Trichinella spiralis -induced immunomodulation signatures on gut microbiota and metabolic pathways in mice.

The hygiene hypothesis proposes that decreased exposure to infectious agents in developed countries may contribute to the development of allergic and autoimmune diseases. Trichinella spiralis, a parasitic roundworm, causes trichinellosis, also known as trichinosis, in humans. T. spiralis had many hosts, and almost any mammal could become infected. Adult worms lived in the small intestine, while the larvae lived in muscle cells of the same mammal. T. spiralis was a significant public health threat because it could cause severe illness and even death in humans who eat undercooked or raw meat containing the parasite. The complex interactions between gastrointestinal helminths, gut microbiota, and the host immune system present a challenge for researchers. Two groups of mice were infected with T. spiralis vs uninfected control, and the experiment was conducted over 60 days. The 16S rRNA gene sequences and untargeted LC/MS-based metabolomics of fecal and serum samples, respectively, from different stages of development of the Trichinella spiralis-mouse model, were examined in this study. Gut microbiota alterations and metabolic activity accompanied by parasite-induced immunomodulation were detected. The inflammation parameters of the duodenum (villus/crypt ratio, goblet cell number and size, and histological score) were involved in active inflammation and oxidative metabolite profiles. These profiles included increased biosynthesis of phenylalanine, tyrosine, and tryptophan while decreasing cholesterol metabolism and primary and secondary bile acid biosynthesis. These disrupted metabolisms adapted to infection stress during the enteral and parenteral phases and then return to homeostasis during the encapsulated phase. There was a shift from an abundance of Bacteroides in the parenteral phase to an abundance of probiotic Lactobacillus and Treg-associated-Clostridia in the encapsulated phase. Th2 immune response (IL-4/IL-5/IL-13), lamina propria Treg, and immune hyporesponsiveness metabolic pathways (decreased tropane, piperidine and pyridine alkaloid biosynthesis and biosynthesis of alkaloids derived from ornithine, lysine, and nicotinic acid) were all altered. These findings enhanced our understanding of gut microbiota and metabolic profiles of Trichinella -infected mice, which could be a driving force in parasite-shaping immune system maintenance.

Time Division Colorful Multiplexing Based on Carbon Nanodots with Modifiable Colors and Lifetimes.

Optical multiplexing technology plays a crucial role in various fields such as data storage, anti-counterfeiting, and time-resolved biological imaging. Nevertheless, employing single-wavelength phosphorescence for multiplexing often results in spectral overlap among the emission peaks of various channels, which can precipitate crosstalk and misinterpretation in the information-decoding process, thereby compromising the integrity and precision of the encrypted data. This paper proposes a time-divided colorful multiplexing technology based on phosphorescent carbon nanodots with different colors and lifetimes. Using different luminescence colors to symbolize varying information levels helps achieve multitiered information encryption and storage. By modulation of the lifetime and the emission wavelength, intricate information can be encoded, thereby enhancing the intricacy and security of the encryption mechanism. By assigning different data bits to each color, more information can be encoded in the same physical space. This method enables higher-density information storage and fortifies encryption, ensuring the compactness and security of information.

Gene therapy corrects the neurological deficits of mice with sialidosis.

Patients with sialidosis (mucolipidosis type I) type I typically present with myoclonus, seizures, ataxia, cherry-red spots, and blindness because of mutations in the neuraminidase 1 (NEU1) gene. Currently, there is no treatment for sialidosis. In this study, we developed an adeno-associated virus (AAV)-mediated gene therapy for a Neu1 knockout (Neu1-/-) mouse model of sialidosis. The vector, AAV9-P3-NP, included the human NEU1 promoter, NEU1 cDNA, IRES, and CTSA cDNA. Untreated Neu1-/- mice showed astrogliosis and microglial LAMP1 accumulation in the nervous system, including brain, spinal cord, and dorsal root ganglion, together with impaired motor function. Coexpression of NEU1 and protective protein/cathepsin A (PPCA) in neonatal Neu1-/- mice by intracerebroventricular injection, and less effective by facial vein injection, decreased astrogliosis and LAMP1 accumulation in the nervous system and improved rotarod performance of the treated mice. Facial vein injection also improved the grip strength and survival of Neu1-/- mice. Therefore, cerebrospinal fluid delivery of AAV9-P3-NP, which corrects the neurological deficits of mice with sialidosis, could be a suitable treatment for patients with sialidosis type I. After intracerebroventricular or facial vein injection of AAV vectors, NEU1 and PPCA are expressed together. PPCA-protected NEU1 is then sent to lysosomes, where ß-Gal binds to this complex to form a multienzyme complex in order to execute its function.

Nigrostriatal tract defects in mice with aromatic l-amino acid decarboxylase deficiency.

The development of the nigrostriatal dopaminergic (DA) pathway in the brain involves many transcriptional and chemotactic molecules, and a deficiency of these molecules can cause nigrostriatal tract defects. However, the role of the end product, dopamine, in nigrostriatal pathway development has not been described. In the present study, we analyzed a mouse model of congenital dopamine and serotonin deficiency, namely, the aromatic l-amino acid decarboxylase (AADC) deficiency (DdcKI) mouse model. We found via tyrosine hydroxylase (TH) immunofluorescence staining that the number of DA fibers in the stratum of 14-day-old DdcKI mice decreased. In TH-stained cleared whole brains of DdcKI mice, the numbers of DA neurons in the substantia nigra (SN) and the number of DA nerve bundles leaving the SN were both normal. However, we found that the nigrostriatal bundles in DdcKI mice were dispersed, taking aberrant routes to the striatum and spreading over a wide area. The total volume occupied by the nigrostriatal tract was increased, and the fraction of TH staining in the tract was decreased in DdcKI mice. Single-nucleus RNA sequencing analysis for mice 0, 7, and 14 days of age, revealed delayed axonogenesis and synapse formation in the striatum of DdcKI mice. The CellChat program inferred less cell-cell communication between striatal D1/D2 neurons but increased cell-cell communication involving neural precursors in DdcKI mice. Therefore, a congenital deficiency in dopamine affects nigrostriatal axon extension and striatal innervation. These nigrostriatal tract defects may limit the treatment efficacy for patients with TH or AADC deficiency.

Thermally Enhanced Phosphorescent Carbon Nanodots for Monitoring Cold-Chain Logistics.

Room-temperature phosphorescent materials, renowned for their long luminescence lifetimes, have garnered significant attention in the field of optical materials. However, the challenges posed by thermally induced quenching have significantly hindered the advancement of luminescence efficiency and stability. In this study, thermally enhanced phosphorescent carbon nanodots (CND) are developed by incorporating them into fiber matrices. Remarkably, the phosphorescence lifetime of the thermally enhanced CND exhibits a twofold enhancement, increasing from 326 to 753 ms, while the phosphorescence intensity experienced a tenfold enhancement, increasing from 25 to 245 as the temperature increased to 373 K. Rigid fiber matrices can effectively suppress the non-radiative transition rate of triplet excitons, while high temperatures can desorb oxygen adsorbed on the surface of the CND, disrupting the interaction between the CND and oxygen. Consequently, a thermally enhanced phosphorescence is obtained. In addition, benefiting from the thermally enhanced phosphorescence property of CND, a warning indicator with an anti-counterfeiting function for monitoring cold-chain logistics is demonstrated based on CND.

Using cryoprobes of different sizes combined with cone-beam computed tomography-derived augmented fluoroscopy and endobronchial ultrasound to diagnose peripheral pulmonary lesions: a propensity-matched study.

BACKGROUND: Endobronchial ultrasound (EBUS) and cone-beam computed tomography-derived augmented fluoroscopy (CBCT-AF) are utilized for the diagnosis of peripheral pulmonary lesions (PPLs). Combining them with transbronchial cryobiopsy (TBC) can provide sufficient tissue for genetic analysis. However, cryoprobes of different sizes have varying degrees of flexibility, which can affect their ability to access the target bronchus and potentially impact the accuracy. The aim of this study was to compare the diagnostic efficacy of cryoprobes of varying sizes in CBCT-AF and EBUS for the diagnosis of PPLs. METHODS: Patients who underwent endobronchial ultrasound-guided transbronchial biopsy (EBUS-TBB) and TBC combined with CBCT-AF for PPLs diagnosis between January 2021 and May 2022 were included. Propensity score matching and competing-risks regression were utilized for data analysis. Primary outcome was the diagnostic accuracy of TBC. RESULTS: A total of 284 patients underwent TBC, with 172 using a 1.7-mm cryoprobe (1.7 group) and 112 using a 1.1-mm cryoprobe (1.1 group). Finally, we included 99 paired patients following propensity score matching. The diagnostic accuracy of TBC was higher in the 1.1 group (80.8% vs. 69.7%, P = 0.050), with a similar rate of complications. Subgroup analysis also revealed that the 1.1 group had better accuracy when PPLs were located in the upper lobe (85.2% vs. 66.1%, P = 0.020), when PPLs were smaller than 20 mm (78.8% vs. 48.8%, P = 0.008), and when intra-procedural CBCT was needed to be used (79.5% vs. 42.3%, P = 0.001). TBC obtained larger specimens than TBB in both groups. There is still a trend of larger sample size obtained in the 1.7 group, but there is no statistically different between our two study groups (40.8 mm2 vs. 22.0 mm2, P = 0.283). CONCLUSIONS: The combination of TBC with CBCT-AF and EBUS is effective in diagnosing PPLs, and a thin cryoprobe is preferred when the PPLs located in difficult areas.

Optimizing surgical strategies for retroperitoneal liposarcoma: a comprehensive evaluation of standardized aggressive surgical policies.

BACKGROUND: Retroperitoneal liposarcoma (RLPS) constitutes the majority of retroperitoneal sarcomas. While surgical resection remains the sole curative approach, determining the optimal surgical strategy for RLPS remains elusive. This study addresses the ongoing debate surrounding the optimal surgical strategy for RLPS. METHODS: We recruited 77 patients with RLPS who underwent aggressive surgical policies. Patients were categorized into three surgical subtypes: suprapancreatic RLPS, pancreatic RLPS, and subpancreatic RLPS. Our standardized surgical strategy involved resecting macroscopically uninvolved adjacent organs according to surgical subtypes. We collected clinical, pathological and prognostic data for analyses. RESULTS: The median follow-up was 45.5 months. Overall survival (OS) and recurrence-free survival (RFS) were significantly correlated with multifocal RLPS, pathological subtype, recurrent RLPS and histological grade (P for OS = 0.011, 0.004, 0.010, and < 0.001, P for RFS = 0.004, 0.001, < 0.001, and < 0.001, respectively). The 5-Year Estimate OS of well-differentiated liposarcoma (WDLPS), G1 RLPS, de novo RLPS and unifocal RLPS were 100%, 89.4%, 75.3% and 69.1%, respectively. The distant metastasis rate was 1.4%. The morbidity rates (≥ grade III) for suprapancreatic, pancreatic, and subpancreatic RLPS were 26.7%, 15.6%, and 13.3%, respectively. The perioperative mortality rate is 2.6%. CONCLUSIONS: Standardized aggressive surgical policies demonstrated prognostic benefits for RLPS, particularly for G1 RLPS, WDLPS, unifocal RLPS, and de novo RLPS. This approach effectively balanced considerations of adequate exposure, surgical safety, and thorough removal of all fat tissue. G1 RLPS, WDLPS, unifocal RLPS, and de novo RLPS could be potential indications for aggressive surgical policies.

Morphology and Alignment Transition of Hexabenzocoronene (HBC) Mesogen Films by Bar Coating: Effect of Coating Speed.

Films of the discotic liquid crystalline hexabenzocoronene (HBC) derivative, HBC-1,3,5-Ph-C12, were prepared on the quartz substrate by the bar-coating method. Depending on the coating speed, regularly spaced stripes or continuous films were observed. In the former case, columns of the HBC derivatives align more along the stripes, which are perpendicular to the coating direction, whereas in the latter case, columns of the HBC derivatives in the film align more along the coating direction. These distinctive structures are confirmed via polarized optical microscopy (POM), polarized UV-vis spectroscopy, and grazing incidence small-angle X-ray scattering measurements.

Synthesis of bioactive evodiamine and rutaecarpine analogues under ball milling conditions.

Mechanochemical reactions achieved by processes such as milling and grinding are promising alternatives to traditional solution-based chemistry. This approach not only eliminates the need for large amounts of solvents, thereby reducing waste generation, but also finds applications in chemical and materials synthesis. The focus of this study is on the synthesis of quinazolinone derivatives by ball milling, in particular evodiamine and rutaecarpine analogues. These compounds are of interest due to their diverse bioactivities, including potential anticancer properties. The study examines the reactions carried out under ball milling conditions, emphasizing their efficiency in terms of shorter reaction times and reduced environmental impact compared to conventional methods. The ball milling reaction of evodiamine and rutaecarpine analogues resulted in yields of 63-78% and 22-61%, respectively. In addition, these compounds were tested for their cytotoxic activity, and evodiamine exhibited an IC50 of 0.75 ± 0.04 µg mL-1 against the Ca9-22 cell line. At its core, this research represents a new means to synthesise these compounds, providing a more environmentally friendly and sustainable alternative to traditional approaches.

The impact of long-term care insurance on healthcare utilization and expenditures among middle-aged and older Chinese adults: a quasi-experiment study.

BACKGROUND: Long-term care insurance (LTCI) is essential to alleviate the challenges of rapid aging. Research on LTCI in developing countries is limited and conclusions remain controversial. This study aims to empirically evaluate how the LTCI pilot in selected cities influences healthcare utilization and expenditures among middle-aged and older Chinese adults. METHODS: Data was from 2013, 2015, and 2018 China Health and Retirement Longitudinal Study. 167 LTCI and 8225 non-LTCI group participants were identified. Propensity score matching difference-in-difference method was used to evaluate the net effect of LTCI. The robustness of the findings was tested using a placebo test. RESULTS: In the pilot cities, around 17.8% of the population had LTCI coverage, with approximately 59.9% participating in urban employee medical insurance and 81.4% being urban residents. LTCI significantly reduced the monthly out-of-pocket outpatient expenditure by 313.764 yuan (P < 0.05), but had no significant effects on the inpatient utilization and expenditure. Further analysis of vulnerable subgroup revealed that LTCI decreased monthly outpatient visits frequency, total outpatient expenditure, and out-of-pocket outpatient expenditure by 0.523 times, 643.500 yuan, and 302.367 yuan, respectively (P < 0.05). Robustness tests confirmed the stability of these results. CONCLUSIONS: The LTCI coverage rate has remained low. While LTCI has contributed to reducing outpatient utilization and expenditure, its impact on controlling inpatient-related outcomes is limited. It is recommended to broaden LTCI coverage beyond existing participants to encompass more vulnerable populations, and improve awareness and quality of LTCI services to achieve a significant effect on inpatient care.

Community-based participatory research (CBPR) approaches in vaccination promotion: a scoping review.

BACKGROUND: Community-based participatory research (CBPR) is a collaborative research approach that engages academic researchers and community stakeholders as equal partners in all research steps to address community concerns and achieve health equity. The CBPR approach has been widely used in vaccination promotion programmes. However, the elements and steps of CBPR-based programmes varied among studies. The purpose of this scoping review was to synthesize the elements and steps, and establish an implementation framework to guide the utilisation of CBPR approaches in vaccination promotion. METHODS: This scoping review was performed in accordance with Arksey and O'Malley's five-stage framework. A systematic search was conducted on a set of electronic databases and grey literature sources. The retrieved articles were screened according to the criteria of CBPR and vaccination promotion, and data were extracted and recorded on a calibrated and predefined form in terms of study characteristics and CBPR components. Two authors worked independently to complete literature search, study selection, and data extraction. A narrative summary was used in categorising characteristics, and the contents of the included studies were summarised through qualitative analysis. RESULTS: A total of 8557 publications were initially screened, and 23 articles were finally included. According to the CBPR conceptual model, the elements in each CBPR component specifically for vaccination promotion included (1) the establishment of community-academic partnership (CAP)s, (2) community capacity building by partner training vaccination knowledge, research literacy, and service abilities and skills, (3) development and implementation of community-based intervention and (4) Outcome evaluation. A CAP was established between academic researchers or institutes and eight types of partners, including community service organisation-related non-government organisations (NGOs), health service institution-related NGOs, religious organisations, government agencies, educational institutions, media agencies, business agencies, and community representatives. The maintenance of CAP was achieved with four key strategies, namely, strengthening communication, forming management groups, sharing resources and information, and providing incentives. Twelve studies provided comprehensive insights into the strategies employed for intervention development, utilising either quantitative surveys, qualitative methods or a combination of both approaches. The contents of interventions included health service supports, health education activities, social marketing campaigns, community mobilisation, interactive discussions, vaccination reminders and incentives. As for outcome evaluation, vaccination rate and the effectiveness of interventions were assessed. A considerable increase was observed in 95.7% of the included studies (22/23), and the highest increase (92.9%) was attained after the intervention. An implementation framework was generated to summarise the elements and steps of CBPR approaches for vaccination promotion. CONCLUSIONS: This review summarised current evidence and generated an implementation framework to elucidate the elements and steps in the development and application of CBPR approaches in vaccination promotion. CBPR approaches are recommended for future vaccination promotion programmes, involving community stakeholders and research professionals, to ensure equitable access to vaccinations across diverse populations.

The joint impact of PM2.5 constituents on the risk of cerebrovascular diseases hospitalization: A large community-based cohort study.

Air pollution poses significant health risks to urban areas, with limited focus on the chronic association of PM2.5 and its constituents on cerebrovascular diseases (CERs), especially regarding the joint associations. This study explores the individual and joint associations between PM2.5 constituents and CER hospitalization risks through a cohort analysis of 36,271 adults in the Pearl River Delta, South China, from 2015 to 2020. Cox proportional hazards regression and quantile-based g-computation models were used to quantify the individual and joint associations of annual mean concentrations of PM2.5 constituents with hospitalization for CERs. 1151 participants were hospitalized due to CERs during the five-year follow-up period. Joint associations analyses identified that one quartile increase in co-exposure may result in hazard ratios of 1.530 (1.441-1.623), 1.840 (1.710-1.980), and 1.609 (1.491-1.737) for CERs, total, and ischemic stroke hospitalization, respectively. The adverse effect was primarily driven by organic matter and chlorine. Men, those with a history of tobacco or alcohol use or with low residential greenness, were more susceptible to CERs hospitalization following PM2.5 constituents co-exposure. Upcoming strategies should focus on monitoring and regulating PM2.5 constituents, encouraging healthy lifestyles, and enhancing urban greenery.

Accessibility, Cost, and Quality of an Online Regular Follow-Up Visit Service at an Internet Hospital in China: Mixed Methods Study.

BACKGROUND: Telemedicine provides remote health care services to overcome constraints of time and space in accessing medical care. Similarly, internet hospitals in China support and provide remote health care services. Due to the COVID-19 pandemic, there has been a proliferation of internet hospitals. Many new services, including online consultations and regular online follow-up visit services, can now be accessed via internet hospitals in China. However, the accessibility, cost, and quality advantages of regular online follow-up visit services remain unclear. OBJECTIVE: This study aimed to evaluate the accessibility, costs, and quality of an online regular follow-up visit service provided by an internet hospital in China. By analyzing the accessibility, costs, and quality of this service from the supply and demand sides, we can summarize the practical and theoretical experiences. METHODS: A mixed methods study was conducted using clinical records from 18,473 patients receiving 39,239 online regular follow-up visit services at an internet hospital in 2021, as well as interviews with 7 physicians, 2 head nurses, and 3 administrative staff members. The quantitative analysis examined patient demographics, diagnoses, prescriptions, geographic distribution, physician characteristics, accessibility (travel time and costs), and service hours. The qualitative analysis elucidated physician perspectives on ensuring the quality of online health care. RESULTS: Patients were predominantly middle-aged men with chronic diseases like viral hepatitis who were located near the hospital. The vast majority were from Guangdong province where the hospital is based, especially concentrated in Guangzhou city. The online regular follow-up visit service reduced travel time by 1 hour to 9 hours and costs by ¥6 to ¥991 (US $0.86-$141.32) depending on proximity, with greater savings for patients farther from the hospital. Consultation times were roughly equivalent between online and in-person visits. Physicians provided most online services during lunch breaks (12 PM to 2 PM) or after work hours (7 PM to 11 PM), indicating increased workload. The top departments providing online regular follow-up visit services were Infectious Diseases, Rheumatology, and Dermatology. The most commonly prescribed medications aligned with the prevalent chronic diagnoses. To ensure quality, physicians conducted initial in-person consultations to fully evaluate patients before allowing online regular follow-up visits, during which they communicated with patients to assess conditions and determine if in-person care was warranted. They also periodically reminded patients to come in person for more comprehensive evaluations. However, they acknowledged online visits cannot fully replace face-to-face care. CONCLUSIONS: Telemedicine services such as online regular follow-up visit services provided by internet hospitals must strictly adhere to fundamental medical principles of diagnosis, prescription, and treatment. For patients with chronic diseases, online regular follow-up visit services improve accessibility and reduce cost but cannot fully replace in-person evaluations. Physicians leverage various strategies to ensure the quality of online care.

Risk of stroke admission after long-term exposure to PM1: Evidence from a large cohort in South China.

BACKGROUND: Limited attention has been paid to the health effects of long-term PM1 exposure on stroke admission. Current investigations exploring the long-term PM exposure effect are largely based on observational studies, and PM generally is not allocated randomly to participants. Using traditional regression models might confuse messaging and hinder policy recommendations for pollution control and disease prevention policies. METHODS: We conducted a cohort study among 36,271 adults from one of the largest cities in China in 2015 and followed up through 2020. Hazard ratios of stroke admissions following long-term PM1 exposure were estimated via a causal inference approach, marginal structural time-varying Cox proportional hazard model, accounting for multiple confounders. Additionally, several sensitivity analyses and impact modification analyses were carried out. RESULTS AND DISCUSSION: Associations with 1 µg/m3 increase in long-term PM1 were identified for total (HR, 1.079; 95 %CI, 1.012-1.151) and ischemic stroke admissions (HR, 1.092; 95 %CI, 1.018-1.171). The harmful associations varied with exposure duration, initially increasing and then decreasing. The 2-3 years cumulative exposure was associated with a 3.3-5.4 % raised risk for total stroke. For every 1 µg/m³ increase in long-term PM1 exposure, females exhibited a higher risk of both total and ischemic stroke (13 % and 16 %) than men (4 % and 5 %). Low-exposure individuals (whose annual PM1 concentrations were under the third quartile among the annual concentrations for all the participants) exhibited greater sensitivity to PM1 effects (total stroke: 1.079 vs. 1.107; ischemic stroke: 1.092 vs. 1.116). The results underline the importance of safeguarding low-exposed people in highly polluted areas and suggest that long-term PM1 exposure may increase stroke admission risk, warranting attention to vulnerable groups.

Impact of coronavirus disease 2019 (COVID-19) on antimicrobial resistance among major pathogens causing healthcare-associated infection.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has caused great impact on healthcare systems, including antibiotic usage and multi-drug resistant (MDR) bacterial infections at hospitals. We aim to investigate the trends of antimicrobial resistance among the major pathogens causing healthcare-associated infection (HAI) at intensive care units (ICU). MATERIAL AND METHODS: The demographic characteristics of hospitalization, usage of antimicrobial agents, counted by half-an-year DID (defined daily dose per 1000 patient-days), and HAI density of five major MDR bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Klebsiella pneumoniae (CRKP), and carbapenem-resistant Pseudomonas aeruginosa (CRPA), of ICU patients at a medical center in Taiwan during January 2017 to December 2021 were collected and analyzed. RESULTS: The total antibiotic usage, counted by DID, had a significant increasing trend, before COVID-19 occurrence in 2017-2019, but no further increase during the pandemic period in 2020-2021. However, comparing the two time periods, antibiotics consumption was significantly increased during pandemic period. There was no significant change of HAI density in MRSA, VRE, CRAB, CRKP, and CRPA, comparing the pandemic to the pre-pandemic period. Although, CRKP and CRPA infection rates were increasing during the pre-pandemic period, there was no further increase of CRKP and CRPA HAI rates during the pandemic period. CONCLUSION: During COVID-19 pandemic, there was no significant increase in HAI density of five major MDR bacteria at ICU in Taiwan, despite increased antibiotic usage. Strict infection prevention measures for COVID-19 precautions and sustained antimicrobial stewardship probably bring these effects.

Impact of Telemedicine on Blood Glucose Control and Ophthalmic Screenings for Patients with Diabetes in Remote Areas During the COVID-19 Pandemic: A Real-World Study in Northern Taiwan.

Introduction: The purpose of this study was to assess the impact of telemedicine on ophthalmic screening and blood glucose control for patients with diabetes in remote areas of Northern Taiwan during the coronavirus disease 2019 (COVID-19) pandemic. Methods: Telemedicine was implemented in Shiding and Wanli Districts using a 5G platform from April 2021 to December 2022. Patients with poorly controlled diabetes received real-time consultations from endocrinologists at Far Eastern Memorial Hospital, 50 km away, for medication adjustment, diet control, and lifestyle recommendations. The study also provided cloud-upload blood glucose meters for self-monitoring and regular medical advice from hospital nurses. Ophthalmic screenings included fundus imaging, external eye image, and intraocular pressure measurement, with instant communication and diagnosis by ophthalmologists through telemedicine. A satisfaction questionnaire survey was conducted. Results: The study enrolled 196 patients with diabetes. Blood glucose and glycosylated hemoglobin levels were significantly reduced after applying telemedicine (p = 0.01 and p = 0.005, respectively). Ophthalmic screenings led to hospital referrals for 16.0% with abnormal fundus images, 15.6% with severe cataract or anterior segment disorders, and 27.9% with ocular hypertension or glaucoma. Fundus screening rates remained high at 86.3% and 80.4% in 2022, mainly using telemedicine, comparable with the traditional screening rate in the past 5 years. The overall satisfaction rate was 98.5%. Conclusions: Telemedicine showed effectiveness and high satisfaction in managing diabetes and conducting ophthalmic screenings in remote areas during the COVID-19 pandemic. It facilitated early diagnosis and treatment of ocular conditions while maintaining good blood glucose control and fundus screening rates.

Identification and analysis of miRNAs differentially expressed in male and female Trichosanthes kirilowii maxim.

Trichosanthes kirilowii Maxim. (TK) is a dioecious plant in the Cucurbitaceae family of which different sexes have separate medicinal uses. We used Illumina high-throughput sequencing technology to sequence miRNAs from male and female flower buds of TK. We performed bioinformatics analysis, miRNA identification, and target gene prediction on the data obtained from sequencing, and association analysis was performed in combination with the results of a previous transcriptome sequencing study. As a result, there were 80 differentially expressed miRNAs (DESs) between the female and male plants (48 upregulated and 32 downregulated in female plants). Moreover, 27 novel miRNAs in DESs were predicted to have 282 target genes, and 51 known miRNAs were predicted to have 3418 target genes. By establishing a regulatory network between miRNAs and target genes, 12 core genes were screened, including 7 miRNAs and 5 target genes. Among them, tkmiR157a-5p, tkmiR156c, tkmiR156_2, and tkmiR156k_2 jointly target the regulation of tkSPL18 and tkSPL13B. These two target genes are specifically expressed in male and female plants, respectively, and are involved in the biosynthesis process of BR, which is closely related to the sex differentiation process of TK. The identification of these miRNAs will provide a reference for the analysis of the sex differentiation mechanism of TK.

Using the deformity index of vital structures to predict outcome of patients with large vestibular schwannomas after Gamma Knife radiosurgery.

PURPOSE: Microsurgery is the mainstay of treatment for large vestibular schwannomas (VS), but the benefits of radiosurgery remain incompletely defined. Here, we aim to use automated volumetric analysis software to quantify the degree of brain stem deformity to predict long-term outcomes of patients with large VS following GKRS. METHODS: Between 2003 and 2020, 39 patients with large VS (volume > 8 cc) undergoing GKRS with a margin dose of 10-12 Gy were analyzed. The reconstruction 3D MRI was used to evaluate the extent of deformity for predicting the long-term outcome of patients. RESULTS: Their mean tumor volume was 13.7 ± 6.3 cc, and their mean follow-up after GKRS was 86.7 ± 65.3 months. Favorable clinical outcome was observed in 26 (66.7%) patients, while 13 (33.3%) patients had treatment failure. Patients with small tumor volumes, low vital structure deformity indice [(TV/(BSV + CerV) and (TV + EV)/(BSV + CerV)], and long distance of tumor to the central line were more likely to have favorable clinical outcome after GKRS. Significant prognostic value was with tumor shrinkage ratio (< 50%) were CV, CV/TV, TV/CerV, (TV + EV)/(BSV + CerV), and the distance of tumor to the central line. In cox regression, favorable clinical outcome was correlated with the Charlson comorbidity index and cochlear dosage (both p < 0.05). In multivariant analysis, tumor regression was highly correlated with the CV/TV ratio (p < 0.001). CONCLUSIONS: The brainstem deformity ratio is likely a useful index to assess the clinical and tumor regression outcomes. Clinical outcomes are multifactorial and the tumor regression was highly correlated with the ratio of cystic components.

MOAP-1-mediated dissociation of p62/SQSTM1 bodies releases Keap1 and suppresses Nrf2 signaling.

Nrf2 signaling is vital for protecting cells against oxidative stress. However, its hyperactivation is frequently found in liver cancer through excessive build-up of p62/SQSTM1 bodies that sequester Keap1, an adaptor of the E3-ubiquitin ligase complex for Nrf2. Here, we report that the Bax-binding protein MOAP-1 regulates p62-Keap1-Nrf2 signaling through disruption of p62 bodies. Upon induction of cellular stresses that stimulate formation of p62 bodies, MOAP-1 is recruited to p62 bodies and reduces their levels independent of the autophagy pathway. MOAP-1 interacts with the PB1-ZZ domains of p62 and interferes with its self-oligomerization and liquid-liquid phase separation, thereby disassembling the p62 bodies. Loss of MOAP-1 can lead to marked upregulation of p62 bodies, enhanced sequestration of Keap1 by p62 and hyperactivation of Nrf2 antioxidant target genes. MOAP-1-deficient mice exhibit an elevated tumor burden with excessive levels of p62 bodies and Nrf2 signaling in a diethylnitrosamine (DEN)-induced hepatocarcinogenesis model. Together, our data define MOAP-1 as a negative regulator of Nrf2 signaling via dissociation of p62 bodies.

Cone-beam computed tomography image-guided percutaneous microwave ablation for lung nodules in a hybrid operating room: an initial experience.

OBJECTIVES: The experience of thermal ablation of lung lesions is limited, especially performing the procedure under localisation by cone-beam CT in the hybrid operation room (HOR). Here, we present the experience of microwave ablation (MWA) of lung nodules in the HOR. METHODS: We reviewed patients who underwent image-guide percutaneous MWA for lung nodules in the HOR under general anaesthesia between July 2020 and July 2022. The workflow in the HOR including the pre-procedure preparation, anaesthesia consideration, operation methods, and postoperative care was clearly described. RESULTS: Forty lesions in 33 patients who underwent MWA under general anaesthesia (GA) in the HOR were analysed. Twenty-seven patients had a single pulmonary nodule, and the remaining six patients had multiple nodules. The median procedure time was 41.0 min, and the median ablation time per lesion was 6.75 min. The median global operation room time was 115.0 min. The median total dose area product was 14881 µGym2. The median ablation volume was 111.6 cm3. All patients were discharged from the hospital with a median postoperative stay of 1 day. Four patients had pneumothorax, two patients had pleural effusion during the first month of outpatient follow-up, and one patient reported intercostal neuralgia during the 3-month follow-up. CONCLUSIONS: Thermal ablation of pulmonary nodules under GA in the HOR can be performed safely and efficiently if we follow the workflow provided. The procedure provides an alternative to managing pulmonary nodules in patients. CLINICAL RELEVANCE STATEMENT: Thermal ablation of pulmonary nodules under GA in the HOR can be performed safely and efficiently if the provided workflow is followed. KEY POINTS: • We tested the feasibility of microwave ablation of lung lesions performed in a hybrid operating room. • To this end, we provide a description of microwave ablation of the lung under cone-beam CT localisation. • We describe a workflow by which ablation of the pulmonary nodule can be performed safely under general anaesthesia.