvir). As of December 2019, 5900+ healthcare workers were trained, 2 209 209 patients were screened, and 120 522 patients initiated treatment. The cure (SVR12) rate was >90%, including at lower-tier facilities. Programmes are successfully implementing simplified, decentralised public health approaches. Combined with political will and affordable pricing, these efforts can translate into commitments to achieve global targets. However, to achieve elimination, additional investment in scale-up is required.

Epigenetic regulation of key transcriptional programs is a critical mechanism that controls hematopoietic development, and, thus, aberrant expression patterns or mutations in epigenetic regulators occur frequently in hematologic malignancies. We demonstrate that the Polycomb protein L3MBTL1, which is monoallelically deleted in 20q- myeloid malignancies, represses the ability of stem cells to drive hematopoietic-specific transcriptional programs by regulating the expression of SMAD5 and impairing its recruitment to target regulatory regions. Indeed, knockdown of L3MBTL1 promotes the development of hematopoiesis and impairs neural cell fate in human pluripotent stem cells. We also found a role for L3MBTL1 in regulating SMAD5 target gene expression in mature hematopoietic cell populations, thereby affecting erythroid differentiation. Taken together, we have identified epigenetic priming of hematopoietic-specific transcriptional networks, which may assist in the development of therapeutic approaches for patients with anemia.

Cell-derived extracellular vesicles (EVs) are being actively explored as a novel acellular approach to heart failure. Accumulating evidence suggests EVs improve cardiac function in non-ischemic heart failure, but the strength and consistency of this effect is unknown. As such, we critically appraised the preclinical literature supporting the ability of EVs to improve cardiac function in animal models of non-ischemic heart failure. After a systematic search that yielded 18 studies, we determined the overall effect of EV treatment on left ventricular function and performed regression analysis to identify EV effects on clinically relevant parameters. EV treatment uniformly improved ejection fraction (2.41 [95% CI: 1.76, 3.06; p < 0.00001; I2 = 46%]) and fractional shortening (2.22 [95% CI: 1.40, 3.05; p < 0.00001; I2 = 56%]) as compared to untreated control animals. Secondary outcomes (such as left ventricular volumes or myocardial fibrosis) were similarly improved in EV treated animals. Although the number of studies included in the analysis was modest, there was no evidence for a publication bias. In conclusion, EV treatment improves cardiac function in preclinical models of non-ischemic heart failure. Although EVs originated from dissimilar cell lines and were applied to a variety of different animal models, we observed a consistent improvement in cardiac function suggesting application of EVs to non-ischemic heart failure has merit and warrants future attention.

Background and Aim: Rabies is a zoonotic disease that persists endemic in numerous countries worldwide. In Vietnam, the main sources of rabies are dogs and cats, and they caused 76 human deaths annually by 2017–2021. Long An province has recently experienced an increasing burden of rabies, with seven fatal cases reported in the past 5 years. Various rabies control measures have been implemented in this province, including mass vaccination of the animal population, post-vaccination monitoring, diagnostic testing of suspected rabid dogs, dog bite investigation, animal management, pre-exposure treatment, post-exposure treatment (PET), and awareness programs. This study aimed to estimate the cost of rabies control measures for animals and humans in Long An province in 2022. Materials and Methods: An economic model was developed to estimate the costs of rabies control under two scenarios, with and without external financial support from the private sector. Inputs for the model included data from published literature, publicly available reports on rabies, government data, expert opinions, and a pilot study conducted in Vietnam. Results: The total annual costs of rabies control, with or without external support, were estimated to be VND 62.62 and 62.77 billion (equivalent to USD 2.67 and 2.68 million), respectively. The highest proportion of costs was related to PET in humans (84.50% and 84.30%), followed by the cost of mass vaccination paid by animal owners (14.28% and 13.90%). Most of the expenses were paid by the private sector (98.87% and 98.98%) rather than the public sector (1.14% and 1.20%). Conclusion: This study described a transparent and reproducible method for estimating the economic costs of rabies control at the provincial level. The economic model developed showed that control of rabies by mass vaccination is more cost-effective than using PET to prevent human death. The model can be applied to future economic analyses of rabies control in other provinces of Vietnam and other rabies-endemic countries.

Song-Xing Wang,1,2,&ast; Li-Yan Sun,3,&ast; Qiong Yu,2 Ran Li,4 Yun-Ping Xu,3 Jin-Feng Zeng4 1Clinical Laboratory, The Third People’s Hospital of Longgang District, Shenzhen, People’s Republic of China; 2Quality Control Department, Shenzhen Blood Center, Shenzhen, People’s Republic of China; 3Institution of Transfusion Medicine, Shenzhen Blood Center, Shenzhen, People’s Republic of China; 4Clinical Laboratory, Shenzhen Blood Center, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yun-Ping Xu; Jin-Feng Zeng, Email yunpingxu1982@hotmail.com; zzengjf@163.comBackground: In Shenzhen of China, the continuous increase of syphilis infections threatens the safety of blood transfusion. In 2020, COVID-19 was discovered and spread rapidly around the world, and affected the prevalence of syphilis among blood donors.Methods: From 2013 to 2020, there were 839,161 blood samples collected in the Shenzhen Blood Center. Blood samples were screened by ELISA tests and confirmed by the TPPA (Treponema pallidum particle agglutination) tests and the TRUST (toluidine red unheated serum tests). All data was analyzed by the chi-square test.Results: From 2013 to 2020, the positive rate of syphilis among blood donors varied significantly among individuals in different ages, educational backgrounds, regions, and blood donation histories (P< 0.001). In 2020, It was the first time that there were more repeat blood donors than first-time blood donors and more blood donors with a higher education level than those with a lower education level, and the lowest reactive and positive rate of syphilis among blood donors was observed. Compared to 2019, the prevalence of syphilis among female and repeat blood donors decreased significantly in 2020 (P< 0.01).Conclusion: The prevalence of syphilis in blood donors is related to the characteristics of blood donors (in addition to gender) and the COVID-19 epidemic. COVID-19 can affect the prevalence of syphilis among blood donors by influencing the composition of blood donors and the number of syphile-positive donors in certain blood donors, including female and repeat blood donors.Keywords: syphilis, COVID-19, blood donors

Abstract Background Use of electronic health records (EHR) to provide real-world data for research is established, but using EHR to deliver randomised controlled trials (RCTs) more efficiently is less developed. The Allergy AntiBiotics And Microbial resistAnce (ALABAMA) RCT evaluated a penicillin allergy assessment pathway versus usual clinical care in a UK primary care setting. The aim of this paper is to describe how EHRs were used to facilitate efficient delivery of a large-scale randomised trial of a complex intervention embracing efficient participant identification, supporting minimising GP workload, providing accurate post-intervention EHR updates of allergy status, and facilitating participant follow up and outcome data collection. The generalisability of the EHR approach and health economic implications of EHR in clinical trials will be reported in the main ALABAMA trial cost-effectiveness analysis. Methods A descriptive account of the adaptation of functionality within SystmOne used to deliver/facilitate multiple trial processes from participant identification to outcome data collection. Results An ALABAMA organisation group within SystmOne was established which allowed sharing of trial functions/materials developed centrally by the research team. The ‘ALABAMA unit’ within SystmOne was also created and provided a secure efficient environment to access participants’ EHR data. Processes of referring consented participants, allocating them to a trial arm, and assigning specific functions to the intervention arm were developed by adapting tools such as templates, reports, and protocols which were already available in SystmOne as well as pathways to facilitate allergy de-labelling processes and data retrieval for trial outcome analysis. Conclusions ALABAMA is one of the first RCTs to utilise SystmOne EHR functionality and data across the RCT delivery, demonstrating feasibility and applicability to other primary care RCTs. Trial registration ClinicalTrials.gov: NCT04108637, registered 05/03/2019. ISRCTN: ISRCTN20579216.

Abstract Background Endometrial preparation significantly influences the success of embryo transfer procedures. Although both oral and transdermal estradiol are common methods for endometrial priming, their efficacy and potential side effects remain uncertain. This randomized controlled trial aims to compare the effectiveness of oral and transdermal estradiol in endometrial preparation, while also evaluating their respective side effects in patients undergoing assisted reproduction treatments. Method This randomized clinical trial (ISRCTN15301227) was conducted at Hung Vuong Hospital between July 2020 and March 2022. Among 550 eligible patients undergoing frozen embryo transfer cycles, we included 380 patients for the study. The study protocol and all materials received approval from the Ethics Committee of Hung Vuong Hospital (1315/CN-HĐĐĐ). Participants were randomly assigned to one of two groups: Group A (n =190) received oral estradiol at an initial dose of 4 mg per day for 7 days, with the dose increased according to clinical response. Group B (n =190) received transdermal estradiol at an initial dose of 2 measures of 2.5 g estradiol gel per day for 7 days, with the dose similarly increased according to clinical response. Treatment in both groups began on days 2–3 of the menstrual cycle, with the maximum duration of estradiol administration being 27 days. We compared estradiol levels on the day of progesterone administration, duration of treatment, total estradiol dose, endometrial thickness, pregnancy outcomes, and any observed side effects between the two groups. Results Group A exhibited significantly higher estradiol levels on the day of progesterone administration compared to Group B (270.5 pg/ml versus 186.5 pg/ml, p

Chang-Sheng Ma,1,2,&ast; Ya-Ping Ma,1,3,&ast; Bo Han,1,2,&ast; Wan-Li Duan,1 Shu-Chen Meng,1 Min Bai,1 Hao Dong,1 Li-Ying Zhang,1 Meng-Yuan Duan,1,2 Jing Liu,1 Ai-Jun Deng,2 Mao-Tao He1,2 1Department of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong, People’s Republic of China; 2Department of Ophthalmology, Affiliated Hospital of Shandong Second Medical University, Weifang, People’s Republic of China; 3Department of Pathology, The 942Hospital of the People’s Liberation Army Joint Logistic Support Force, Yinchuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mao-Tao He, Department of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong, People’s Republic of China, Tel +86-18209617186, Fax +86-0536-3081201, Email hemaotao@sdsmu.edu.cn Ai-Jun Deng, Department of Ophthalmology, Affiliated Hospital of Shandong Second Medical University, Weifang, People’s Republic of China, Email dengaijun@hotmail.comPurpose: Ischemic stroke is a refractory disease wherein the reperfusion injury caused by sudden restoration of blood supply is the main cause of increased mortality and disability. However, current therapeutic strategies for the inflammatory response induced by cerebral ischemia-reperfusion (I/R) injury are unsatisfactory. This study aimed to develop a functional nanoparticle (MM/ANPs) comprising apelin-13 (APNs) encapsulated in macrophage membranes (MM) modified with distearoyl phosphatidylethanolamine-polyethylene glycol-RVG29 (DSPE-PEG-RVG29) to achieve targeted therapy against ischemic stroke.Methods: MM were extracted from RAW264.7. PLGA was dissolved in dichloromethane, while Apelin-13 was dissolved in water, and CY5.5 was dissolved in dichloromethane. The precipitate was washed twice with ultrapure water and then resuspended in 10 mL to obtain an aqueous solution of PLGA nanoparticles. Subsequently, the cell membrane was evenly dispersed homogeneously and mixed with PLGA-COOH at a mass ratio of 1:1 for the hybrid ultrasound. DSPE-PEG-RVG29 was added and incubated for 1 h to obtain MM/ANPs.Results: In this study, we developed a functional nanoparticle delivery system (MM/ANPs) that utilizes macrophage membranes coated with DSPE-PEG-RVG29 peptide to efficiently deliver Apelin-13 to inflammatory areas using ischemic stroke therapy. MM/ANPs effectively cross the blood-brain barrier and selectively accumulate in ischemic and inflamed areas. In a mouse I/R injury model, these nanoparticles significantly improved neurological scores and reduced infarct volume. Apelin-13 is gradually released from the MM/ANPs, inhibiting NLRP3 inflammasome assembly by enhancing sirtuin 3 (SIRT3) activity, which suppresses the inflammatory response and pyroptosis. The positive regulation of SIRT3 further inhibits the NLRP3-mediated inflammation, showing the clinical potential of these nanoparticles for ischemic stroke treatment. The biocompatibility and safety of MM/ANPs were confirmed through in vitro cytotoxicity tests, blood-brain barrier permeability tests, biosafety evaluations, and blood compatibility studies.Conclusion: MM/ANPs offer a highly promising approach to achieve ischemic stroke-targeted therapy inhibiting NLRP3 inflammasome-mediated pyroptosis. Keywords: apelin-13, cerebral ischemia-reperfusion injury, macrophage membrane, ischemic stroke therapy, pyroptosis

Abstract Introduction Digital mental health interventions (DMHIs) overcome traditional barriers enabling wider access to mental health support and allowing individuals to manage their treatment. How individuals engage with DMHIs impacts the intervention effect. This review determined whether the impact of user engagement was assessed in the intervention effect in Randomised Controlled Trials (RCTs) evaluating DMHIs targeting common mental disorders (CMDs). Methods This systematic review was registered on Prospero (CRD42021249503). RCTs published between 01/01/2016 and 17/09/2021 were included if evaluated DMHIs were delivered by app or website; targeted patients with a CMD without non-CMD comorbidities (e.g., diabetes); and were self-guided. Databases searched: Medline; PsycInfo; Embase; and CENTRAL. All data was double extracted. A meta-analysis compared intervention effect estimates when accounting for engagement and when engagement was ignored. Results We identified 184 articles randomising 43,529 participants. Interventions were delivered predominantly via websites (145, 78.8%) and 140 (76.1%) articles reported engagement data. All primary analyses adopted treatment policy strategies, ignoring engagement levels. Only 19 (10.3%) articles provided additional intervention effect estimates accounting for user engagement: 2 (10.5%) conducted a complier-average-causal effect (CACE) analysis (principal stratum strategy) and 17 (89.5%) used a less-preferred per-protocol (PP) population excluding individuals failing to meet engagement criteria (estimand strategies unclear). Meta-analysis for PP estimates, when accounting for user engagement, changed the standardised effect to -0.18 95% CI (-0.32, -0.04) from − 0.14 95% CI (-0.24, -0.03) and sample sizes reduced by 33% decreasing precision, whereas meta-analysis for CACE estimates were − 0.19 95% CI (-0.42, 0.03) from − 0.16 95% CI (-0.38, 0.06) with no sample size decrease and less impact on precision. Discussio n Many articles report user engagement metrics but few assessed the impact on the intervention effect missing opportunities to answer important patient centred questions for how well DMHIs work for engaged users. Defining engagement in this area is complex, more research is needed to obtain ways to categorise this into groups. However, the majority that considered engagement in analysis used approaches most likely to induce bias.

Dan Ye,1 Ding Ding,1 Ling-Yun Pan,2 Qing Zhao,3 Long Chen,2 Min Zheng,1 Tong Zhang,1 Bing-Liang Ma1 1Department of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 3Department of Pharmacy, Jing’an District Zhabei Central Hospital, Shanghai, 200070, People’s Republic of ChinaCorrespondence: Bing-Liang Ma; Tong Zhang, Department of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, No. 1200 Cai Lun Road, Pudong New District, Shanghai, 201203, People’s Republic of China, Tel +86-021-5132 2199 ; +86-021-5132 2318, Fax +86-021-5132 2192, Email bingliang.ma@hotmail.com; zhangtongshutcm@hotmail.comPurpose: Docetaxel (DTX) is a valuable anti-tumor chemotherapy drug with limited oral bioavailability. This study aims to develop an effective oral delivery system for DTX using natural nanoparticles (Nnps) derived from Coptidis Rhizoma extract.Methods: DTX-loaded self-assembled nanoparticles (Nnps-DTX) were created using an optimized heat-induction strategy. Nnps-DTX’s shape, size, Zeta potential, and in vitro stability were all carefully examined. Additionally, the study investigated the encapsulation efficiency, loading capacity, crystal form, and intermolecular interactions of DTX in Nnps-DTX. Subsequently, the solubility, release, cellular uptake, metabolic stability, and preclinical pharmacokinetics of DTX in Nnps-DTX were systematically evaluated. Finally, the cytotoxicity of Nnps-DTX was assessed in three tumor cell lines.Results: Nnps-DTX was spherical in shape, 138.6 ± 8.2 nm in size, with a Zeta potential of − 20.8 ± 0.6 mV, a DTX encapsulation efficiency of 77.6 ± 8.5%, and a DTX loading capacity of 6.8 ± 1.9%. Hydrogen bonds, hydrophobic interactions, and electrostatic interactions were involved in the formation of Nnps-DTX. DTX within Nnps-DTX was in an amorphous form, resulting in enhanced solubility (23.3 times) and release compared to free DTX. Following oral treatment, the mice in the Nnps-DTX group had DTX peak concentrations 8.8, 23.4, 44.6, and 5.7 times higher in their portal vein, systemic circulation, liver, and lungs than the mice in the DTX group. Experiments performed in Caco-2 cells demonstrated a significant increase in DTX uptake by Nnps-DTX compared to free DTX, which was significantly inhibited by indomethacin, an inhibitor of caveolae-mediated endocytosis. Furthermore, compared to DTX, DTX in Nnps-DTX demonstrated better metabolic stability in liver microsomes. Notably, Nnps-DTX significantly reduced the viability of MCF-7, HCT116, and HepG2 cells.Conclusion: The novel self-assembled nanoparticles considerably enhanced the cellular absorption, solubility, release, metabolic stability, and pharmacokinetics of oral DTX and demonstrated strong cytotoxicity against tumor cell lines. Keywords: docetaxel, oral delivery, self-assembly, nanoparticles, pharmacokinetics, coptidis rhizoma

The emergence of multicancer early detection (MCED) tests holds promise for improving early cancer detection and public health outcomes. However, positive MCED test results require confirmation through recommended cancer diagnostic imaging modalities. To address these challenges, we have developed a consultation and work-up protocol for definitive diagnostic results post MCED testing, named SPOT-MAS. Developed through circulating tumor DNA (ctDNA) analysis and in line with professional guidelines and advisory board consensus, this protocol standardizes information to aid general practitioners in accessing, interpreting and managing SPOT-MAS results. Clinical effectiveness is demonstrated through a series of identified cancer cases. Our research indicates that the protocol could empower healthcare professionals to confidently interpret circulating tumor DNA test results for 5 common types of cancer, thereby facilitating the clinical integration of MCED tests.

BackgroundThe CIAO trial recently demonstrated a probable clinical benefit of omalizumab in the treatment of severe COVID-19; however, the mechanism underlying this benefit remains unclear. Therefore, we sought to longitudinally assess the impact of omalizumab on serum cytokines in CIAO trial patients to determine its mechanism of action.MethodsBlood samples were collected on days 0, 2, 7, and 14 from patients recruited into the CIAO trial and who consented to this substudy. Blood samples were tested by a panel of 25 inflammatory cytokines, as well as for markers of mast cell activation. Levels of inflammatory biomarkers were compared over time between omalizumab- and placebo-treated patients by generalized linear mixed-effects model. Associations between biomarkers and clinical outcomes were investigated by mixed-effects logistic regression.ResultsNineteen patients were recruited into this substudy; 10 were assigned to placebo and 9 to omalizumab. Monokine induced by gamma interferon was significantly positively associated with severe COVID-19 (Odds Ratio [OR] = 1.06, 95%CI = 1.00–1.11, p = 0.043). Further, omalizumab significantly reduced interleukin-15 (Coefficient = −0.95, p = 0.048) and macrophage inflammatory protein-1 (Coefficient = −1.31, p = 0.010) levels. However, neither was significant in analyses adjusting for multiple hypothesis testing.ConclusionAlthough limited by a small sample size, these results suggest that omalizumab’s potential benefit in COVID-19 may be mediated independently of modulation of the measured serum biomarkers. Further studies are needed to investigate omalizumab’s mechanism of action in COVID-19.

Sailesh Arulkumar,1 Elisa E Neuchat,2 Eric Ly,3 Austin Ingwei Ly,4 Kiana Fahimipour,5 Mehul J Desai6,7 1Department of Anesthesiology, SSM Health, St. Anthony’s Hospital, Oklahoma City, OK, USA; 2School of Medicine, Louisiana State University Health Sciences Center at Shreveport, Shreveport, LA, USA; 3Department of Anesthesiology, Brown University, Rhode Island Hospital, Providence, RI, USA; 4The University of Tennessee Health Science Center College of Medicine, Memphis, TN, USA; 5Department of Anesthesiology; Louisiana State University Health Sciences Center at New Orleans, New Orleans, LA, USA; 6International Spine Pain & Performance Center, Washington, DC, USA; 7George Washington University School of Medicine and Health Sciences, Washington, DC, USACorrespondence: Mehul J Desai, International Spine Pain and Performance Center, 2021 K Street NW Suite 615, Washington, DC, 20006, USA, Tel +1.202.808.8295, Fax +1.202.808.8296, Email drdesai@isppcenter.comAbstract: Scapulalgia or shoulder pain accounts for 16% of all musculoskeletal complaints in the healthy adult population and becomes more common as we age. When this pain exceeds 3 months in duration, it is deemed to be chronic, and typically treated in an escalating manner. Spanning a continuum of conservative and non-conservative measures, chronic shoulder pain treatments range from rest and physical therapy to surgery. Since each patient presents with a unique spectrum of symptoms a customized treatment plan is often required. Over the lifetime of many of these patients, a variety of treatment options are required. One of these treatment options, peripheral nerve stimulation (PNS), is a minimally invasive procedure in which an electrical impulse is delivered through a percutaneously implanted, small caliber electrode to a peripheral nerve proximal to the lesion which interferes with the pain signals. Over the past several years, significant growth of PNS in the treatment of chronic neuropathic pain has been observed. However, the procedural techniques have not been well described. The foundation of long-term, minimally invasive percutaneous PNS in patients with chronic shoulder pain, and procedural techniques for stimulating the suprascapular and axillary nerves using fluoroscopy or ultrasonography will be described in this report.Keywords: scapulalgia, shoulder pain, chronic pain, suprascapular nerve, axillary nerve, peripheral nerve stimulation

Jiang-Peng Cao,1– 3 Yuan-Hao Du,1,2,4 Lan-Yu Jia,5 Xiu-Mei Yin,1– 3 Li-Hong Yang,1,2 Lin-Ling Chen,6 Tao Jiang,1,2 Man Zhang,4 Tian Qiu1– 3 1Department of Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 2National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, People’s Republic of China; 3Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 4School of acupuncture & moxibustion and Tuina, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 5Department of Geriatric medicine, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, People’s Republic of China; 6Department of Traditional Chinese Medicine, Huzhou Central Hospital, Huzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Yuan-Hao Du, Email jpjs_cn@sina.comBackground: Cerebral blood flow and vascular structures serve as the fundamental components of brain metabolism and circulation. Acupuncture, an alternative and complementary medical approach, has demonstrated efficacy in treating cerebral ischemic stroke (CIS). Nevertheless, the mechanisms underlying the impact of acupuncture on vascular smooth muscle cell (VSMC) function remain uncertain. The objective of this systematic review and meta-analysis is to assess the alterations in VSMC function following acupuncture stimulation in CIS models.Methods: The databases PubMed, Web of Science, SCOPUS, and EMBASE were queried until November 2022 using a predetermined search strategy. The FORMAT BY SYRCLE guidelines were adhered to, and the risk of bias of the included studies was evaluated using the Risk of Bias tool developed by the Systematic Review Centre for Laboratory Animal Experimentation. The random-effects model was employed to estimate the standardized mean difference (SMD).Results: Eighteen articles are included in this review. Acupuncture showed significant positive effects on the region cerebral blood flow (SMD=8.15 [95% CI, 4.52 to 11.78]) and neurological deficiency (SMD=− 3.75 [95% CI, − 5.54 to − 1.97]). Descriptive analysis showed a probable mechanism of acupuncture stimulation in CIS rats related to VSMC function. Limitations and publication bias were presented in the studies.Conclusion: In this systematic review and meta-analysis, our findings indicate that acupuncture stimulation has the potential to improve regional cerebral blood flow and alleviate neurological deficits, possibly by regulating VSMC function. However, it is important to exercise caution when interpreting these results due to the limitations of animal experimental design and methodological quality.Keywords: acupuncture therapy, vascular smooth muscle cell, vasomotor, cerebral ischemic stroke, systematic review

Xin-Yu Liang,1,&ast; Li-yuan Mu,1,&ast; Lei Hu,2,&ast; Rui-ling She,1,&ast; Chen-yu Ma,1,&ast; Jun-han Feng,1,&ast; Zhi-yu Jiang,1 Zhao-xing Li,1 Xiu-quan Qu,1 Bai-qing Peng,1 Kai-nan Wu,1 Ling-quan Kong1 1Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Information Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling-quan Kong, Department of Breast and Thyroid Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China, Tel +8613101380893, Email huihuikp@163.comPurpose: Glycated hemoglobin (HbA1c) is widely used in diabetes management and now recommended for diagnosis and risk assessment. Our research focused on investigating the optimal cutoff points of HbA1c for diagnosis of diabetes and prediabetes in Chinese breast cancer women, aiming to enhance early detection and tailor treatment strategies.Patients and Methods: This study involved 309 breast cancer women without diabetes history in China. Patients were categorized into groups of newly diagnosed diabetes, prediabetes, and normal glucose tolerance using oral glucose tolerance test (OGTT) according to the 2010 ADA criteria. HbA1c data were collected from all patients. Receiver operating characteristic (ROC) curve analysis was used to assess the effectiveness of the HbA1c screening.Results: Among the 309 breast cancer women without diabetes history, 96 (31.0%) were identified with diabetes and 130 (42.1%) had prediabetes according to OGTT, and the incidence of normal glucose tolerance was only 26.9% (83). ROC curve analysis, using OGTT as a reference, revealed that the area under the curve of 0.903 (P< 0.001, 95% CI, 0.867– 0.938) for HbA1c alone, indicating high accuracy. The optimal HbA1c cutoff for identifying diabetes was determined to be 6.0%, with a sensitivity of 78.1% and specificity of 86.4%. For prediabetes, the ROC curve for HbA1c alone showed that the area under the ROC curve of 0.703 (P< 0.001, 95% CI, 0.632– 0.774), with an optimal cutoff of 5.5% (sensitivity of 76.9% and specificity of 51.8%).Conclusion: The prevalence of undiagnosed diabetes is very high in breast cancer women without diabetes history in China. The optimal cutoff points of HbA1c for identifying diabetes and prediabetes are 6.0% and 5.5% in Chinese breast cancer women, respectively.Keywords: breast cancer, diabetes, HbA1c, prediabetes

Lu Zhu,1,&ast; Jing Li,1,&ast; Zhao-Qin Wang,1,2,&ast; Yun-Jia Gu,1 Guo-Na Li,3 Wen-Jia Wang,1 Guang-Bin Pen,1 Qi Li,1 Meng-Die Wu,1 Hui-Rong Liu,1,2 Yan Huang,1,2 Lu-Yi Wu1 1Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Shanghai Research Institute of Acupuncture and Meridian, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3School of Acupuncture, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lu-Yi Wu, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, No. 110 Ganhe Road, Hongkou District, Shanghai City, 200437, People’s Republic of China, Email luyitcm@163.com Yan Huang, Shanghai Research Institute of Acupuncture and Meridian, Shanghai University of Traditional Chinese Medicine, No. 650 Wanping South Road, Xuhui District, Shanghai City, 200030, People’s Republic of China, Email huangyan@shutcm.edu.cnObjective: Moderate-to-severe pain is the most common clinical symptom in patients with hepatocellular carcinoma (HCC).This trial aimed to analyze the clinical efficacy of Transcutaneous electrical acupoint stimulation (TEAS) in patients of HCC with severe pain and provide a reliable reference for optimizing the clinical diagnostic and therapeutic strategies of HCC.Methods: A total of 104 eligible patients were randomly allocated to experimental and control groups in a ratio of 1:1.The treatment was administered for 1 week continuously. Patients in both groups were followed up 1 week after the end of the treatment.The primary outcome measure was the Numerical Rating Scale (NRS) score, whereas the secondary outcome measures included Brief Pain Inventory BPI-Q3, Q4, Q5 scores, analgesic dose, frequency of opioid-induced gastrointestinal side effects, Karnofsky Performance Status (KPS), Quality of Life Scale - Liver Cancer (QOL-LC), and Brief Fatigue Inventory (BFI) scores.Results: The NRS scores of experimental group was significantly lower after treatment and at the follow-up than baseline (average P< 0.01), there were also statistical differences between the groups at the above time points (average P< 0.01). BPI-Q3, -Q4, and -Q5 scores in the experimental group were decreased after treatment when compared with those before treatment (average P< 0.01). Furthermore, there were significant improvements of gastrointestinal side effects, KPS, QOL-LC and BPI in the experimental group after treatment, and the above results were statistically significant compared to the control group.Conclusion: 7-day TEAS treatment can significantly enhance the analgesic effect and maintain for the following week, also reduce the incidence of gastrointestinal side effects caused by opioids, and improve the quality of life of patients with moderate-to-severe HCC-related pain, which has reliable safety and certain clinical promotion value.Keywords: hepatocellular carcinoma pain, transcutaneous electrical acupoint stimulation, cancer pain, randomized controlled trial

Malarmugila Manimaran,1,&ast; Yin Yin Teo,2 James Chen Yong Kah,3 Adilet Beishenaliev,1 Yean Leng Loke,2 Yiing Yee Foo,1 Shiow-Fern Ng,4 Chin Fei Chee,5 Sek Peng Chin,6 Farid Nazer Faruqu,1 Chia-Yu Chang,7 Misni Misran,2 Lip Yong Chung,6 Bey Fen Leo,8,&ast; Shih-Hwa Chiou,9,10 Chia-Ching Chang,7,11– 13 Sun Tee Tay,14 Lik Voon Kiew1,7 1Department of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia; 2Department of Chemistry, Faculty of Science, Universiti Malaya, Kuala Lumpur, Malaysia; 3Department of Biomedical Engineering, College of Design and Engineering, National University of Singapore, Singapore, Singapore; 4Centre for Drug Delivery Technology and Vaccine, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia; 5Nanotechnology Catalysis Research Centre, Universiti Malaya, Kuala Lumpur, Malaysia; 6Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universiti Malaya, Kuala Lumpur, Malaysia; 7Department of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan, Republic of China; 8Department of Molecular Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia; 9Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China; 10Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei, Taiwan, Republic of China; 11Department of Electrophysics, National Yang Ming Chiao Tung University, Hsinchu, Taiwan, Republic of China; 12Center for Intelligent Drug Systems and Smart Bio-devices, National Yang Ming Chiao Tung University, Hsinchu, Taiwan, Republic of China; 13Institute of Physics, Academia Sinica, Nankang, Taipei, Taiwan, Republic of China; 14Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia&ast;These authors contributed equally to this workCorrespondence: Chia-Ching Chang; Lik Voon Kiew, Email ccchang01@nycu.edu.tw; lvkiew@um.edu.myIntroduction: Over 75% of clinical microbiological infections are caused by bacterial biofilms that grow on wounds or implantable medical devices. This work describes the development of a new poly(diallyldimethylammonium chloride) (PDADMAC)/alginate-coated gold nanorod (GNR/Alg/PDADMAC) that effectively disintegrates the biofilms of Staphylococcus aureus (S. aureus), a prominent pathogen responsible for hospital-acquired infections.Methods: GNR was synthesised via seed-mediated growth method, and the resulting nanoparticles were coated first with Alg and then PDADMAC. FTIR, zeta potential, transmission electron microscopy, and UV–Vis spectrophotometry analysis were performed to characterise the nanoparticles. The efficacy and speed of the non-coated GNR and GNR/Alg/PDADMAC in disintegrating S. aureus-preformed biofilms, as well as their in vitro biocompatibility (L929 murine fibroblast) were then studied.Results: The synthesised GNR/Alg/PDADMAC (mean length: 55.71 ± 1.15 nm, mean width: 23.70 ± 1.13 nm, aspect ratio: 2.35) was biocompatible and potent in eradicating preformed biofilms of methicillin-resistant (MRSA) and methicillin-susceptible S. aureus (MSSA) when compared to triclosan, an antiseptic used for disinfecting S. aureus colonisation on abiotic surfaces in the hospital. The minimum biofilm eradication concentrations of GNR/Alg/PDADMAC (MBEC50 for MRSA biofilm = 0.029 nM; MBEC50 for MSSA biofilm = 0.032 nM) were significantly lower than those of triclosan (MBEC50 for MRSA biofilm = 10,784 nM; MBEC50 for MRSA biofilm 5967 nM). Moreover, GNR/Alg/PDADMAC was effective in eradicating 50% of MRSA and MSSA biofilms within 17 min when used at a low concentration (0.15 nM), similar to triclosan at a much higher concentration (50 μM). Disintegration of MRSA and MSSA biofilms was confirmed by field emission scanning electron microscopy and confocal laser scanning microscopy.Conclusion: These findings support the potential application of GNR/Alg/PDADMAC as an alternative agent to conventional antiseptics and antibiotics for the eradication of medically important MRSA and MSSA biofilms.Keywords: biofilm, gold nanorod, S. aureus, PDADMAC, MRSA, MSSA

Agonists of the secretin receptor have potential applications for diseases of the cardiovascular, gastrointestinal, and metabolic systems, yet no clinically-active non-peptidyl agonists of this receptor have yet been developed. In the current work, we have identified a new small molecule lead compound with this pharmacological profile. We have prepared and characterized a systematic structure-activity series around this thiadiazole scaffold to better understand the molecular determinants of its activity. We were able to enhance the in vitro activity and to maintain the specificity of the parent compound. We found the most active candidate to be quite stable in plasma, although it was metabolized by hepatic microsomes. This chemical probe should be useful for in vitro studies and needs to be tested for in vivo pharmacological activity. This could be an important lead toward the development of a first-in-class orally active agonist of the secretin receptor, which could be useful for multiple disease states.

BackgroundClinical airway screening tests used to predict difficulties during airway management have low sensitivity and specificity. Point-of-care airway ultrasound has described measurements related to problems with difficult direct laryngoscopy. Nevertheless, the correlation between ultrasound parameters and videolaryngoscopy has not been published yet. The aim of this multicenter, prospective observational pilot study was to evaluate the applicability of clinical parameters and ultrasound measurements to find potential tracheal intubation difficulties when videolaryngoscopy is used.MethodsPreoperatively, six clinical airway assessments were performed: (1) modified Mallampati score, (2) thyromental distance, (3) sternomental distance, (4) interincisal distance, (5) upper lip bite test, and (6) neck circumference. Six ultrasound parameters were measured in awake patients: (1) distance from skin to hyoid bone, (2) distance from skin to epiglottis, (3) hyomental distance in neutral head position, (4) hyomental distance in head-extended position, (5) distance from skin to the deepest part of the palate, and (6) sagittal tongue area. And finally, there was one ultrasound measure obtained in anesthetized patients, the compressed sagittal tongue area during videolaryngoscopy. The difficulty for tracheal intubation using a McGrath™ Mac videolaryngoscope, the percentage of glottic opening, and Cormack-Lehane grade were also assessed.ResultsIn this cohort of 119 subjects, tongue dimensions, particularly the sagittal tongue area, showed a robust association with increased intubation difficulty using videolaryngoscopy. A multiparametric model combining the following three ultrasound variables in awake patients: (a) the distance from skin to epiglottis, (b) the distance from skin to the deepest part of the palate, and (c) the sagittal tongue area, yielded a sensitivity of 92.3%, specificity of 94.5%, positive predictive value of 82.8%, and negative predictive value of 97.8% (p

Lu-Yao Yang,1,&ast; Chao-Qing Li,1,2,&ast; Yu-Lin Zhang,1,2 Meng-Wen Ma,3 Wan Cheng,3 Guo-Jun Zhang1,2 1School of Laboratory Medicine, Hubei University of Chinese Medicine, Wuhan, 430065, People’s Republic of China; 2Hubei Shizhen Laboratory, Wuhan, 430065, People’s Republic of China; 3Britton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics - Hubei Bioinformatics & Molecular Imaging Key Laboratory, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guo-Jun Zhang, School of Laboratory Medicine, Hubei University of Chinese Medicine, Wuhan, People’s Republic of China, Email zhanggj@hbtcm.edu.cnAbstract: Extracellular vesicles can transmit intercellular information and transport biomolecules to recipient cells during various pathophysiological processes in the organism. Animal cell exosomes have been identified as potential nanodrugs delivery vehicles, yet they have some shortcomings such as high immunogenicity, high cytotoxicity, and complicated preparation procedures. In addition to exosomes, plant-derived extracellular vesicles (PDVs), which carry a variety of active substances, are another promising nano-transport vehicles emerging in recent years due to their stable physicochemical properties, wide source, and low cost. This work briefly introduces the collection and characterization of PDVs, then focuses on the application of PDVs as natural or engineered drug carriers in biomedicine, and finally discusses the development and challenges of PDVs in future applications.Keywords: plant-derived vesicles, activated biomaterials, nanodrugs delivery systems, biomedicine applications

Abstract Background Adolescence is a period of heightened vulnerability to developing mental health problems, and rates of mental health disorder in this age group have increased in the last decade. Preventing mental health problems developing before they become entrenched, particularly in adolescents who are at high risk, is an important research and clinical target. Here, we report the protocol for the trial of the ‘Building Resilience through Socioemotional Training’ (ReSET) intervention. ReSET is a new, preventative intervention that incorporates individual-based emotional training techniques and group-based social and communication skills training. We take a transdiagnostic approach, focusing on emotion processing and social mechanisms implicated in the onset and maintenance of various forms of psychopathology. Methods A cluster randomised allocation design is adopted with randomisation at the school year level. Five-hundred and forty adolescents (aged 12–14) will be randomised to either receive the intervention or not (passive control). The intervention is comprised of weekly sessions over an 8-week period, supplemented by two individual sessions. The primary outcomes, psychopathology symptoms and mental wellbeing, will be assessed pre- and post-intervention, and at a 1-year follow-up. Secondary outcomes are task-based assessments of emotion processing, social network data based on peer nominations, and subjective ratings of social relationships. These measures will be taken at baseline, post-intervention and 1-year follow-up. A subgroup of participants and stakeholders will be invited to take part in focus groups to assess the acceptability of the intervention. Discussion This project adopts a theory-based approach to the development of a new intervention designed to target the close connections between young people’s emotions and their interpersonal relationships. By embedding the intervention within a school setting and using a cluster-randomised design, we aim to develop and test a feasible, scalable intervention to prevent the onset of psychopathology in adolescence. Trial registration ISRCTN88585916. Trial registration date: 20/04/2023.

Minh Van Le,1,&ast; Tam Thai Thanh Tran,2,&ast; Loc Phu Huynh,3 Tho Kieu Anh Pham,2 Thi Van Vo,4 Hung Huynh Vinh Ly1 1Department of Neurology, Faculty of Medicine, Can Tho University of Medicine and Pharmacy, Can Tho, Vietnam; 2Department of Physiology, Faculty of Medicine, Can Tho University of Medicine and Pharmacy, Can Tho, Vietnam; 3Department of Neurology - Can Tho Central General Hospital, Can Tho, Vietnam; 4Department of Pediatrics, Faculty of Medicine, Can Tho University of Medicine and Pharmacy, Can Tho, Vietnam&ast;These authors contributed equally to this workCorrespondence: Hung Huynh Vinh Ly, Department of Neurology, Faculty of Medicine, Can Tho University of Medicine and Pharmacy, No. 179, Nguyen Van Cu Street, an Khanh Ward, Ninh Kieu District, Can Tho, 900000, Vietnam, Email 1853010822@student.ctump.edu.vnBackground: Cerebral venous thrombosis (CVT) is a challenging condition with potential long-term consequences, but it is also a treatable disorder that offers the possibility of complete recovery. This study was conducted to comprehensively investigate the clinical features, brain imaging findings, and treatment outcomes of patients diagnosed with cerebral venous thrombosis.Materials and Methods: Conducted as a cross-sectional descriptive study, patients diagnosed with cerebral venous thrombosis were enrolled at Can Tho Central General Hospital between January 2021 and June 2022.Results: Notably, a substantial proportion of patients (83.4%) exhibited signs of brain damage, with intracranial hemorrhage (50%), brain infarction (30.9%), subarachnoid hemorrhage (16.6%), and hemorrhagic infarct (4.7%) being the predominant findings. Thrombosis primarily affected the superior sagittal sinus (85.7%), transverse sinus (52.4%), and sigmoid sinus (42.8%). All patients received anticoagulation treatment, resulting in a favorable recovery upon hospital discharge for the majority (90.5%), while a small percentage (9.5%) experienced critical illness or death.Conclusion: Our study on cerebral venous thrombosis found diverse clinical presentations, primarily headache. Intracranial hemorrhage was common, affecting superior sagittal, transverse, and sigmoid sinuses. Most patients achieved favorable recoveries with anticoagulation treatment, emphasizing early intervention’s importance.The plain language summary: Cerebral venous thrombosis (CVT) is a less common condition when compared to arterial thrombosis, which has received more research attention. However, CVT has not received the same level of focus and investigation. The study aimed to comprehensively examine the clinical features, brain imaging findings, and treatment outcomes of patients diagnosed with CVT. The findings revealed that patients with CVT commonly presented with symptoms such as headache, limb weakness, seizures, vomiting, and consciousness disorders. Neuroimaging showed significant brain damage, including intracranial hemorrhage and brain infarction. However, with appropriate anticoagulation treatment, the majority of patients achieved favorable recoveries. The study emphasizes the importance of early intervention and highlights the need for improved diagnostic accuracy and treatment strategies for CVT.Keywords: cerebral venous thrombosis, CVT, hemorrhagic infarct, superior sagittal sinus

Yi-Jun Feng,1,&ast; Bing-Quan Wang,1,&ast; Lu-Lu Cao,2 Li-Ying Dong,3 Chu-Yi Zhang,1 Dong-Jian Hu,1 Zhen Zhou,3 Jin-Xiu Cao4 1Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, People’s Republic of China; 2Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 3Department of Encephalopathy and Acupuncture, Second Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300250, People’s Republic of China; 4Department of Geriatrics, Shanghai Eighth People’s Hospital, Shanghai, 200235, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhen Zhou, Department of Encephalopathy and Acupuncture, Second Teaching Hospital of Tianjin University of Traditional Chinese Medicine, No. 69 of Zengchan Road, Hebei District, Tianjin, 300250, People’s Republic of China, Tel +86-2260637106, Email zhouzhenzzzen@126.com Jin-Xiu Cao, Department of Geriatrics, Shanghai Eighth People’s Hospital, No. 8 Caobao Road, Xuhui District, Shanghai, 200235, People’s Republic of China, Tel +86-13502089031, Email caojinxui8f6@126.comObjective: This study was to investigate the mechanism of action and clinical efficacy of fire-needle therapy in improving neurological function in patients with acute cerebral infarction (identified as a wind-phlegm-blood stasis syndrome in traditional Chinese medicine).Methods: We included patients diagnosed with acute cerebral infarction (wind-phlegm-blood stasis syndrome) admitted to the Encephalopathy and Acupuncture Center of the Second Affiliated Hospital of Tianjin University of Chinese Medicine. We randomly allocated them into the treatment and control groups, with 45 cases in each group. Acupuncture treatments that focused on regulating the mind and dredging the collaterals were used in the control group, while the treatment group additionally received fire-needle therapy. Our indicators included the National Institutes of Health Stroke Scale (NIHSS) scores, the Fugl-Meyer Assessment (FMA) scale, peripheral blood tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17), hypersensitivity C-reactive protein (hs-CRP), and intestinal metabolites short-chain fatty acids (SCFAs). We measured these indicators before treatment and 14 days after treatment.Results: The post-treatment NIHSS scores of the two groups were significantly reduced (P < 0.05), and the treatment group showed a more significant decline in the score when compared to the control group (P < 0.05). The treatment group showing significant improvement in the domains of reflex activity, mobility, cooperative movement, and finger movement (P < 0.05). Both groups showed a significant decrease in the IL-17 and hs-CRP levels (P < 0.05), with the treatment group demonstrating a significant declining trend when compared to the control group (P < 0.05). The levels of acetic acid, propionic acid, butyric acid, and valeric acid all increased significantly in the two groups (P < 0.05), with acetic acid and butyric acid increasing significantly in the treatment group when compared to the control group (P < 0.05). Clinical efficacy rate: 78.6% of patients in the treatment group had an excellent rate, whereas it was 30.0% in the control group, and the difference was statistically significant (P < 0.001).Conclusion: Fire-needle therapy was effective in upregulating the SCFA content in patients with acute cerebral infarction (wind-phlegm-blood stasis syndrome), inhibiting the level of the inflammatory response, and improving the recovery of neurological functions.Clinical registration number: Registration website link: https://www.chictr.org.cn. Registration date: 2022/9/27. Registration number: ChiCTR2200064122.Keywords: acute cerebral infarction, fire-needle therapy, short-chain fatty acids, wind-phlegm-blood stasis syndrome

Abstract Background Healthcare system data (HSD) are increasingly used in clinical trials, augmenting or replacing traditional methods of collecting outcome data. This study, PRIMORANT, set out to identify, in the UK context, issues to be considered before the decision to use HSD for outcome data in a clinical trial is finalised, a methodological question prioritised by the clinical trials community. Methods The PRIMORANT study had three phases. First, an initial workshop was held to scope the issues faced by trialists when considering whether to use HSDs for trial outcomes. Second, a consultation exercise was undertaken with clinical trials unit (CTU) staff, trialists, methodologists, clinicians, funding panels and data providers. Third, a final discussion workshop was held, at which the results of the consultation were fed back, case studies presented, and issues considered in small breakout groups. Results Key topics included in the consultation process were the validity of outcome data, timeliness of data capture, internal pilots, data-sharing, practical issues, and decision-making. A majority of consultation respondents (n = 78, 95%) considered the development of guidance for trialists to be feasible. Guidance was developed following the discussion workshop, for the five broad areas of terminology, feasibility, internal pilots, onward data sharing, and data archiving. Conclusions We provide guidance to inform decisions about whether or not to use HSDs for outcomes, and if so, to assist trialists in working with registries and other HSD providers to improve the design and delivery of trials.

Abstract Background The purpose of this 6-month intervention pilot feasibility randomised trial was to test sending brief messages using mobile phones to promote self-management through taking medication as prescribed to people with type 2 diabetes. This was to inform the design and conduct of a future large-scale United Kingdom-based clinical trial and establish the feasibility of recruitment, the technology used, follow-up, and data collection. Methods A multicentre individually randomised, controlled parallel group trial in primary care, recruiting adults (≥ 35 years) with type 2 diabetes in England. Consenting participants were randomly allocated to receive short message system text messages up to four times a week, or usual care, for a period of 6 months; messages contained behavioural change techniques targeting medication use. The primary outcome was the rate of recruitment to randomisation of participants to the trial with a planned rate of 22 participants randomised per month. The study also aimed to establish the feasibility of follow-up at 6 months, with an aim of retaining more than 80% of participants. Data, including patient-reported measures, were collected at baseline and the end of the 6-month follow-up period, and a notes review was completed at 24 months. Results The trial took place between 26 November 2018 and 30 September 2019. In total 209 participants were randomly allocated to intervention (n = 103) or usual care (n = 106). The maximum rate of monthly recruitment to the trial was 60–80 participants per month. In total, 12,734 messages were sent to participants. Of these messages, 47 were identified as having failed to be sent by the service provider. Participants sent 2,864 messages to the automated messaging system. Baseline data from medical records were available for > 90% of participants with the exception of cholesterol (78.9%). At 6 months, a further HbA1c measurement was reported for 67% of participants. In total medical record data were available at 6 months for 207 (99.0%) of participants and completed self-report data were available for 177 (84.7%) of participants. Conclusion The feasibility of a large-scale randomised evaluation of brief message intervention for people with type 2 diabetes appears to be high using this efficient design. Failure rate of sending messages is low, rapid recruitment was achieved among people with type 2 diabetes, clinical data is available on participants from routine medical records and self-report of economic measures was acceptable. Trial registration ISCTRN ISRCTN13404264. Registered on 10 October 2018.

Ling-Yun Bao,&ast; Xin-Yue Dao,&ast; Kun Du Department of Neonate, Kun Ming Children’s Hospital, Yunnan, 650021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kun Du, Department of Neonate, Kun Ming Children’s Hospital, No. 28 of Shulin Road, Yunnan, 650021, People’s Republic of China, Tel +86 15388843393, Email kdidljtdr_09@outlook.comAbstract: Neonatal respiratory distress syndrome (NRDS) is a common critical disease in neonates. Early diagnosis and timely treatment are crucial. Historically, X-ray imaging was the primary method for diagnosing NRDS. However, this method carries radiation exposure risks, making it unsuitable for dynamic lung condition monitoring. In addition, neonates who are critically ill require bedside imaging, but diagnostic delays are often unavoidable due to equipment transportation and positioning limitations. These challenges have been resolved with the introduction of lung ultrasound (LUS) in neonatal intensive care. The diagnostic efficacy and specificity of LUS for NRDS is superior to that of X-ray. The non-invasive, dynamic, and real-time benefits of LUS also allow for real-time monitoring of lung changes throughout treatment for NRDS, yielding important insights for guiding therapy. In this paper, we examine the ultrasonographic characteristics of NRDS and the recent progress in the application of ultrasound in the diagnosis and treatment of NRDS while aiming to promote wider adoption of this method.Keywords: dynamic monitoring, lung ultrasound, neonates, respiratory distress syndrome, NRDS, point of care ultrasound

Yan Liu, Song Yuan, Li-Yi Wang, Si Chen, Yang Li, Wei Ma Department of Infection Control, The Second Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of ChinaCorrespondence: Wei Ma, Department of Infection Control, The Second Hospital of Hebei Medical University, No. 215 of Heping West Road, Shijiazhuang, 050000, People’s Republic of China, Tel +86-18603297270, Fax +86 (311) 66007439, Email maweimmw6@126.comObjective: The objective of this study is to examine the qualification rate of hand disinfection in the surgical department wards and analyze the influencing factors.Methods: A surprise assessment was carried out to evaluate the daily adherence to hand hygiene protocols in the surgical department wards. We aimed to investigate the factors that impact the qualification rate of hand disinfection.Results: In this study, the qualification rate of hand disinfection was determined to be 64.38%. Notably, this rate exhibited significant variations based on gender, age, surgical site, and department category. Specifically, the qualification rate of hand disinfection among female participants stood at 82.35%, surpassing the qualification rate observed among male counterparts of 52.83%. Furthermore, doctors in the age group of 41– 50 years demonstrated the highest qualification rate, and the abdominal surgical site exhibited the most noteworthy qualification rate, reaching 79.49%. The outcomes of the multiple logistic regression analysis highlighted the significance of age and gender as influential factors impacting the qualification rate. Specifically, doctors aged 51 years or older exhibited the lowest hand hygiene compliance, whereas female doctors demonstrated a notably higher qualification rate compared to their male counterparts.Conclusion: The disheartening qualification rate of hand disinfection highlights a concerning lack of awareness regarding hand hygiene among surgeons in their professional duties. Consequently, targeted interventions are imperative, focusing on intensified training, educational initiatives, enhanced supervision, and internal performance evaluations for key groups. The findings not only serve as a valuable database but also offer a viable roadmap for similar hospitals to reinforce the management of nosocomial infections.Keywords: hand hygiene, hand disinfection, influencing factors, qualification rate, surgeons

Li-Yan Sun,1 Qiong Yu,2 Cai-Ming He,2 Song-Xing Wang3 1Institution of Transfusion Medicine, Shenzhen Blood Center, Shenzhen, People’s Republic of China; 2Quality Control Department, Shenzhen Blood Center, Shenzhen, People’s Republic of China; 3Business Management Department, Shenzhen Blood Center, Shenzhen, People’s Republic of ChinaCorrespondence: Song-Xing Wang, Email wsxdxyx2003@163.comBackground: The adverse donor reaction (ADR) means the uncomfortable feeling felt by blood donors during the whole process of blood donation, which can affect the blood donation behavior of blood donors. So, it is very necessary for blood centers to monitor and prevent it.Methods: Data about ADRs in Shenzhen Blood Center from January 2018 to December 2022 were collected, and correlation analysis was conducted using SPSS 24.0 software.Results: From January 2018 to December 2022, a total of 1265 ADRs occurred in 642,767 blood donations in Shenzhen Blood Center, with an incidence of 0.20%. Most of the ADRs were mild and occurred during blood collections (> 90%). The ADR rate of young individuals aged 18– 29 years old was the highest (p< 0.0001). In addition, a higher ADR rate was observed in first-time blood donors, whole blood donors, and blood donors who donated in the mobile sites (p< 0.05).Conclusion: The occurrence of ADRs is related to the sociodemographic factors of blood donors, including age, donation type, donation history, and donation sites. Shenzhen Blood Centers should pay special attention to the process of blood donation among young blood donors aged 18– 29 years old, first-time blood donors, whole-blood donors, and blood donors who donate at mobile sites to further reduce the occurrence of ADRs.Keywords: blood donors, adverse donor reactions, sociodemographic factors

Zi-Hao Li,1,&ast; Jia-Yi Li,2,&ast; Yong-Jie Zhu,1,3,&ast; Lei Dai,3,&ast; Zuo-Tao Wu,3 Ju-Sen Nong,4 Ting Zhuo,5 Fu-Li Li,1 Ling-Yun He,1 Hong-Hua Liang,1 Feng-Ling Zang,1 Yong-Yong Wang,3 Ming-Wu Chen,3 Wei-Jia Huang,1 Jian-Bin Cao1 1Department of Thoracic Surgery, Liuzhou People’s Hospital Affiliated to Guangxi Medical University, Liuzhou, Guangxi, People’s Republic of China; 2Department of Nephrology, Liuzhou People’s Hospital Affiliated to Guangxi Medical University, Liuzhou, Guangxi, People’s Republic of China; 3Department of Cardio-Thoracic Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 4Department of Pediatric Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 5Department of Respiratory Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei-Jia Huang; Jian-Bin Cao, Email huangbolin62@126.com; 18907722555@163.comBackground: Lung adenocarcinoma (LUAD) has high morbidity and mortality. Current studies indicate nucleoporin 107 (NUP107) is involved in the construction of nuclear pore complex, and NUP107 overexpression contributes to the growth and development in most types of cancers, but its effect in LUAD has not been elucidated.Methods: Differences in NUP107 expression were investigated using the Cancer Genome Atlas (TCGA) and multiple Gene Expression Omnibus (GEO) data sets. Enrichment analysis were implemented to probe the NUP107 function. The association of NUP107 with the degree of immune cell infiltration was investigated by the TIMER database, single-sample gene set enrichment analysis (ssGSEA), and ESTIMATE. The association of NUP107 expression with tumor mutation burden (TMB), TP53, and immune checkpoint was analyzed. Single-cell RNA sequencing data were used to detect NUP107 expression in different cell clusters. Finally, we performed real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) to prove the difference of NUP107 expression.Results: NUP107 was overexpressed in LUAD and mainly expressed in cancer stem cell (CSC). Overexpression of NUP107 in LUAD suggested a poorer prognosis. Functional enrichment analysis pointed out that NUP107 was mainly linked to the regulation of cell cycle. Both immune cell infiltration and TMB were found to be in connection with NUP107. Cases in the group with high NUP107 expression had poorer immune infiltration, but had higher expression of immune checkpoints, TMB, and proportion of TP53 mutations.Conclusion: NUP107 is a sensitive diagnostic and prognostic factor for LUAD and may be involved in tumor progression through its effects on cell cycle and immune infiltration.Keywords: lung adenocarcinoma, nucleoporin 107, immune infiltration, tumor mutation burden, TP53, immune checkpoint

Abstract Background The COVID-19 pandemic has made devastating impacts on public health and global economy. While most people experience mild symptoms, it is highly transmissible and deadly in at-risk populations. Telemedicine has the potential to prevent hospitalization and provide remote care. Methods This retrospective study included 336 people with COVID-19, among which 141 (42%) and 195 (58%) were in Delta and Omicron dominant groups, respectively. Patients were confirmed to have COVID-19 by PCR or rapid test and were cared for via telemedicine. Severe cases were hospitalized for more intensive treatment. Results The majority of individuals recovered at home (97.02%), while 2.98% required hospitalization. All hospital admissions were in Delta dominant group. No deaths were reported. Delta dominant group was more likely to develop loss of taste and smell, decreased appetite and need longer treatment time than those in Omicron dominant group. Conclusions Telemedicine is a safe measure to provide at-home care for people with COVID-19 infections caused by both Delta and Omicron variants. Trial registration This study was approved by the Institutional Review Board Committee of University of Medicine and Pharmacy at Ho Chi Minh City (IRB No: 22115–DHYD).

Jia-Rui Du, Deng-Ke Teng, Yang Wang, Qimeihui Wang, Yuan-Qiang Lin, Qiang Luo, Jia-Nan Xue, Ling-Yu Zhu, Peng Dong, Gen-Mao Zhang, Yan Liu, Zhi-Xia Sun, Hui Wang,&ast; Guo-Qing Sui&ast; Department of Ultrasound, China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Wang; Guo-Qing Sui, Email whui66@jlu.edu.cn; suiguoqing@jlu.edu.cnPurpose: Sonodynamic therapy (SDT), with its high tissue penetration and noninvasive advantages, represents an emerging approach to eradicating solid tumors. However, the outcomes of SDT are typically hampered by the low oxygen content and immunosuppression in the tumor microenvironment (TME). Accordingly, we constructed a cascade nanoplatform to regulate the TME and improve the anti-tumor efficiency of SDT.Methods: In this study, we rationally design cascade nanoplatform by incorporating immunostimulant hyaluronic acid (HA) and sonosensitizer chlorin e6 (Ce6) on the polydopamine nanocarrier that is pre-doped with platinum nanozymes (designated Ce6/Pt@PDA-HA, PPCH).Results: The cascade reactions of PPCH are evidenced by the results that HA exhibits reversing immunosuppressive that converts M2 macrophages into M1 macrophages in situ, while producing H2O2, and then platinum nanozymes further catalyze the H2O2 to produce O2, and O2 produces abundant singlet oxygen (1O2) under the action of Ce6 and low-intensity focused ultrasound (LIFU), resulting in a domino effect and further amplifying the efficacy of SDT. Due to its pH responsiveness and mitochondrial targeting, PPCH effectively accumulates in tumor cells. Under LIFU irradiation, PPCH effectively reverses immunosuppression, alleviates hypoxia in the TME, enhances reactive oxygen species (ROS) generation, and enhances SDT efficacy for eliminating tumor cells in vivo and in vitro. Meanwhile, an in vivo dual-modal imaging including fluorescence and photoacoustic imaging achieves precise tumor diagnosis.Conclusion: This cascade nanoplatform will provide a promising strategy for enhancing SDT eradication against tumors by modulating immunosuppression and relieving hypoxia.Keywords: tumor microenvironment, tumor-associated macrophages, cascade reactions, sonodynamic therapy, tumor hypoxia

Key clinical message In in vitro fertilization (IVF), laser offers several advantages. In this study, we employed laser to eliminate the zona pellucida of a contaminated embryo. This approach helps to rescue embryo with bacterial contamination, and improve embryo‐endometrium interaction. Abstract To present a case report on the removal of a contaminated zona pellucida from an embryo of patient with a history of recurrent implantation failure (RIF), which was followed by a successful live birth. We present the case of a 34‐year‐old patient with a history of 3 years of infertility who underwent in vitro fertilization. During the culture process, the embryos became contaminated, leading to three failed implantations. Despite the aneuploidy of the embryo and the implementation of a washing technique, the contamination persisted. In the final attempt, the contaminated zona pellucida was successfully removed using laser, followed by embryo transfer, resulting in a live birth. We provided detailed clinical information, including patient demographics, infertility history, ovarian response, evidence of bacterial contamination, embryo development, treatment protocols, and outcomes. Laser excision of the zona pellucida is a safe and effective method for addressing bacterial infection in embryos.

BackgroundOver the last few years, ultrasonography has been introduced as the fifth pillar to patient’s bedside physical examination. Clinical assessments aim to screen and look for airway difficulties to predict difficult intubations, but none have demonstrated a significant predictive capacity. Recent systematic reviews have established a correlation between ultrasound imaging and difficult direct laryngoscopy. The primary objective of this study was to determine whether the utilization of ultrasonography to examine the upper airway could accurately predict difficult direct laryngoscopy.MethodsThis is a prospective observational study including 102 adult patients that required general anesthesia for elective surgery. Preoperatively, clinical airway assessments were performed. Data such as Mallampati-Samsoon grade (MS), upper lip bite test (ULBT), thyromental (TMD) and sternomental distance (SMD), cervical circumference (CC) and the Arné risk index were collected. Ultrasound evaluation was taken at five different levels in two planes, parasagittal and transverse. Therefore, the following measurements were registered: distance from skin to hyoid bone (DSHB), distance from skin to thyrohyoid membrane (DSTHM), distance from skin to epiglottis (DSE), distance from skin to thyroid cartilage (DSTC) and distance from hyoid bone and thyroid cartilage (DHBTC). Patients were divided into two groups based on the difficulty to perform direct laryngoscopy, according to Cormack-Lehane (C-L) classification. Grades I and II were classified as easy laryngoscopy and grades III or IV as difficult. Logistic regression models and the Receiver Operating Characteristic (ROC) curve was employed to determine the diagnostic precision of ultrasound measurements to distinguish difficult laryngoscopy (DL).ResultsThe following risk score for DL was obtained, DSTHM ≥ 1.60 cm (2 points), DSTC ≥ 0.78 cm (3 points) and gender (2 points for males). The score can range from 0 to 7 points, and showed and AUC (95% CI) of 0.84 (0.74–0.95). A score of 5 points or higher indicates a 34-fold increase in the risk of finding DL (p = 0.0010), sensitivity of 91.67, specificity of 75.56, positive predictive value of 33.33, and negative predictive value of 98.55.ConclusionThe use of ultrasonography combined with classic clinical screening tests are useful tools to predict difficult direct laryngoscopy.

Background: In 2018, GOLD addressed the issues of genotypes associated with risk factors for COPD. The genome-wide association study (GWAS) demonstrated an association between COPD and several genetic variants of single nucleotide polymorphisms (SNPs) of the FAM13A gene with the risk of COPD. Objective: To study the single nucleotide polymorphisms rs2869967 and rs17014601 of the FAM13A gene in chronic obstructive pulmonary disease. Subjects and research methods: 80 subjects diagnosed with COPD and 80 subjects determined not to have COPD according to GOLD 2020 criteria; the subjects were clinically examined, interviewed, and identified as possessing single nucleotide polymorphisms using the sanger sequencing method on whole blood samples. Results: The male/female ratio of the patient group and the control group was 79/1 and 39/1, respectively. The percentages of C and T alleles of rs2869967 in COPD patients were 50.6% and 49.4%, respectively. The percentages of C and T alleles of rs17014601 in COPD patients were 31.9% and 68.1%, respectively. At rs17014601, the ratio values of alleles T and C in the disease group and the control group were markedly different, making them statistically reliable (p = 0.031). The rate of CT genotype in the group of patients was considerably higher than that of the control group. The TT homozygous genotype had a lower risk of COPD compared with the other genotypes in the dominant model (ORTT/(CC + CT) = 0.441; CI95% = 0.233–0.833); this difference was statistically significant (p = 0.012). Conclusions: With rs17014601, it is characteristic that the frequency of the T allele appears more than the C allele, and the CT heterozygous phenotype accounts for the highest proportion in rs17014601 and rs2869967 recorded in COPD patients. There is an association between the genetic variant of the SNP FAM13A-rs17014601 and the risk of COPD.

Abstract Background The evidence for the clinical utility of pharmacogenomic (PGx) testing is growing, and guidelines exist for the use of PGx testing to inform prescribing of 13 antidepressants. Although previous randomised controlled trials of PGx testing for antidepressant prescribing have shown an association with remission of depression in clinical psychiatric settings, few trials have focused on the primary care setting, where most antidepressant prescribing occurs. Methods The PRESIDE Trial is a stratified double-blinded randomised controlled superiority trial that aims to evaluate the impact of a PGx-informed antidepressant prescribing report (compared with standard prescribing using the Australian Therapeutic Guidelines) on depressive symptoms after 12 weeks, when delivered in primary care. Six hundred seventy-two patients aged 18–65 years of general practitioners (GPs) in Victoria with moderate to severe depressive symptoms, measured using the Patient Health Questionnaire-9 (PHQ-9), will be randomly allocated 1:1 to each arm using a computer-generated sequence. Participants and GPs will be blinded to the study arm. The primary outcome is a difference between arms in the change of depressive symptoms, measured using the PHQ-9 after 12 weeks. Secondary outcomes include a difference between the arms in change in PHQ-9 score at 4, 8 and 26 weeks, proportion in remission at 12 weeks, a change in side effect profile of antidepressant medications, adherence to antidepressant medications, change in quality of life and cost-effectiveness of the intervention. Discussion This trial will provide evidence as to whether PGx-informed antidepressant prescribing is clinically efficacious and cost-effective. It will inform national and international policy and guidelines about the use of PGx to select antidepressants for people with moderate to severe depressive symptoms presenting in primary care. Trial registration Australian and New Zealand Clinical Trial Registry ACTRN12621000181808. Registered on 22 February 2021.

AbstractBackground Early in the COVID-19 pandemic, GPs had to distinguish SARS-CoV-2 from other aetiologies in patients presenting with respiratory tract infection (RTI) symptoms on clinical grounds and adapt management accordingly.Objectives To test the diagnostic accuracy of GPs’ clinical diagnosis of a SARS-CoV-2 infection in a period when COVID-19 was a new disease. To describe GPs’ management of patients presenting with RTI for whom no confirmed diagnosis was available. To investigate associations between patient and clinical features with a SARS-CoV-2 infection.Methods In April 2020–March 2021, 876 patients (9 countries) were recruited when they contacted their GP with symptoms of an RTI of unknown aetiology. A swab was taken at baseline for later analysis. Aetiology (PCR), diagnostic accuracy of GPs’ clinical SARS-CoV-2 diagnosis, and patient management were explored. Factors related to SARS-CoV-2 infection were determined by logistic regression modelling.Results GPs suspected SARS-CoV-2 in 53% of patients whereas 27% of patients tested positive for SARS-CoV-2. True-positive patients (23%) were more intensively managed for follow-up, antiviral prescribing and advice than true-negatives (42%). False negatives (5%) were under-advised, particularly for social distancing and isolation. Older age (OR: 1.02 (1.01–1.03)), male sex (OR: 1.68 (1.16–2.41)), loss of taste/smell (OR: 5.8 (3.7–9)), fever (OR: 1.9 (1.3–2.8)), muscle aches (OR: 2.1 (1.5–3)), and a known risk factor for COVID-19 (travel, health care worker, contact with proven case; OR: 2.7 (1.8–4)) were predictive of SARS-CoV-2 infection. Absence of loss of taste/smell, fever, muscle aches and a known risk factor for COVID-19 correctly excluded SARS-CoV-2 in 92.3% of patients, whereas presence of 3, or 4 of these variables correctly classified SARS-CoV-2 in 57.7% and 87.1%.Conclusion Correct clinical diagnosis of SARS-CoV-2 infection, without POC-testing available, appeared to be complicated.

Yan-Bin Liu,1 Li-Juan Zuo,2 Ya-Chao Liu,1 Yan-Ping Li,1 Yun-Chao Xin,1 Hong-Yan Zhang,3 Li-Yuan Hou4 1Department of ENT & HN Surgery, The First Affiliated Hospital of Hebei North University, Zhangjiakou City, Hebei, 075000, People’s Republic of China; 2Department of Endocrine, The First Affiliated Hospital of Hebei North University, Zhangjiakou City, Hebei, 075000, People’s Republic of China; 3Departmentof Psychiatry, The First Affiliated Hospital of Hebei North University, Zhangjiakou City, Hebei, 075000, People’s Republic of China; 4Department of Nuclear Medicine, The First Affiliated Hospital of Hebei North University, Zhangjiakou City, Hebei, 075000, People’s Republic of ChinaCorrespondence: Yan-Bin Liu, Department of ENT & HN Surgery, The First Affiliated Hospital of Hebei North University, No. 12, Changqing Street, Qiaoxi District, Zhangjiakou, Hebei, 075000, People’s Republic of China, Email liuyanbin19830524@163.comObjective: This study aimed to design a standard method of psychological intervention and evaluate the effect of such psychological intervention against the psychological distress of differentiated thyroid cancer (DTC) patients in the treatment with radioactive iodine.Methods: The enrolled patients were randomly divided into the intervention group and the control group. Both the patients in the 2 groups received the routine nursing care, while the patients in the intervention group also received the additional standard psychological interventions. The questionnaires including patient health questionnaire-9 (PHQ-9), generalized anxiety disorder 7-item (GAD-7), cancer fatigue scale (CFS) and positive and negative affect schedule (PANAS) were used to assess psychological status. These questionnaires were performed at week 0 (T0), week 8 (T1, immediately after the last time of intervention) and week 24 (T2, 16 weeks after the intervention).Results: PHQ-9, GAD-7, CFS and Negative Affect (NA) scores measured at T1 and T2 in the intervention group were significantly lower than those in the control group (P < 0.001). And intervention group also had higher positive affect (PA) scores at T1 and T2 (P < 0.001). Furthermore, the changes of PHQ-9, GAD-7, CFS, PA and NA scores from T0 to T1 and T0 to T2 were more evident in the intervention group than in the control group.Conclusion: Psychological intervention could significantly improve psychological distress of DTC patients in the treatment with radioactive iodine.Keywords: differentiated thyroid cancer, radioactive iodine, psychological intervention, psychological distress, mood

Song-Xing Wang,&ast; Li-Yan Sun,&ast; Qiong Yu, Tong Li, Ran Li, Yun-Ping Xu, Jin-Feng Zeng Shenzhen Blood Center, Shenzhen, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yun-Ping Xu; Jin-Feng Zeng, Email yunpingxu1982@qq.com; zzengjf@163.comBackground: New HIV (Human immune deficiency virus) infections are continuously increasing in China and it remains a huge challenge to blood donation. As access to health services has affected by COVID-19 (Corona virus disease 2019) pandemic, a drop in new diagnoses (especially HIV) was observed worldwide.Methods: During 2013– 2021, 735,247 specimens from unpaid blood donors collected by Shenzhen Blood Center underwent ELISA (Enzyme -linked immunosorbent assay) and NAT (Nucleic acid test). Samples with reactivity results were sent to the Shenzhen Center for Disease Control and Prevention for WB (Western blot). All data were statistically analyzed by the Chi-Square test.Results: From 2013 to 2021, the prevalence of HIV among male blood donors was higher than in females (P < 0.01). During the COVID-19 pandemic, the prevalence of HIV among repeat blood donors decreased significantly compared to 2019 (P < 0.05), and the characteristics of blood donors changed in 2020 compared to 2019 and 2021.Conclusion: The high proportion of female blood donors would help prevent HIV from getting into the blood supply. The COVID-19 pandemic affected the demographics of blood donors as well as the prevalence of HIV among repeat blood donors. An increased number of repeat blood donors can help decrease the risk of HIV transfusion transmission during the epidemic.Keywords: COVID-19, Shenzhen, blood donors, HIV

Kang-Da Zhang,1 Lin-Yu Wang,1 Zhi-Hua Zhang,1 Dan-Xu Zhang,1 Xiao-Wen Lin,2 Tao Meng,1 Feng Qi1 1Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, People’s Republic of China; 2Department of Pain Management, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of ChinaCorrespondence: Tao Meng; Feng Qi, Department of Anesthesiology, Qilu Hospital of Shandong University, No.107 Wenhua Xilu, Jinan, Shandong, 250012, People’s Republic of China, Email mengtao@sdu.edu.cn; 198962001111@sdu.edu.cnObjective: Several guidelines highlight the beneficial impact of exercise on the management of symptoms and health-related quality of life (HRQOL) in patients with fibromyalgia syndrome (FMS). However, few analyses have compared different types of exercise. We, therefore, intent to compare the effects of different exercise types on improving the overall HRQOL and typical symptoms in patients with FMS.Methods: Medline, Embase, the Cochrane Register of Clinical Trials, and NIH ClinicalTrials.gov were searched from inception to April 21, 2022. Randomized clinical trials (RCTs) were included to assess the impact of exercise intervention on health parameters in adult FMS patients. Data were extracted independently and a frequentist network meta-analyses (NMA) was performed to rank the effects of interventions according to P-scores. The NMA evidence certainty was assessed using the method recommended by Grading of Recommendations Assessment, Development, and Evaluation Working Group.Results: A total of 57 RCTs were identified, including 3319 participants, involving 9 interventions (7 types of exercise, 2 controls). Of all treatments compared with usual care in efficacy outcomes, Mind-body exercise was associated with the best HRQOL (SMD, − 12.12; 95% CI, − 15.79 to − 8.45). On the other characteristic symptom dimensions, based on moderate quality evidence, sensorimotor training was associated with minimal pain scores compared with usual care (SMD, − 1.81; 95% CI, − 2.81 to − 0.82), whole body vibration therapy was most promising for improving sleep quality (SMD, − 6.95; 95% CI, − 10.03 to − 3.87), pool-based aerobic exercise was most likely to ease anxiety (SMD, − 4.83; 95% CI, − 7.47 to − 2.19), and whole body vibration was most likely to improve depression (SMD, − 10.44; 95% CI, − 22.00 to 1.12).Conclusion: Mind-body exercise seems to be the most effective exercise to improve the overall HRQOL of patients with FMS. But at the same time, clinicians still need to develop individualized exercise plans for patients according to their symptoms and accessibility.Keywords: fibromyalgia syndrome, exercise, quality of life, systematic review, network meta-analysis

Jia-Li Shen, Ling-Yan Hang, Fan He, Xiao Xu, Hui-Ping Sun Department of Orthopaedic, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, People’s Republic of ChinaCorrespondence: Jia-Li Shen, Department of Orthopaedic, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, No. 261 Huansha Road, Shangcheng District, Hangzhou, 310006, People’s Republic of China, Email 13857169118@163.comObjective: To investigate the application value of the interventional treatment model for improving the recovery of elderly patients after total hip arthroplasty (THA).Methods: A total of 50 patients who received THA were randomly divided into the control group (25 cases) undergoing traditional treatment and the experimental group (25 cases) undergoing intervention of cognition, emotion, environment, education, nutrition, and sleep. The mini-mental state examination (MMSE) score, the incidence and duration of postoperative cognitive dysfunction (POCD), the out-of-bed activity time, hospital stays, and the satisfaction degree of patients were compared between the two groups.Results: There was no statistically significant difference in basic information between the two groups. On days 7 and 14 after surgery, the MMSE score of the control group was significantly lower than that of the experimental group (P < 0.05). The incidence of POCD in the experimental group was lower and its duration was shorter than in the control group but without statistical significance. Besides, the significantly decreased out-of-bed activity time, the reduced length of hospital stay, and the higher satisfaction degree were observed in the experimental group (P < 0.05).Conclusion: Interventional treatment model could significantly increase the MMSE score, accelerate the recovery of elderly patients after THA, and increase their satisfaction degree.Keywords: interventional treatment model, postoperative cognitive dysfunction, postoperative recovery, total hip arthroplasty, elderly patients

Abstract Background In the context of COVID-19, NHS Child and Adolescent Mental Health Services (CAMHS) and other children’s mental health services have faced major challenges in providing psychological treatments that (i) work when delivered remotely and (ii) can be delivered efficiently to manage increases in referrals as social distancing measures have been relaxed. Anxiety problems are a common reason for referral to CAMHS, children with pre-existing anxiety problems are particularly vulnerable in the context of COVID-19, and there were concerns about increases in childhood anxiety as schools reopened. The proposed research will evaluate the clinical and cost-effectiveness of a brief online parent-led cognitive behavioural treatment (CBT) delivered by the OSI (Online Support and Intervention for child anxiety) platform with remote support from a CAMHS therapist compared to ‘COVID-19 treatment as usual’ (C-TAU) in CAMHS and other children’s mental health services throughout the COVID-19 pandemic. Methods We will conduct a two-arm, multi-site, randomised controlled non-inferiority trial to evaluate the clinical and cost-effectiveness of OSI with therapist support compared to CAMHS and other child mental health services ‘COVID-19 treatment as usual’ (C-TAU) during the COVID-19 outbreak and to explore parent and therapists’ experiences. Discussion If non-inferiority is shown, the research will provide (1) a solution for efficient psychological treatment for child anxiety disorders while social distancing (for the COVID-19 context and future pandemics); (2) an efficient means of treatment delivery as ‘normal service’ resumes to enable CAMHS to cope with the anticipated increase in referrals; and (3) a demonstration of rapid, high-quality evaluation and application of online interventions within NHS CAMHS to drive forward much-needed further digital innovation and evaluation in CAMHS settings. The primary beneficiaries will be children with anxiety disorders and their families, NHS CAMHS teams, and commissioners who will access a potentially effective, cost-effective, and efficient treatment for child anxiety problems. Trial registration ISRCTN ISRCTN12890382 . Registered prospectively on 23 October 2020.

BackgroundLittle is known about the prognostic ability of nCD64 in critically ill patients. This study aimed to assess the prognostic values of nCD64 in adult ICU patients with sepsis.MethodsA prospective cohort study was conducted at the ICU of Cho Ray Hospital in Vietnam between January 2019 to September 2020. All newly admitted 86 septic patients diagnosed based on sepsis-3 criteria were included. An evaluation of nCD64 was performed at admission (T0) and 48 h thereafter (T48). Delta nCD64 (nCD64 T48 – nCD64 T0), %delta nCD64 [(nCD64 T48 – nCD64 T0)/nCD64 T0 x 100%], APACHE II and SOFA scores were calculated and examined. Serum procalcitonin levels and white blood cell counts were documented. Spearman’s rank correlation coefficient was used to test the correlation between nCD64 and severity scores. Receiver-operating characteristic (ROC) curve was performed to evaluate the predictive efficacy of the sepsis parameters.ResultsPatients with septic shock had significantly higher nCD64 levels than septic patients [3,568 (2,589; 5,999) vs. 1,514 (1,416;2,542) molecules/cell, p

Introduction: Patient-derived induced pluripotent stem cells (iPSCs) have been widely used as disease models to test new therapeutic strategies. Moreover, the regenerative potential of stem cells can be improved with the use of biologically active compounds. Our study was designed to explore the effect of honokiol, a small polyphenol molecule extracted from Magnolia officinalis, on the survival and culture time of iPSC-derived neurons from a sporadic Alzheimer’s disease (AD) patient. This study aimed to generate iPSCs from peripheral blood mononuclear cells (PBMCs) of an AD patient using episomal plasmids with a nucleofector system and differentiate them into neurons. These iPSC-derived neurons were used to investigate the effect of honokiol extracted from M. officinalis on their survival and long-term cultures. Methods: IPSCs were generated from PBMCs of an AD patient by introducing Oct-3/4, Sox2, Klf4, L-Myc, and Lin28 using Nucleofector™ Technology. Differentiation of neurons derived from iPSCs was carried out using inducers and recognized by biomarkers. The viability of iPSC-derived neurons with the addition of honokiol extracted from the bark of M. officinalis was determined by the MTT analytical kit. Results: IPSCs were generated by reprogramming AD patient-derived PBMCs and subsequently converted into neurons. The survival and growth of iPSC-derived neurons were significantly enhanced by adding honokiol in the experiment conditions. Conclusion: AD iPSC-derived neurons had a high viability rate when cultured in the presence of honokiol. These results have shown that AD iPSC-derived neurons can be an excellent model for screening neurotrophic agents and improving the conditions for long-term cultures of human iPSC-derived neurons. Honokiol proves to be a potential candidate for cellular therapeutics against neurodegenerative disorders.

Background and Objectives: The diagnosis and pathology of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) remain under debate. However, there is a growing body of evidence for an autoimmune component in ME/CFS caused by the Epstein-Barr virus (EBV) and other viral infections. Materials and Methods: In this work, we analyzed a large public dataset on the IgG antibodies to 3054 EBV peptides to understand whether these immune responses could help diagnose patients and trigger pathological autoimmunity; we used healthy controls (HCs) as a comparator cohort. Subsequently, we aimed at predicting the disease status of the study participants using a super learner algorithm targeting an accuracy of 85% when splitting data into train and test datasets. Results: When we compared the data of all ME/CFS patients or the data of a subgroup of those patients with non-infectious or unknown disease triggers to the data of the HC, we could not find an antibody-based classifier that would meet the desired accuracy in the test dataset. However, we could identify a 26-antibody classifier that could distinguish ME/CFS patients with an infectious disease trigger from the HCs with 100% and 90% accuracies in the train and test sets, respectively. We finally performed a bioinformatic analysis of the EBV peptides associated with these 26 antibodies. We found no correlation between the importance metric of the selected antibodies in the classifier and the maximal sequence homology between human proteins and each EBV peptide recognized by these antibodies. Conclusions: In conclusion, these 26 antibodies against EBV have an effective potential for disease diagnosis in a subset of patients. However, the peptides associated with these antibodies are less likely to induce autoimmune B-cell responses that could explain the pathogenesis of ME/CFS.

Abstract Background Acute-on-chronic liver failure (ACLF) represents a rising global healthcare burden, characterised by increasing prevalence among patients with decompensated cirrhosis who have a 28-day transplantation-free mortality of 33.9%. Due to disease complexity and a high prevalence of socio-economic disadvantage, there are deficits in quality of care and adherence to guideline-based treatment in this cohort. Compared to other chronic conditions such as heart failure, those with liver disease have reduced access to integrated ambulatory care services. The LivR Well programme is a multidisciplinary intervention aimed at improving 28-day mortality and reducing 30-day readmission through a home-based, liver optimisation programme implemented in the first 28 days after an admission with either ACLF or hepatic decompensation. Outcomes from our feasibility study suggest that the intervention is safe and acceptable to patients and carers. Methods We will recruit adult patients with chronic liver disease from the emergency departments, in-patient admissions, and an ambulatory liver clinic of a multi-site quaternary health service in Melbourne, Australia. A total of 120 patients meeting EF-Clif criteria will be recruited to the ACLF arm, and 320 patients to the hepatic decompensation arm. Participants in each cohort will be randomised to the intervention arm, a 28-day multidisciplinary programme or to standard ambulatory care in a 1:1 ratio. The intervention arm includes access to nursing, pharmacy, physiotherapy, dietetics, social work, and neuropsychiatry clinicians. For the ACLF cohort, the primary outcome is 28-day mortality. For the hepatic decompensation cohort, the primary outcome is 30-day re-admission. Secondary outcomes assess changes in liver disease severity and quality of life. An interim analysis will be performed at 50% recruitment to consider early cessation of the trial if the intervention is superior to the control, as suggested in our feasibility study. A cost-effectiveness analysis will be performed. Patients will be followed up for 12 weeks from randomisation. Three exploratory subgroup analyses will be conducted by (a) source of referral, (b) unplanned hospitalisation, and (c) concurrent COVID-19. The trial has been registered with the Australian New Zealand Clinical Trials Registry. Discussion This study implements a multidisciplinary intervention for ACLF patients with proven benefits in other chronic diseases with the addition of novel digital health tools to enable remote patient monitoring during the COVID-19 pandemic. Our feasibility study demonstrates safety and acceptability and suggests clinical improvement in a small sample size. An RCT is required to generate robust outcomes in this frail, high healthcare resource utilisation cohort with high readmission and mortality risk. Interventions such as LivR Well are urgently required but also need to be evaluated to ensure feasibility, replicability, and scalability across different healthcare systems. The implications of this trial include the generalisability of the programme for implementation across regional and urban centres. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12621001703897 . Registered on 13 December 2021. WHO Trial Registration Data Set. See Appendix 1

Noor Shuhada Salleh,1 Li Yoong Tang,1 Subhashini Jayanath,2 Khatijah Lim Abdullah3 1Department of Nursing Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 2Developmental Pediatrics Unit, Department of Pediatrics, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 3Department of Nursing, School of Medical and Life Sciences, Sunway University, Petaling Jaya, MalaysiaCorrespondence: Li Yoong Tang, Department of Nursing Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, 50603, Malaysia, Tel +6012 9762363, Email lytang@ummc.edu.myPurpose: Children diagnosed with ASD usually have impaired social functions, exhibit repetitive, stereotyped and self-stimulatory behaviors, which make them prone to be stigmatized by the public. However, stigma not only affects those with stigmatization characteristics such as children with ASD but also tends to include other people related to them including parents. This is called affiliate stigma. However, affiliate stigma is unlikely to occur if public awareness is high. Considering that awareness of ASD is still comparatively low in this region and that, as a review of the literature showed, there have been limited studies on stigma and ASD conducted in South-East Asia, particularly in Malaysia, this study is of great significance, especially in the context of the East and other developing countries. The aim of this study was to explore parents’ experiences of caring and perceptions of affiliate stigma, resilience and quality of life (QoL) when caring for a child with ASD.Methods: This paper is part of the sequential explanatory mixed-methods study in which, after a cross-sectional study of 144 parents, a qualitative approach was used to explore parents’ experiences of caring and their perceptions of affiliate stigma, resilience, and QoL. Participants were recruited when they were accompanying their children to therapy at two tertiary public hospitals in one of the north-eastern states of Malaysia. Eleven parents of children with ASD aged 2– 12 years participated. Qualitative data analysis followed Braun and Clarke’s methodology of thematic analysis.Results: Four themes were identified: the meaning of QoL, ASD and life adjustment, perceived stigma, and resilience.Conclusion: This is the first Southeast Asian study on parent-perceived affiliate stigma, resilience, and QoL in the context of ASD. These findings can inform healthcare personnel and policymakers into day-to-day parenting realities and therefore an effort to coordinate support services across all disciplines could be made to improve outcomes for both parents and children.Keywords: autistic disorder, child, parents, social stigma, quality of life

Min Xiao,1,&ast; Di Wang,2,&ast; Guo-Ling Lin,1 Xin Lin,3 Li-Yan Tao,4 Qi-Yong Li1,5 1Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, People’s Republic of China; 2Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 3Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 4Division of Hepatobiliary and Pancreatic Surgery, Department of Nursing, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou, People’s Republic of China; 5Jinan Microecological Biomedicine Shandong Laboratory, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qi-Yong Li, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, #848 Dongxin Road, Hangzhou, 310000, People’s Republic of China, Email liqiyong@zju.edu.cnPurpose: To explore the feasibility and safety of using the left lateral decubitus position (LLDP) to perform laparoscopic liver resection (LLR) for the treatment of hepatic lesions in segment VI and/or VII.Patients and Methods: Clinical data concerning 50 patients underwent LLR including 25 patients in the LLDP and the other 25 patients in the routine operative position (ROP) at Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College (Hangzhou, China) and Shulan (Quzhou) Hospital between March 2019 and May 2022 were retrospectively analyzed. All of the patients underwent LLR while in the LLDP or the ROP for the treatment of hepatic lesions located in segment VI and/or VII.Results: The preoperative clinical and laboratory parameters were comparable between the two groups (P > 0.05). All patients completed the surgery successfully. There were two patients required conversion to open resection in the ROP comparing with zero in the LLDP. The mean operative time was 256.9 ± 132.7 minutes in LLDP and 255.7 ± 92.1 minutes in ROP, while the median perioperative blood loss was 100 mL (range: 50– 300 mL) in LLDP and 200 mL (range: 50– 425 mL), respectively. The postoperative pathological examination showed that margin-negative resection was achieved all of the cases. The important postoperative parameters all returned to normal within five days after the LLR. The mean postoperative hospital stay (15.6 vs 19.3 days; p < 0.05) and the extraction of the drainage tube time (7.8 vs 10.4 days; p < 0.05) were shorter for patients in LLDP.Conclusion: The LLDP represents a safe and feasible position for performing LLR in selected patients with lesions in segment VI and/or VII. LLR in the LLDP is helpful in terms of the exposure of the surgical field and the recovery of the patient.Keywords: laparoscopic, liver resection, left lateral decubitus position

Giao Huynh,1 Hau Viet Nguyen,2 Lan Y Vo,1 Ngoc Thi Le,3 Han Thi Ngoc Nguyen4 1Faculty of Public Health, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam; 2Emergency Department, University Medical Center Ho Chi Minh City, Ho Chi Minh City, Vietnam; 3Faculty of Medicine, Nguyen Tat Thanh University, Ho Chi Minh City, Vietnam; 4Infection Control Department, University Medical Center Ho Chi Minh City, Ho Chi Minh City, VietnamCorrespondence: Hau Viet Nguyen, Emergency Department, University Medical Center Ho Chi Minh City, 215 Hong Bang Street, District 5, Ho Chi Minh City, Vietnam, Tel +84918764092, Email hau.nv@umc.edu.vn Han Thi Ngoc Nguyen, Infection Control Department, University Medical Center Ho Chi Minh City, 201 Nguyen Chi Thanh Street, District 5, Ho Chi Minh City, Vietnam, Tel +84397975519, Email han.ntn2@umc.edu.vnIntroduction: The COVID-19 pandemic has been affecting the lives of millions of people globally. Patients recovering from COVID-19 are facing, not only the symptom of long COVID, but also psychological problems, such as sleep disturbance. This study aims to assess the proportion of COVID-19 recovered adult patients that suffer from insomnia and associated factors in Vietnam.Methods: A cross-sectional study was performed between January and March 2022 among patients who have recovered from a COVID-19 infection. Data were collected based on a self-administered questionnaire that included sociodemographic and standardized questionnaires from the Hospital Anxiety and Depression Scale (HADS), the Perceived stress scale (PSS) and the dependent variable using Insomnia Severity Index (ISI). Multivariable logistic regression was conducted to explore factors associated with the patients’ insomnia disorder.Results: A total of 325 participants were included in this analysis, 34.5% of participants had insomnia. According to multivariable logistic regression, participants who were equal to and over 50 years of age, feeling alienated from others, and were not supported by families or relatives, reported significantly higher levels of insomnia disorders over those aged under 50 years, having closer ties with family and had received support from family or relatives. Besides, respondents who recorded mental health problems that included anxiety, depression and stress were more likely to get insomnia disorders than those without mental health symptoms (OR 2.7, 95% CI 1.1– 6.6) (OR 4.5, 95% CI 2.3– 8.9) (OR 2.3, 95% CI 1.1– 5.3), respectively, all p < 0.05.Conclusion: There was a remarkable rate of COVID-19 recovered patients experiencing insomnia disorders. Older age, alienated relationships and not being supported by families or relatives, as well as had mental health problems, are factors that affected the patients’ insomnia, which showed that these sleep issues need to be screened and managed among adults who have recovered from COVID-19.Keywords: COVID-19, insomnia, recovery, sleep disturbance, Vietnam

Background: Educational interventions have been shown to be effective in reducing cancer pain for patients with cancer. However, there is a lack of educational intervention programs for cancer pain management in Vietnam, and none have been studied or implemented in clinical practice. Objective: This study aimed to evaluate the cultural appropriateness and clinical applicability of a pain management educational intervention program modified from PRO-SELF©: Pain Control Program for patients with cancer. Methods: This quantitative descriptive study was conducted from January to June 2022 with 15 experts, including oncologists, nurses with palliative care and pain relief certifications, and pharmacists. Data were collected using a 23-item questionnaire rated on a 5-point scale and analyzed using descriptive statistics. Results: The program was evaluated for its appropriateness, clinical applicability, and feasibility, resulting in high ratings with an average of 4.49 ± 0.23, 4.56 ± 0.33, and 4.29 ± 0.55, respectively. The general mean score of the items was 4.46 ± 0.22. Experts also provided comments for adjustments to the program, which were incorporated into a revised draft of the intervention program. Conclusions: The pain management educational intervention program for Vietnamese patients with cancer was considered appropriate and clinically applicable by the experts. Further clinical trials can now be conducted to evaluate the program’s effectiveness.