Impacts of COVID-19 pandemic prevention measures to the palliative care in Taiwan.

Background: Prevention measures for palliative care and the provision of discharge planning services for inpatients in Taiwan before and during the COVID-19 pandemic had not been investigated. This study was aimed to investigate the factors associated with heightened palliative care needs and increased mortality rates. Methods: This research adopts a retrospective case-control study design. The investigation encompasses patients admitted before the pandemic (from January 1, 2019, to May 31, 2019) and during the COVID-19 pandemic (from January 1, 2020, to May 31, 2020). The case group consisted of 231 end-of-life inpatients during the pandemic, control group was composed of the pool of inpatients with pre-pandemic and matched with cases by sex and age in a 1:1 ratio. Results: The results showed that the prevalence of respiratory failure symptoms (p = 0.004), residing in long-term care facilities (p = 0.017), palliative care needs assessment scores (p = 0.010), as well as the provision of guidance for nasogastric tube feeding (p = 0.002), steam inhalation (p = 0.003), turning and positioning (p < 0.001), percussion (p < 0.001), passive range of motion (p < 0.001), and blood pressure measurement (p < 0.001). Furthermore, the assessment of the necessity for assistive devices, including hospital beds, also exhibited statistically significant variations (p < 0.001). Further investigation of the factors associated with high palliative care needs and the risk of mortality for both the case and control groups. Risk factors for high palliative care needs encompassed assessments of daily activities of living, the presence of pressure ulcers, and the receipt of guidance for ambulation. Risk factors for mortality encompassed age, a diagnosis of cancer, palliative care needs assessment scores, and the provision of guidance for disease awareness. Conclusion: This research highlights the heightened risk of COVID-19 infection among end-of-life inpatients during the COVID-19 pandemic. The findings of this study may advance care planning to alleviate avoidable suffering. To meet the needs of inpatients during pandemic, healthcare professionals should undergo comprehensive palliative care training and receive policy support.

Microglia through MFG-E8 signaling decrease the density of degenerating neurons and protect the brain from the development of cortical infarction after stroke.

Neuronal loss is a hallmark of stroke and other neurodegenerative diseases, and as such, neuronal loss caused by microglia has been thought to be a contributing factor to disease progression. Here, we show that microglia indeed contribute significantly to neuronal loss in a mouse model of stroke, but this microglial-dependent process of neuronal clearance specifically targets stressed and degenerating neurons in the ischemic cortical region and not healthy non-ischemic neurons. Nonspecific stimulation of microglia decreased the density of neurons in the ischemic cortical region, whereas specific inhibition of MFG-E8 signaling, which is required for microglial phagocytosis of neurons, had the opposite effect. In both scenarios, the effects were microglia specific, as the same treatments had no effect in mice whose microglia were depleted prior to stroke. Finally, even though the inhibition of MFG-E8 signaling increased neuronal density in the ischemic brain region, it substantially exacerbated the development of cortical infarction. In conclusion, microglia through MFG-E8 signaling contribute to the loss of ischemic neurons and, in doing so, minimize the development of cortical infarction after stroke.

Carnosic acid, a novel food-source AT1R antagonist and its anti-hypertension mechanism.

Hypertension is the most prevalent non-communicable disease, affecting billions of people worldwide. Discovery and development of natural antihypertensive lead compounds or drugs are important to resolve the limitations of existing antihypertensive drug safety and resistance. This investigation verified that carnosic acid (CA), an important active ingredient of rosemary, an edible spice plant, indicates a significant anti-hypertensive activity in spontaneous hypertension rats by targeting AT1R. Moreover, our research indicated that CA shared a comparable antagonistic mechanism with established synthetic angiotensin II receptor blockers (ARBs), as it occupies the binding sites of Angiotensin II (AngII) at His6 and Pro7 within the AT1R's ligand-binding pocket. Notably, CA exerted better anti-hypertensive activity since it could not break the Asn1113.35-Asn2957.46 hydrogen bond to stabilize the AT1R inactive state. As the first potent AT1R antagonist identified in a natural food source, CA is poised to become a novel anti-hypertensive lead compound, distinguished by its unique skeleton structure different from conventional ARBs. This research lays a valuable theoretical groundwork for the future exploration of CA and rosemary extract in both fundamental studies and clinical applications.

Incidence and Progression of Diabetic Retinopathy After Cataract Surgery: A Systematic Review and Meta-Analysis.

PURPOSE: The impact of cataract surgery on diabetic retinopathy (DR) in patients with diabetes mellitus (DM) remains uncertain. This study aimed to investigate the incidence and progression of DR in patients with DM who underwent cataract surgery. DESIGN: Meta-analysis. METHODS: A systematic search of PubMed, Cochrane CENTRAL, and Embase databases was conducted from inception to April 2024. Randomized controlled trials or observational cohort studies involving adult patients with DM who underwent cataract surgery were included. Studies reporting data on the incidence or progression of postoperative DR were considered. Effect sizes were determined using risk ratios (RRs) with 95% confidence intervals (CIs), and meta-analysis was performed using a random-effects model. Subgroup analysis and meta-regression were conducted on perioperative demographic factors such as types of cataract surgery, DM durations, preoperative glycated hemoglobin A1c levels, and postoperative follow-up durations. RESULTS: Data from 15 studies, involving 7,287 patients were analyzed. Postoperative DR incidence was elevated compared to the control group (RR, 1.38; 95% CI, 1.16-1.63; p < 0.001), although not significantly different in paired studies (RR, 0.85; 95% CI, 0.39-1.83; p = 0.671). DR progression was significantly higher after cataract surgery (RR, 1.46; 95% CI, 1.28-1.66; p < 0.001), irrespective of cataract surgery type and study design. Our analysis also revealed a significant increase in DR progression to sight-threatening DR, which includes clinically significant macular edema and proliferative diabetic retinopathy, following cataract surgery (RR, 1.84; 95% CI, 1.21-2.81; p = 0.005). Additionally, various risk factors such as preoperative HbA1c level, duration of postoperative follow-up, duration of diabetic diagnosis, age, and use of insulin therapy were investigated, However, none of these parameters significantly influenced the incidence or progression of postoperative DR. CONCLUSIONS: Further research is needed to fully understand the incidence of DR after cataract surgery. However, our study provides moderate evidence supporting the progression of DR following such surgical interventions. Therefore, it is imperative to closely monitor DR progression within one year following cataract surgery in patients with DM.

Validation of multispectral imaging-based tissue oxygen saturation detecting system for wound healing recognition on open wounds.

Significance: The multispectral imaging-based tissue oxygen saturation detecting (TOSD) system offers deeper penetration ( ∼ 2 to 3 mm) and comprehensive tissue oxygen saturation ( StO 2 ) assessment and recognizes the wound healing phase at a low cost and computational requirement. The potential for miniaturization and integration of TOSD into telemedicine platforms could revolutionize wound care in the challenging pandemic era. Aim: We aim to validate TOSD's application in detecting StO 2 by comparing it with wound closure rates and laser speckle contrast imaging (LSCI), demonstrating TOSD's ability to recognize the wound healing process. Approach: Utilizing a murine model, we compared TOSD with digital photography and LSCI for comprehensive wound observation in five mice with 6-mm back wounds. Sequential biochemical analysis of wound discharge was investigated for the translational relevance of TOSD. Results: TOSD demonstrated constant signals on unwounded skin with differential changes on open wounds. Compared with LSCI, TOSD provides indicative recognition of the proliferative phase during wound healing, with a higher correlation coefficient to wound closure rate (TOSD: 0.58; LSCI: 0.44). StO 2 detected by TOSD was further correlated with proliferative phase angiogenesis markers. Conclusions: Our findings suggest TOSD's enhanced utility in wound management protocols, evaluating clinical staging and therapeutic outcomes. By offering a noncontact, convenient monitoring tool, TOSD can be applied to telemedicine, aiming to advance wound care and regeneration, potentially improving patient outcomes and reducing healthcare costs associated with chronic wounds.

Limb reduction in an Esco2 cohesinopathy mouse model is mediated by p53-dependent apoptosis and vascular disruption.

Roberts syndrome (RBS) is an autosomal recessive disorder with profound growth deficiency and limb reduction caused by ESCO2 loss-of-function variants. Here, we elucidate the pathogenesis of limb reduction in an Esco2fl/fl;Prrx1-CreTg/0 mouse model using bulk- and single-cell-RNA-seq and gene co-expression network analyses during embryogenesis. Our results reveal morphological and vascular defects culminating in hemorrhage of mutant limbs at E12.5. Underlying this abnormal developmental progression is a pre-apoptotic, mesenchymal cell population specific to mutant limb buds enriched for p53-related signaling beginning at E9.5. We then characterize these p53-related processes of cell cycle arrest, DNA damage, cell death, and the inflammatory leukotriene signaling pathway in vivo. In utero treatment with pifithrin-α, a p53 inhibitor, rescued the hemorrhage in mutant limbs. Lastly, significant enrichments were identified among genes associated with RBS, thalidomide embryopathy, and other genetic limb reduction disorders, suggesting a common vascular etiology among these conditions.

Terphenyllin induces CASP3-dependent apoptosis and pyroptosis in A375 cells through upregulation of p53.

BACKGROUND: Melanoma, one of the most lethal forms of skin cancer, has the potential to develop in any area where melanocytes are present. Currently, postoperative recurrence due to the emergence of systemic drug resistance represents a significant challenge in the treatment of melanoma. In this study, terphenyllin (TER), a distinctive inhibitory impact on melanoma cells was identified from the natural p-terphenyl metabolite. This study aimed to elucidate the intrinsic mechanism of this inhibitory effect, which may facilitate the discovery of novel chemotherapeutic agents. METHODS: A transcriptome sequencing and metabolomic analysis of TER-treated A375 cells was conducted to identify potential pathways of action. The key proteins were knocked out and backfilled using CRISPR-Cas9 technology and molecular cloning. Subsequently, the results of cytosolic viability, LDH release, immunofluorescence and flow cytometry were employed to demonstrate the cell death status of the drug-treated cells. RESULTS: The p53 signalling pathway was markedly upregulated following TER treatment, leading to the activation of CASP3 via the intrinsic apoptotic pathway. The activated CASP3 initiated apoptosis, while simultaneously continuing to cleave the GSDME, thereby triggering pyroptosis. The knockout of p53, a key protein situated upstream of this pathway, resulted in a significant rescue of TER-induced cell death, as well as an alleviation of the decrease in cell viability. However, the knockout of key proteins situated downstream of the pathway (CASP3 and GSDME) did not result in a rescue of TER-induced cell death, but rather a transformation of the cells from apoptosis and pyroptosis. CONCLUSIONS: The induction of apoptosis and pyroptosis in A375 cells by TER is mediated via the p53-BAX/FAS-CASP3-GSDME signalling pathway. This lays the foundation for TER as a potential anti-melanoma drug in the future. It should be noted that CASP3 and GSDME in this pathway solely regulate the mode of cell death, rather than determine whether cell death occurs. This distinction may prove valuable in future studies of apoptosis and pyroptosis.

Unveiling the multifaceted realm of human papillomavirus: a comprehensive exploration of biology, interactions, and advances in cancer management.

Human Papillomavirus (HPV), an extensive family of DNA viruses, manifests as a persistent global health challenge. Persistent HPV infection is now firmly established as a significant aetiological factor for a spectrum of malignancies. In this review, we examine the latest insights into HPV biology and its intricate relationship with the host. We delve into the complex dynamics of co-infections involving HPV alongside other viruses, such as HIV, EBV, and HSV, as well as the burgeoning role of the microbiome in cancer development. We also explore recent advancements in understanding the specific contributions of HPV in the development of various cancers, encompassing cancers of the anogenital region, head and neck, as well as breast, lung, and prostate. Moreover, we focus on the current preventive strategies, including vaccination and screening methods, and therapeutic interventions that range from traditional approaches like surgery and chemotherapy to emerging modalities such as targeted therapies and immunotherapies. Additionally, we provide a forward-looking view on the future directions of HPV research, highlighting potential areas of exploration to further our understanding and management of HPV and its associated cancers. Collectively, this review is positioned to deepen readers' understanding of HPV biology and its complex interplay with cancer biology. It presents innovative strategies for the prevention, management, and therapeutic intervention of HPV-associated malignancies.

Fully human monoclonal antibodies against Ebola virus possess complete protection in a hamster model.

Ebola disease is a lethal viral hemorrhagic fever caused by ebolaviruses within the Filoviridae family with mortality rates of up to 90%. Monoclonal antibody (mAb) based therapies have shown great potential for the treatment of EVD. However, the potential emerging ebolavirus isolates and the negative effect of decoy protein on the therapeutic efficacy of antibodies highlight the necessity of developing novel antibodies to counter the threat of Ebola. Here, 11 fully human mAbs were isolated from transgenic mice immunized with GP protein and recombinant vesicular stomatitis virus-bearing GP (rVSV-EBOV GP). These mAbs were divided into five groups according to their germline genes and exhibited differential binding activities and neutralization capabilities. In particular, mAbs 8G6, 2A4, and 5H4 were cross-reactive and bound at least three ebolavirus glycoproteins. mAb 4C1 not only exhibited neutralizing activity but no cross-reaction with sGP. mAb 7D8 exhibited the strongest neutralizing capacity. Further analysis on the critical residues for the bindings of 4C1 and 8G6 to GPs was conducted using antibodies complementarity-determining regions (CDRs) alanine scanning. It has been shown that light chain CDR3 played a crucial role in binding and neutralization and that any mutation in CDRs could not improve the binding of 4C1 to sGP. Importantly, mAbs 7D8, 8G6, and 4C1 provided complete protections against EBOV infection in a hamster lethal challenge model when administered 12 h post-infection. These results support mAbs 7D8, 8G6, and 4C1 as potent antibody candidates for further investigations and pave the way for further developments of therapies and vaccines.

A Regenerable Bi-based Catalyst for Efficient and Stable Electrochemical CO2 Reduction to Formate at Industrial Current Densities.

Renewable electricity shows immense potential as a driving force for the carbon dioxide reduction reaction (CO2RR) in production of formate (HCOO-) at industrial current density, providing a promising path for value-added chemicals and chemical manufacturing. However, achieving high selectivity and stable production of HCOO- at industrial current density remains a challenge. Here, we present a robust Bi0.6Cu0.4 NSs catalyst capable of regenerating necessary catalytic core (Bi-O) through cyclic voltammetry (CV) treatment. Notably, at 260 mA cm-2, faradaic efficiency of HCOO- reaches an exceptional selectivity to 99.23%, maintaining above 90% even after 400h, which is longest reaction time reported at industrial current density. Furthermore, in stability test, the catalyst was constructed by CV reconstruction to achieve stable and efficient production of HCOO-. In 20h reaction test, the catalyst has a rate of HCOO- production of 13.24mmol m-2 s-1, a HCOO- concentration of 1.91mol L-1, and an energy consumption of 129.80kWh kmol-1. In-situ Raman spectroscopy reveals the formation of Bi-O structure during the gradual transformation of catalyst from Bi0.6Cu0.4 NBs to Bi0.6Cu0.4 NSs. Theoretical studies highlight the pivotal role of Bi-O structure in modifying the adsorption behavior of reaction intermediates, which further reduces energy barrier for *OCHO conversion in CO2RR.

IVF and obstetric outcomes among women of advanced maternal age (≥45 years) using donor eggs.

RESEARCH QUESTION: Does very advanced maternal age (VAMA; age ≥45 years) influence obstetric outcomes among women using donor oocytes in IVF? DESIGN: This retrospective cohort study analysed data from a nationwide IVF registry in Taiwan, focusing on IVF cycles involving women aged 45 years and older using donated oocytes between 2007 and 2016. The study assessed cumulative live birth rates (CLBR) and secondary outcomes such as clinical pregnancy, miscarriage, live birth and twin pregnancy rates, alongside perinatal outcomes such as Caesarean section rates, pre-eclampsia, gestational diabetes and birthweight. RESULTS: The study included 1226 embryo transfer cycles from 745 women, with a stable live birth rate of about 40% across the study period. The CLBR was slightly lower in women aged 50 years and older (54.2%) compared with those aged 45-46 years (58.0%), but these differences were not statistically significant (P = 0.647). Secondary outcomes and perinatal outcomes did not significantly differ across age groups. Regression analysis suggested a non-significant trend towards a decrease in live birth rate and birthweight with increasing maternal age. The study also found that single-embryo transfer (SET) minimized the risk of twin pregnancies without significantly affecting live birth rates. CONCLUSIONS: IVF with donor oocytes remains a viable option for women of VAMA, with consistent live birth rates across age groups. However, the study underscores the importance of elective SET to reduce the risk of twin pregnancies and associated adverse outcomes. Further research is needed to explore the impact of other factors such as paternal age and embryo development stage on IVF success in this population.

Machine Learning Models Reliably Predict Clinical Outcomes in Medial Patellofemoral Ligament Reconstruction.

PURPOSE: To develop the machine learning model to predict clinical outcomes following MPFLR and identify the important predictive indicators. METHODS: This study included patients who underwent MPFLR from January 2018 to December 2022. The exclusion criteria were as follows: 1) concurrent bony procedures, 2) history of other knee surgeries, and 3) follow-up period of less than 12 months. Forty-two predictive models were constructed for seven clinical outcomes (failure to achieve MCID of clinical scores, return to pre-injury sports, pivoting sports, and recurrent instability) using six machine learning algorithms (Random Forest, Logistic Regression, Support Vector Machine, Decision Tree, implemented multilayer perceptron, and K-nearest neighbor). The performance of the model was evaluated using metrics such as the area under the receiver operating characteristic curve (AUC), accuracy, specificity, and sensitivity. Additionally, Shapley Additive Explanation summary plot was employed to identify the important predictive factors of the best-performing model. RESULTS: A total of 218 patients met criteria. For the best-performing models in predicting failure to achieve the MCID for Lysholm, IKDC, Kujala, and Tegner scores, the AUCs and accuracies were 0.884 (good) and 87.3%, 0.859 (good) and 86.2%, 0.969 (excellent) and 97.0%, and 0.760 (fair) and 76.8%, respectively; 0.952 (excellent) and 95.2% for return to pre-injury sports; 0.756 (fair) and 75.4% for return to pivoting sports; and 0.943 (excellent) and 94.9% for recurrent instability. Low preoperative Tegner score, shorter time to surgery, and absence of severe trochlear dysplasia were significant predictors for return to pre-injury sports, while absence of severe trochlear dysplasia and patellar alta were significant predictors for return to pivoting sports. Older age, female sex, and low preoperative Lysholm score were highly predictive of recurrent instability. CONCLUSION: The predictive models developed using machine learning algorithms can reliably forecast the clinical outcomes of MPFLR, particularly demonstrating excellent performance in predicting recurrent instability. LEVEL OF EVIDENCE: Level III, case-control study.

Construction of an adverse outcome pathway framework for arsenic-induced lung cancer using a network-based approach.

Environmental pollutants are considered as a cause of tumorigenesis, but approaches to assess their risk of causing tumors remain insufficient. As an alternative approach, the adverse outcome pathway (AOP) framework is used to assess the risk of tumors caused by environmental pollutants. Arsenic is a pollutant associated with lung cancer, but early assessment of lung cancer risk is lacking. Therefore, we applied the AOP framework to arsenic-induced lung cancer. A systematic review revealed increased risks of lung cancer following exposure to a range of arsenic concentrations in drinking water (OR = 1.83, 95 % CI = 1.46-2.30). We obtained, from public databases, genes related to risk of arsenic-induced lung cancer. Then, Cox and LASSO regressions were used to screen target genes from the risk genes. Subsequently, target genes, phenotypes, and pathways were used to construct the computational AOP network, which was determined by Cytoscape to have 156 edges and 45 nodes. Further, target genes, phenotypes, and pathways were used as molecular initiating events and key events to construct the AOP framework depending on upstream and downstream relationships. In the AOP framework, by Weight of Evidence, arsenic exposure increased levels of EGFR, activated the PI3K/AKT pathway, regulated cell proliferation by promoting the G1/S phase transition, and caused generation of lung cancers. External validation was achieved through arsenite-induced, malignant transformed human bronchial epithelial (HBE) cells. Overall, these results, by integration into existing data to construct an AOP framework, provide insights into the assessment of lung cancer risk for arsenic exposure. Special attention needs to be focused on populations with low-dose arsenic exposure.

Mutant IDH1 inhibition induces dsDNA sensing to activate tumor immunity.

Isocitrate dehydrogenase 1 (IDH1) is the most commonly mutated metabolic gene across human cancers. Mutant IDH1 (mIDH1) generates the oncometabolite (R)-2-hydroxyglutarate, disrupting enzymes involved in epigenetics and other processes. A hallmark of IDH1-mutant solid tumors is T cell exclusion, whereas mIDH1 inhibition in preclinical models restores antitumor immunity. Here, we define a cell-autonomous mechanism of mIDH1-driven immune evasion. IDH1-mutant solid tumors show selective hypermethylation and silencing of the cytoplasmic double-stranded DNA (dsDNA) sensor CGAS, compromising innate immune signaling. mIDH1 inhibition restores DNA demethylation, derepressing CGAS and transposable element (TE) subclasses. dsDNA produced by TE-reverse transcriptase (TE-RT) activates cGAS, triggering viral mimicry and stimulating antitumor immunity. In summary, we demonstrate that mIDH1 epigenetically suppresses innate immunity and link endogenous RT activity to the mechanism of action of a US Food and Drug Administration-approved oncology drug.

Infants' cortisol reactivity and infant-mother cortisol synchrony in urban Chinese families: The role of maternal control strategy.

Maternal control strategy refers to a mother's practices used to impel, inhibit, guide, or shape their children's behaviors during mother-child interaction. The present study examined control strategies used by Chinese urban mothers and how they associated with infants' cortisol trajectory and infant-mother cortisol synchrony during a separation task. Participants were 115 infant-mother dyads. Maternal control strategy was assessed during mother-infant free-play when the infants were 6 months (T1) and 1 year (T2) old. Salivary cortisol samples were collected from both infants and mothers during a stress-inducing task at T2. The results indicated that mothers most frequently adopted the moderate power control strategy, at both T1 and T2. T1 maternal low control strategy significantly predicted infants' cortisol response curve, namely infants of mothers who predominantly adopted a low power control strategy had a more dynamic reactivity and recovery in their cortisol response to the separation task. Positive cortisol synchrony was observed between mothers and infants during the separation stress condition. In addition, T2 maternal high power control strategy accounted for inter-individual variations in infant-mother cortisol synchrony, such that mothers who predominantly adopted a high power control strategy exhibited a heightened level of cortisol synchrony with their infants. Our findings suggest that targeted training in maternal control strategies could help mothers calibrate their infants' adrenocortical regulation.

End-tidal Carbon Dioxide Trajectory-based Prognostication of Out-of-hospital Cardiac Arrest.

Background: During cardiopulmonary resuscitation (CPR), end-tidal carbon dioxide (EtCO2) is primarily determined by pulmonary blood flow, thereby reflecting the blood flow generated by CPR. We aimed to develop an EtCO2 trajectory-based prediction model for prognostication at specific time points during CPR in patients with out-of-hospital cardiac arrest (OHCA). Methods: We screened patients receiving CPR between 2015-2021 from a prospectively collected database of a tertiary-care medical center. The primary outcome was survival to hospital discharge. We used group-based trajectory modeling to identify the EtCO2 trajectories. Multivariable logistic regression analysis was used for model development and internally validated using bootstrapping. We assessed performance of the model using the area under the receiver operating characteristic curve (AUC). Results: The primary analysis included 542 patients with a median age of 68.0 years. Three distinct EtCO2 trajectories were identified in patients resuscitated for 20 minutes (min): low (average EtCO2 10.0 millimeters of mercury [mm Hg]; intermediate (average EtCO2 26.5 mm Hg); and high (average EtCO2: 51.5 mm Hg). Twenty-min EtCO2 trajectory was fitted as an ordinal variable (low, intermediate, and high) and positively associated with survival (odds ratio 2.25, 95% confidence interval [CI] 1.07-4.74). When the 20-min EtCO2 trajectory was combined with other variables, including arrest location and arrest rhythms, the AUC of the 20-min prediction model for survival was 0.89 (95% CI 0.86-0.92). All predictors in the 20-min model remained statistically significant after bootstrapping. Conclusion: Time-specific EtCO2 trajectory was a significant predictor of OHCA outcomes, which could be combined with other baseline variables for intra-arrest prognostication. For this purpose, the 20-min survival model achieved excellent discriminative performance in predicting survival to hospital discharge.

[Study on optimal harvesting period and rational medicinal parts of Zanthoxylum nitidum based on statistics of main effective components].

To determine the optimal harvesting period and rational medicinal parts of Zanthoxylum nitidum, the main effective components of cultivated Z. nitidum samples, which originate from various growth years, harvesting months, and different parts were analyzed and compared with the wild samples. HPLC was performed on a Kinetex C18 column(4. 6 mm×100 mm, 2. 6 µm) with the gradient elution of 0. 3% phosphoric acid solution-acetonitrile(80 ∶ 20) containing 0. 2% triethylamine. The flow rate was 1. 0 m L·min-1, and the detection wavelength was 273 nm. The column temperature was 30 ℃. Nitidine chloride and chelerythrine, the main effective components, were determined as the markers. The results showed there was no significant difference in the contents of the main effective components among the roots of wild and cultivated Z. nitidum, as well as the roots and roots + stems of cultivated Z. nitidum. The statistical results of HCA and PCA indicated that the roots and stems could be clearly distinguished, but no distinction could be made between wild and cultivated products, which was consistent with the results of the significance analysis. The total contents of nitidine chloride and chelerythrine in roots and stems of Z. nitidum of 1-6 years old were 0. 114%-0. 256% and 0. 030%-0. 133%, respectively. These results suggested a positive correlation between the content of the main effective components and the growth years. No significant difference was observed between the contents of samples harvested in different seasons, indicating that the harvest season had no effect on the content of the main effective components of the Z. nitidum samples. The total contents of nitidine chloride and chelerythrine of the dried Z. nitidum samples(excluding branches) from three plantation bases were 0. 308%±0. 123% in Yunfu, 0. 192%±0. 025% in Maoming, and 0. 197%±0. 052% in Nanning, respectively, and they were all not less than 0. 15%, or in other words, the roots(including fibrous roots, taproots, and underground stems) and stems(aboveground stems) of Z. nitidum transplanted for more than 2. 5 years can meet the medical requirements. This study demonstrates that the cultivated Z. nitidum could be used as a valid substitute for the wild Z. nitidum, which provides a guarantee for the sustainable development and the application of Z. nitidum resources. The stems and roots could be considered medicinal parts of Z. nitidum. It is recommended to revise the medicinal parts of Z. nitidum to dried roots and stems in the next edition of Chinese Pharmacopoeia, and the medicinal parts can be harvested all year round. In order to ensure the content of effective components and clinical effectiveness, the root and stem should be harvested for medical use after the seedlings of Z. nitidum have been transplanted for more than three years.

Association of maternal constipation and risk of atopic dermatitis in offspring.

Objectives: Atopic dermatitis (AD) is a chronic and relapsing dermatologic disease that can affect individuals of all ages, including children and adults. The prevalence of AD has increased dramatically over the past few decades. AD may affect children's daily activities, increase their parents' stress, and increase health expenditure. Constipation is a worldwide issue and may affect the gut microbiome. Some research has indicated that constipation might be associated with risk of atopic disease. The primary objective of this retrospective cohort study was to extend and to explore the link between maternal constipation and risk of atopic dermatitis in offspring. Methods: Using the Longitudinal Health Insurance Database, a subset of Taiwan's National Health Insurance Research Database, we identified 138,553 mothers with constipation and 138,553 matched controls between 2005 and 2016. Propensity score analysis was used matching birth year, child's sex, birth weight, gestational weeks, mode of delivery, maternal comorbidities, and antibiotics usage, with a ratio of 1:1. Multiple Cox regression and subgroup analyses were used to estimate the adjusted hazard ratio of child AD. Results: The incidence of childhood AD was 66.17 per 1,000 person-years in constipated mothers. By adjusting child's sex, birth weight, gestational weeks, mode of delivery, maternal comorbidities, and received antibiotics, it was found that in children whose mother had constipation, there was a 1.26-fold risk of AD compared to the children of mothers without constipation (adjusted hazard ratio [aHR]: 1.26; 95% CI, 1.25-1.28). According to subgroup analyses, children in the maternal constipation group had a higher likelihood of AD irrespective of child's sex, birth weight, gestational weeks, mode of delivery, and with or without comorbidities, as well as usage of antibiotics during pregnancy. Compared to the non-constipated mothers, the aHR for the constipated mothers with laxative prescriptions <12 and ≥12 times within one year before the index date were 1.26; 95% CI, 1.24 -1.28 and 1.40; 95% CI, 1.29-1.52, respectively. Conclusion: Maternal constipation was associated with an elevated risk of AD in offspring. Clinicians should be aware of the potential link to atopic dermatitis in the children of constipation in pregnant women and should treat gut patency issues during pregnancy. More study is needed to investigate the mechanisms of maternal constipation and atopic diseases in offspring.

Transplant of fecal microbiota from healthy young mice relieves cognitive defects in late-stage diabetic mice by reducing metabolic disorders and neuroinflammation.

Fecal microbiota transplant (FMT) is becoming as a promising area of interest for treating refractory diseases. In this study, we investigated the effects of FMT on diabetes-associated cognitive defects in mice as well as the underlying mechanisms. Fecal microbiota was prepared from 8-week-aged healthy mice. Late-stage type 1 diabetics (T1D) mice with a 30-week history of streptozotocin-induced diabetics were treated with antibiotics for 7 days, and then were transplanted with bacterial suspension (100 µL, i.g.) once a day for 14 days. We found that FMT from healthy young mice significantly alleviated cognitive defects of late-stage T1D mice assessed in Morris water maze test. We revealed that FMT significantly reduced the relative abundance of Gram-negative bacteria in the gut microbiota and enhanced intestinal barrier integrity, mitigating LPS translocation into the bloodstream and NLRP3 inflammasome activation in the hippocampus, thereby reducing T1D-induced neuronal loss and astrocytic proliferation. FMT also reshaped the metabolic phenotypes in the hippocampus of T1D mice especially for alanine, aspartate and glutamate metabolism. Moreover, we showed that application of aspartate (0.1 mM) significantly inhibited NLRP3 inflammasome activation and IL-1ß production in BV2 cells under a HG/LPS condition. We conclude that FMT can effectively relieve T1D-associated cognitive decline via reducing the gut-brain metabolic disorders and neuroinflammation, providing a potential therapeutic approach for diabetes-related brain disorders in clinic.

Clinical features of retinal detachment treated with segmental scleral buckling.

PURPOSE: Our study aims to evaluate the surgical outcomes and clinical features of retinal detachment (RD) cases treated with segmental scleral buckling (SB), elucidating the role of segmental SB as a vital option in specific situations during the current era. METHODS: We retrospectively reviewed 128 eyes with primary rhegmatogenous RD that underwent segmental scleral buckling between November 2008 and December 2020. Clinical features and success rates were recorded and analyzed. RESULTS: A total of 128 eyes were included. The patient's ages ranged from 12 to 72 years, with a median age of 45. Most of the eyes were phakic (97%). Regarding the type of break, 47% were holes, and flap tears were found in 68 cases (53%). The break locations were superior-temporal (54%), inferior-temporal (31%), superior-nasal (9.5%), and inferior-nasal (5.5%). The length of the SB applied ranged from 3.5 to 8.0 clock hours, with a median of 6.0. Primary success was achieved in 121 eyes, and recurrence occurred in 7 eyes. All recurrent RD cases reattached after undergoing secondary VT. The causes of failure included 2 break reopens, 1 missed break, and 4 eyes with proliferative vitreoretinopathy. The single-surgery anatomic success (SSAS) rate for segmental SB was 94.5%. The final success rate was 100%. CONCLUSIONS: For phakic, low complexity retinal detachment in our study, segmental scleral buckling emerges as a surgical option with a high primary success rate and a lower incidence of complications.