Direct Synthesis of Tertiary Phosphines via Alkoxide-Mediated Deborylative Phosphination of Organoboronates.

The direct transformation of alkylboron has emerged as a versatile and powerful methodology for creating carbon-carbon and carbon-heteroatom bonds. However, its potential application in the formation of carbon and phosphorus remains unexplored. In this study, we present an alkoxide base-promoted reaction system that enables deborylative phosphination of benzylic organoboronates and geminal bis(boronates) via selective C-B bond cleavage. This approach allows for the synthesis of valuable tertiary phosphines in good yields under mild conditions. The practicality and industrial potential of this approach are underscored by the operational simplicity, broad substrate scope, and easy scalability.

Effects of virtual reality-based cognitive interventions on cognitive function and activity of daily living among stroke patients: Systematic review and meta-analysis.

AIMS: To examine the effects of virtual reality-based cognitive interventions on cognitive function and activities of daily living among stroke patients, and to identify the optimal design for such intervention. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, EMBASE, Cochrane, CINANL, JBI-EBP and Web of Science from inception to October 2023. METHODS: Methodological quality was assessed by Risk of Bias Tool. Meta-analyses were assessed by Review Manager 5.4. Subgroup analyses were conducted to explore the influence of study design. Grading of Recommendations Assessment, Development and Evaluation approach was adopted to assess the certainty of evidence. RESULTS: Twenty-five randomized controlled trials (1178 participants) were included. Virtual reality-based cognitive interventions demonstrated moderate-to-large effects in improving global cognitive function (SMD = 0.43; 95% CI [0.01, 0.85]), executive function (SMD = 0.84; 95% CI [0.25, 1.43]) and memory (SMD = 0.65; 95% CI [0.15, 1.16]) compared to control treatments. No significant effects were found on language, visuospatial ability and activities of daily living. Subgroup analyses indicated one-on-one coaching, individualized design and dynamic difficulty adjustment, and interventions lasting ≥ 6 weeks had particularly enhanced effects, especially for executive function. CONCLUSIONS: Virtual reality-based cognitive interventions improve global cognitive function, executive function and memory among stroke patients. IMPLICATIONS FOR THE PATIENT CARE: This review underscores the broad cognitive advantages offered by virtual technology, suggesting its potential integration into standard stroke rehabilitation protocols for enhanced cognitive recovery. IMPACT: The study identifies key factors in virtual technology interventions that effectively improve cognitive function among stroke patients, offering healthcare providers a framework for leveraging such technology to optimize cognitive outcomes in stroke rehabilitation. REPORTING METHOD: PRISMA 2020 statement. PROSPERO REGISTRATION NUMBER: CRD42022342668.

Ferrocenylselenoether and its cuprous cluster modified TiO2 as visible-light photocatalyst for the synergistic transformation of N-cyclic organics and Cr(vi).

In this study, fcSe@TiO2 and [Cu2I2(fcSe)2]n@TiO2 nanosystems based on ferrocenylselenoether and its cuprous cluster were developed and characterized by X-ray photoelectron spectroscopy (XPS), high-resolution transmission electron microscopy (HR-TEM), energy dispersive X-ray spectroscopy (EDX), and electron paramagnetic resonance (EPR). Under optimized conditions, 0.2 g L-1 catalyst, 20 mM H2O2, and initial pH 7, good synergistic visible light photocatalytic tetracycline degradation and Cr(vi) reduction were achieved, with 92.1% of tetracycline and 64.5% of Cr(vi) removal efficiency within 30 minutes. Mechanistic studies revealed that the reactive species ˙OH, ˙O2-, and h+ were produced in both systems through the mutual promotion of Fenton reactions and photogenerated charge separation. The [Cu2I2(fcSe)2]n@TiO2 system additionally produced 1O2 from Cu+ and ˙O2-. The advantages of the developed nanosystems include an acidic surface microenvironment provided by Se⋯H+, resourceful product formation, tolerance of complex environments, and excellent adaptability in refractory N-cyclic organics.

Product-State Distributions of Three-Body Recombination in Zero-Collision-Energy 4He2-Alkaline-Earth-Metal Systems.

The distributions of product states after three-body recombination (TBR) of zero-collision-energy 4He2X systems, with X being 9Be, 24Mg, 40Ca, 88Sr, or 138Ba, are investigated in the hyperspherical representation by quantum mechanically solving the Schrödinger equation. It is found that the weakly bound (dimer) product states are preferentially populated for all of these cases, which could be understood from the joint effects of the lowest incident channel and the relatively long-range behavior of the corresponding nonadiabatic couplings among these lowest incident and shallow recombination channels. For the strongly bound products, since the flow is accessible in the small hyperradial region, their distributions are closely related to the behavior of the nonadiabatic couplings among the corresponding deep recombination channels. Particularly, our results indicate that the products are not always formed exclusively in the most weakly bound state when the scattering lengths among the reactants are relatively large and that there may exist a large fluctuation of the strongly bound products versus their binding energies in the universal region. In addition, the total TBR rates of these nonuniversal systems are also accounted for by the joint effects of the main adiabatic potentials and nonadiabatic couplings.

Effects of mindfulness-based interventions on neuropsychiatric symptoms and psychological well-being on people with subjective cognitive decline and mild cognitive impairment: A meta-analysis.

OBJECTIVES: Neuropsychiatric symptoms (NPS) are highly prevalent in individuals with subjective cognitive decline (SCD) and mild cognitive impairment (MCI), and are strongly linked to accelerated cognitive decline and dementia onset. While mindfulness-based interventions have shown promise in improving psychological well-being in clinical and community settings, their efficacy for individuals in these pre-dementia stages remains unclear. This meta-analysis examined the effects of mindfulness-based interventions on NPS and psychological outcomes in these preclinical cohorts. METHODS: Eligible studies were retrieved from PubMed, EMBASE, JBI EPB, Web of Science, and Cochrane library. Two independent researchers conducted the literature search and data extraction. Cochrane Risk-of-Bias Assessment Tool was used to assess the methodological quality of included studies. Quality of evidence was evaluated using the GRADE approach. Intervention effects were estimated by Hedge's g and 95% confidence interval (CI). RESULTS: A total of 18 randomized controlled trials (including 974 participants from 21 studies) were included in the meta-analysis. The results demonstrated statistically significant immediate post-intervention effects of mindfulness-based interventions on anxiety (g = -0.30, 95% CI -0.49 to -0.11), stress (g = -0.58, 95% CI -0.91 to -0.24), and quality of life (g = 0.50, 95% CI 0.12-0.87). However, no significant effects were found for depression, apathy, mindfulness, and stress-related biomarkers. Follow-up data analysis also did not reveal significant effects for depression and anxiety. CONCLUSIONS: The findings of this meta-analysis suggest that mindfulness-based interventions may improve anxiety, stress, and quality of life in individuals with SCD and MCI. However, more rigorous randomized controlled trials with larger sample sizes and evaluation using physiological parameters are needed to establish more definitive conclusions. Future interventions could consider incorporating cognitive training and health education to address the specific needs of the pre-dementia population. REGISTRATION NUMBER: PROSPERO: CRD42022359906.

Dauricine alleviates cognitive impairment in Alzheimer's disease mice induced by D-galactose and AlCl3 via the Ca2+/CaM pathway.

Alzheimer's disease (AD) is a common neurodegenerative disease in the elderly. Dysregulation of intracellular Ca2+ homeostasis plays a critical role in the pathological development of AD. Dauricine (DAU) is a bisbenzylisoquinoline alkaloid isolated from Menispermum dauricum DC., which can prevent the influx of extracellular Ca2+ and inhibit the release of Ca2+ from the endoplasmic reticulum. DAU has a potential for anti-AD. However, it is unclear whether DAU can exert its anti-AD effect in vivo by regulating the Ca2+ related signaling pathways. Here, we investigated the effect and mechanism of DAU on D-galactose and AlCl3 combined-induced AD mice based on the Ca2+/CaM pathway. The results showed that DAU (1 mg/kg and 10 mg/kg for 30 days) treatment attenuated learning and memory deficits and improved the nesting ability of AD mice. The HE staining assay showed that DAU could inhibit the histopathological alterations and attenuate neuronal damage in the hippocampus and cortex of AD mice. Studies on the mechanism indicated that DAU decreased the phosphorylation of CaMKII and Tau and reduced the formation of NFTs in the hippocampus and cortex. DAU treatment also reduced the abnormally high expression of APP, BACE1, and Aß1-42, which inhibited the deposition of Aß plaques. Moreover, DAU could decrease Ca2+ levels and inhibit elevated CaM protein expression in the hippocampus and cortex of AD mice. The molecular docking results showed that DAU may have a high affinity with CaM or BACE1. DAU has a beneficial impact on pathological changes in AD mice induced by D-galactose and AlCl3 and may act by negative regulation of the Ca2+/CaM pathway and its downstream molecules such as CaMKII and BACE1.

Facile preparation of organosilanes from benzylboronates and gem-diborylalkanes mediated by KOtBu.

Methods to efficiently synthesize organosilanes are valuable in the fields of synthetic chemistry and materials science. During the past decades, boron conversion has become a generic and powerful approach for constructing carbon-carbon and other carbon-heteroatom bonds, but its potential application in forming carbon-silicon remains unexplored. Herein, we describe an alkoxide base-promoted deborylative silylation of benzylic organoboronates, geminal bis(boronates) or alkyltriboronates, allowing for straightforward access to synthetically valuable organosilanes. This selective deborylative methodology exhibits operational simplicity, broad substrate scope, excellent functional group compatibility and convenient scalability, providing an effective and complementary platform for the generation of diversified benzyl silanes and silylboronates. Detailed experimental results and calculated studies revealed an unusual mechanistic feature of this C-Si bond formation.

Redox ferrocenylseleno compounds modulate longitudinal and transverse relaxation times of FNPs-Gd MRI contrast agents for multimodal imaging and photo-Fenton therapy.

Developing a feasible way to feature longitudinal (T1) and transverse (T2) relaxation performance of contrast agents for magnetic resonance imaging (MRI) is important in cancer diagnosis and therapy. Improved accessibility to water molecule is essential for accelerating the relaxation rate of water protons around the contrast agents. Ferrocenyl compounds have reversible redox property for modulating the hydrophobicity/hydrophilicity of assemblies. Thus, they could be the candidates that can change water accessibility to the contrast agent surface. Herein, we incorporated ferrocenylseleno compound (FcSe) with Gd3+-based paramagnetic UCNPs, to obtain FNPs-Gd nanocomposites using T1-T2 MR/UCL trimodal imaging and simultaneous photo-Fenton therapy. When the surface of NaGdF4:Yb,Tm UNCPs was ligated by FcSe, the hydrogen bonding between hydrophilic selenium and surrounding water molecules accelerated their proton exchange to initially endow FNPs-Gd with high r1 relaxivity. Then, hydrogen nuclei from FcSe disrupted the homogeneity of the magnetic field around the water molecules. This facilitated T2 relaxation and resulted in enhanced r2 relaxivity. Notably, upon the near-infrared light-promoted Fenton-like reaction in the tumor microenvironment, hydrophobic ferrocene(II) of FcSe was oxidized into hydrophilic ferrocenium(III), which further increased the relaxation rate of water protons to obtain r1 = 1.90±0.12 mM-1 s-1 and r2 = 12.80±0.60 mM-1 s-1. With an ideal relaxivity ratio (r2/r1) of 6.74, FNPs-Gd exhibited high contrast potential of T1-T2 dual-mode MRI in vitro and in vivo. This work confirms that ferrocene and selenium are effective boosters that enhance the T1-T2 relaxivities of MRI contrast agents, which could provide a new strategy for multimodal imaging-guided photo-Fenton therapy of tumors. STATEMENT OF SIGNIFICANCE: T1-T2 dual-mode MRI nanoplatform with tumor-microenvironment-responsive features has been an attractive prospect. Herein, we designed redox ferrocenylseleno compound (FcSe) modified paramagnetic Gd3+-based UCNPs, to modulate T1-T2 relaxation time for multimodal imaging and H2O2-responsive photo-Fenton therapy. Selenium-hydrogen bond of FcSe with surrounding water molecules facilitated water accessibility for fast T1 relaxation. Hydrogen nucleus in FcSe perturbed the phase coherence of water molecules in an inhomogeneous magnetic field and thus accelerated T2 relaxation. In tumor microenvironment, FcSe was oxidized into hydrophilic ferrocenium via NIR light-promoted Fenton-like reaction which further increased both T1 and T2 relaxation rates; Meanwhile, the released toxic •OH performed on-demand cancer therapy. This work confirms that FcSe is an effective redox mediate for multimodal imaging-guided cancer therapy.

Total alkaloids from the seed embryo of Nelumbo nucifera Gaertn. improve cognitive impairment in APP/PS1 mice and protect Aß-damaged PC12 cells.

The seed embryo of Nelumbo nucifera Gaertn. is a famous traditional Chinese medicine and food which is considered conducive to the prevention of Alzheimer's disease (AD). In this study, the effect and mechanism of TASENN (total alkaloids from the seed embryo of Nelumbo nucifera Gaertn.) on AD mice and amyloid-ß (Aß) injured PC12 cells were evaluated. HPLC-UV analysis showed that the extracted TASENN (purity = 95.6%) mainly contains Liensinine, Isoliensinine, and Neferine (purity was 23.01, 28.02, and 44.57%, respectively). In vivo, oral treatment with TASENN (50 mg/kg/day for 28 days) improved the learning and memory functions of APP/PS1 transgenic mice, ameliorated the histopathological changes of cortical and hippocampal neurons, and inhibited neuronal apoptosis. We found that TASENN reduced the phosphorylation of Tau and the formation of neurofibrillary tangles (NFTs) in APP/PS1 mouse brain. Moreover, TASENN down-regulated the expression of APP and BACE1, ameliorated Aß deposition, and inhibited microglial proliferation and aggregation. The elevated protein expression of CaM and p-CaMKII in APP/PS1 mouse brain was also reduced by TASENN. In vitro, TASENN inhibited the apoptosis of PC12 cells injured by Aß25-35 and increased the cell viability. Aß25-35-induced increase of cytosolic free Ca2+ level and high expression of CaM, p-CaMKII, and p-Tau were decreased by TASENN. Our findings indicate that TASENN has a potential therapeutic effect on AD mice and a protective effect on PC12 cells. The anti-AD activity of TASENN may be closely related to its negative regulation of the CaM pathway.

The Expectations and Acceptability of a Smart Nursing Home Model Among Chinese Older Adults and Family Members: A Qualitative Study

Purpose@#This study aims to explore the expectations and acceptability of a smart nursing home model among Chinese older adults and their family members based on a scoping review that defines the concept of smart nursing homes. @*Methods@#A qualitative case study was employed for this research. Semi-structured, in-depth interviews and focus group discussions were conducted on WeChat. Participants were purposively sampled through snowball sampling in Hainan and Dalian, China. A total of 28 older adults aged 60–75 and six adult children were interviewed until data saturation was achieved, followed by a thematic analysis. @*Results@#The expectations of smart nursing homes include: 1) quality of care supported by governments and societies; 2) smart technology applications; 3) the presence of a skilled healthcare professional team; 4) access to and scope of basic medical services; and 5) integration of medical services. The acceptability of smart nursing homes included factors such as stakeholders’ perceived efficaciousness, usability, and collateral damages of using smart technologies, and the coping process of adoption was influenced by factors such as age, economic status, health status, education, and openness to smart technologies among older adults. @*Conclusions@#Chinese older adults and their family members have a positive perception of the smart nursing home model. The qualitative evidence regarding their expectations and acceptability of smart nursing homes contributes valuable insights for a wide range of stakeholders involved in the planning and implementation of smart nursing homes.

Expression of interleukin-31 in hypertrophic scar from postoperative incision tissue / 中华医学美学美容杂志

Objective:To explore the interleukin-31 protein expression in the hypertrophic scar of incision tissue after surgery and its underlying pathological impact.Methods:From February 2022 to February 2023, three HS patients scar tissue (HS) and their normal skin tissue (Control, NS) were obtained. Two patients were female and one patient was male. The tissues were fixed in 4% formalin and embedded in paraffin. Haematoxylin-eosin (HE) stain and immunohistochemical stain were used to evaluate the epidermal thickness, myofibroblasts of dermis and the expression level of IL-31 between HS and NS.Results:The epidermis thickness was (303.88±46.03) μm in HS group, while (133.02±17.40) μm in NS group ( t=12.60, P<0.001). The expression level of IL-31 protein was measured by IRS score and positive cell density. The IRS score was 9.89±2.03 of the basal layer in HS group and was 4.33±1.66 of the basal layer in NS group. The positive cell density was 786 343.83±159 627.97 of the basal layer in HS group ( P<0.001) and was 555 457.61±128 097.21 of the basal layer in NS group ( P=0.014). In the dermis layer, the IRS score was 7.11±1.05 in HS group and was 4.33±0.71 in NS group, the positive cell density was 156 760.97±26 046.10 in HS group ( P<0.001) and was 49 576.01±52 369.33 in NS group ( P<0.001). In the dermis layer, the count of myofibroblasts was 120.44±15.75 in HS group while was 27.39±14.89 in NS group ( t=23.79, P<0.001). Conclusions:Our study demonstrates that both myofibroblast count and IL-31 protein expression level are notably increased in HS patients. The expression of IL-31 protein is prominent in the cytoplasm of myofibroblasts, basal cells, macrophages and mast cells which could implicate that IL-31 may be a potential therapeutic target to enhance the resolution of HS.

Clinical characteristics among 67 cases of botulism in Xinjiang Uygur Autonomous Region, China / 中华神经科杂志

Objective:To investigate epidemiological and clinical characteristics of botulism, and the adverse events among those received botulinum antitoxin treatment.Methods:Patients with discharge diagnosis as botulism in the Second Affiliated Hospital of Xinjiang Medical University were enrolled between 2017 and 2021. The epidemiological and clinical characteristics were evaluated. Infection and mechanical ventilation as in-hospital outcomes according to baseline characteristics were analyzed. Patients with and without the interested outcomes were compared. The adverse outcomes among those received botulinum antitoxin treatment were investigated. Those with and without the adverse outcomes were also compared.Results:Sixty-seven cases of botulism were enrolled, and most cases got sick between January and March (32/67, 47.8%); among them 62 cases were Han ethnicity (92.5%); prevalence was highest in Aksu region (15/67, 22.4%); commonly seen symptoms and signs included fatigue (58/67, 86.6%), dysphagia (48/67, 71.6%), dizziness (42/67, 62.7%), ptosis (42/67, 62.7%), blurred vision (41/67, 61.2%), and limb weakness (35/67, 52.2%). Compared with patients without in-hospital infection ( n=52), patients with in-hospital infection ( n=15) were more likely to have severe botulism (0/52 vs 5/15, χ 2=19.79, P<0.001), diplopia (16/52, 30.8% vs 11/15, χ 2=8.77, P=0.003), dysarthria (17/52, 32.7% vs 11/15, χ 2=7.91, P=0.005), consciousness disorder (1/52, 1.9% vs 4/15, χ 2=10.32, P=0.008). Compared with patients without mechanical ventilation (62/67, 92.5%), patients with mechanical ventilation (5/67, 7.5%) were more likely to have severe botulism (5/5 vs 0/62, χ 2=41.17, P<0.001), and consciousness disorder (4/5 vs 1/62, 1.6%, χ 2=29.58, P<0.001). Among 67 cases of botulism, 19 cases (28.4%) had adverse events after receiving antitoxin treatment, with an average of 6.5 days from the antitoxin treatment beginning to the adverse event onset; among the 19 cases, 18 cases (94.7%) had rash. Age, sex, and severity did not differ between the groups with ( n=19) and without adverse events ( n=48) after receiving antitoxin treatment. Conclusions:Fatigue, dysphagia, dizziness, ptosis were the most frequent symptoms and signs in the botulism in Xinjiang Uygur Autonomous Region, China. Infection was a commonly seen complication of botulism, and proactive prevention and close monitoring were needed. Adverse events after receiving antitoxin were prevalent, and might not be associated with age, sex, and severity of botulism.

Iodine check results in edible salt in Suzhou in 2017-2021 / 公共卫生与预防医学

Objective To understand the quality status of salt iodine monitoring results at the county level and checking results at the city level from 2017 to 2021 in Suzhou，and to provide a scientific basis for the development of iodine deficiency disease（IDD）prevention and control strategies and measures.  Methods During the past five years, Suzhou CDC randomly selected 15 samples of 300 monitored salt samples from each county/district CDC each year for spot checks. The data were processed by comparative analysis of relative error and grouped data t test.  Results In the conformity of iodized salt and non-iodized salt, the sample monitoring results of some counties/districts were non-iodized salt, while the city-level test results were iodized salt. In the conformity of iodized salt and seaweed iodized salt (or enhanced salt), the sample monitoring results of county/district level were iodized salt, while the test results at the city level were seaweed iodized salt (or enhanced salt). The non-conformity was relatively concentrated in some county/district laboratories, and the total amount of non-conformity tended to increase year by year. The total number of samples with relative error of >20% between the county/district and city-level results was the least in 2021, with 6, and the most in 2018, with 25. The number of samples with relative error of >30% between the county/district and city-level results was the least in 2017 being 0, while there were 12 samples in 2018, fluctuating within a small range in the past three years. The t-test results of grouped data showed that the average value of the checking results at the city level was generally higher than the monitoring results at the county level. There were 21 pairs of data with no statistical significance (P>0.05) and 29 pairs of data with statistical significance (P<0.05) between the results at the county/district level and at the city level. Among them, there were 7 counties/districts whose sample monitoring results were not significantly different from the city-level test results in 2020, while there were 9 counties/districts whose monitoring results were statistically different from the city-level test results in 2021.  Conclusion  The data analysis results show that the monitoring data of iodized salt in Suzhou is basically reliable and accurate, but there still exist some problems. Therefore, in the future work it is necessary to strengthen the monitoring system of IDD, increase training efforts, continuously monitor and check the quality of iodized salt to provide a scientific basis for effective prevention and control of IDD.

Prevalence and influencing factors of thyroid nodules in children aged 8-10 years old in Suzhou / 公共卫生与预防医学

Objective To investigate the prevalence and influencing factors of thyroid nodules in children aged 8-10 years in Suzhou , and to provide a scientific basis for the rational prevention and treatment of iodine deficiency disorders (IDD). Methods PPS sampling method was used in this study. Questionnaire survey, physical examination and thyroid B-ultrasound examination were conducted on students aged 8-10 years. Salt samples and urine samples were collected for laboratory detection of the salt iodine and urinary iodine. Univariate and multivariate logistic regression models were used to analyze the risk factors related to thyroid nodules. Results A total of 2 048 children aged 8-10 years were included in the present survey, and the prevalence of thyroid nodules was 23.34% (478/2 048). The prevalence of nodules in boys was 20.98% (218/1 039), and the prevalence of nodules in girls was 25.77% (260/1 009). Multivariate analysis showed that gender (OR=1.338, P=0.006), height (OR=1.993, P=0.001), frequency of iodine-rich food intake (OR=0.862, P=0.048) and nutritional supplements (OR=1.469, P=0.008) were correlated with the prevalence of thyroid nodules. Conclusion The prevalence rate of thyroid nodules in children aged 8-10 years old in Suzhou is 23.34%. Female gender, higher height, regular intake of iodine-rich foods and dietary supplements are statistically associated with the prevalence of thyroid nodules, which may be risk factors for the prevalence of thyroid nodules , but further research is needed to confirm.

Progress in risk factors for gallstone formation and prevention strategies for stony stage / 国际外科学杂志

Gallstone is a common and frequent disease and frequent incidence, secondary infection and cancer seriously affect the health of patients. Academic organizations in different regions have issued multiple guidelines and consensus to promote the normative diagnosis and treatment of gallstones. However, in clinical practice, most symptomatic gallstones are treated, while the formation and prevention process of gallstones are ignored, making the concept of treating without a disease has not been strengthened.This article reviews the risk factors and mechanisms of gallstone formation, and points out the importance of effective prevention during stone formation. In the stage of gallstone formation, the high risk factors of stone formation can be analyzed through two aspects of injury factors and protective factors, and the high risk groups of stone formation can be screened out. According to the pathophysiological progression of gallstones, personalized prevention and follow-up strategies can be developed for the stone formation stage of gallstones.

Methodology and application of process analytical technology (PAT) for traditional Chinese medicine manufacturing:a review / 中国中药杂志

Owing to the advancement in pharmaceutical technology, traditional Chinese medicine industry has seen rapid development. Preferring conventional manufacturing mode, pharmaceutical enterprises of traditional Chinese medicine have no effective process detection tools and process control methods. As a result, the quality of the final products mainly depends on testing and the quality is inconsistent in the same batch. Process analytical technology(PAT) for traditional Chinese medicine manufacturing, as one of the key advanced manufacturing techniques, can break through the bottleneck in quality control of medicine manufacturing, thus improving the production efficiency and product quality and reducing the material and energy consumption. It is applicable to the process control and real-time release of advanced manufacturing modes such as intelligent manufacturing and continuous manufacturing. This paper summarized the general idea of PAT for traditional Chinese medicine manufacturing. Through the analysis of the characteristics and status quo of the technology, we summed up the methodology for the continuous application and improvement of PAT during the whole life-cycle of traditional Chinese medicine. The five key procedures(process understanding, process detection, process modeling, process control, and continuous improvement) were summarized, and the application was reviewed. Finally, we proposed suggestions for the technical and regulatory challenges in implementing PAT in traditional Chinese medicine industry. This paper aims to provide a reference for development and application of PAT in advanced manufacturing, intelligent manufacturing, and continuous manufacturing of traditional Chinese medicine industry.

Analysis of the pathogenesis and risk factors of gallstone / 中华外科杂志

Objective: To explore the pathogenesis and risk factors of gallstone formation. Methods: The findings of hepatobiliary ultrasound and related data were collected from healthy subjects who underwent a physical examination at Xuanwu Hospital of Capital Medical University from January 2012 to December 2021. A total of 98 344 healthy subjects were included in the study,including 48 241 males and 50 103 females,with a ratio of 1∶1.03,aged (42.0±15.6)years(range:14 to 97 years). The gender,age,body mass index,waist circumference,systolic pressure,diastolic pressure,ALT,AST,total bilirubin,fasting blood glucose,triglyceride,total cholesterol,low-density lipoprotein,high-density lipoprotein were collected.Healthy subjects were required to sit for at least 10 minutes before blood pressure was measured.Rresults of fasting venous blood were collected after 8 to 12 hours on an empty stomach.According to the presence of gallstones by ultrasound results, healthy subjects were divided into study group and control group. Data were analyzed by rank-sum tests and χ2 test, and risk factors for gallstone formation were explored by Logistic regression analysis. Results: The incidence of gallstones in this group was 5.42%(5 333/98 344). Among them,the incidence of gallstones in people aged 60 years and above was significantly higher than that in people under 60 years old(15.31%(2 348/15 334) vs. 3.60%(2 985/83 010), χ2=3 473.46,P<0.05).The healthy subjects were divided by age for every 10 years,and the results showed that the incidence of gallstones increased with age. The incidence of gallstones in females was 5.68%(2 844/50 103),greater than 5.16%(2 489/48 241) in males(χ2=11.81,P<0.05). Among them,1 478 cases underwent gallbladder surgical resection due to gallstones,and the operation rate was 27.71%. The operation rate reached the peak between 60 and <70 years old,and decreased after 70 years old. The results of the multivariate analysis showed that,female(OR=1.38, P<0.01),age(OR=1.58, P<0.01),body mass index≥24 kg/m2(OR=1.31, P<0.01),waist circumference≥85 cm(OR=1.24, P<0.01),fasting blood glucose>6.1 mmol/L(OR=1.18,P<0.01),total cholesterol≥5.18 mmol/L(OR=0.87, P=0.019),low-density lipoprotein≥3.37 mmol/L(OR=1.15,P=0.001) were the risk factors for gallstone formation;high-density lipoprotein≥1.55 mmol/L(OR=0.87, P<0.01) was a protective factor for gallstone formation. Conclusions: The incidence of gallstones increases with age in male and female. Gender,age,body mass index,waist circumferenc,fasting blood glucose,total cholesterol,LDL,and HDL are related factors with gallstone formation.

Sample average treatment effect on the treated analysis using counterfactual explanation identifies BMT and SARS-CoV-2 vaccination as protective risk factors associated with COVID-19 severity and survival in patients with multiple myeloma

Patients with multiple myeloma (MM), an age-dependent neoplasm of antibody-producing plasma cells, have compromised immune systems and might be at increased risk for severe COVID-19 outcomes. This study characterizes risk factors associated with clinical indicators of COVID-19 severity and all-cause mortality in myeloma patients utilizing NCATS National COVID Cohort Collaborative (N3C) database. The N3C consortium is a large, centralized data resource representing the largest multi-center cohort of COVID-19 cases and controls nationwide (>16 million total patients, and >6 million confirmed COVID-19+ cases to date). Our cohort included myeloma patients (both inpatients and outpatients) within the N3C consortium who have been diagnosed with COVID-19 based on positive PCR or antigen tests or ICD-10-CM diagnosis code. The outcomes of interest include all-cause mortality (including discharge to hospice) during the index encounter and clinical indicators of severity (i.e., hospitalization/emergency department/ED visit, use of mechanical ventilation, or extracorporeal membrane oxygenation (ECMO)). Finally, causal inference analysis was performed using the propensity score matching (PSM) method. As of 05/16/2022, the N3C consortium included 1,061,748 cancer patients, out of which 26,064 were MM patients (8,588 were COVID-19 positive). The mean age at COVID-19 diagnosis was 65.89 years, 46.8% were females, and 20.2% were of black race. 4.47% of patients died within 30 days of COVID-19 hospitalization. Overall, the survival probability was 90.7% across the course of the study. Multivariate logistic regression analysis showed histories of pulmonary and renal disease, dexamethasone, proteasome inhibitor/PI, immunomodulatory/IMiD therapies, and severe Charlson Comorbidity Index/CCI were significantly associated with higher risks of severe COVID-19 outcomes. Protective associations were observed with blood-or-marrow transplant/BMT and COVID-19 vaccination. Further, multivariate cox proportional hazard analysis showed that high and moderate CCI levels, International Staging System (ISS) moderate or severe stage, and PI therapy were associated with worse survival, while BMT and COVID-19 vaccination were associated with lower risk of death. Finally, matched sample average treatment effect on the treated (SATT) confirmed the causal effect of BMT and vaccination status as top protective factors associated with COVID-19 risk among US patients suffering from multiple myeloma. To the best of our knowledge, this is the largest nationwide study on myeloma patients with COVID-19.

The design of fluorescein-ferrocene derivatives as HOCl-triggered turn-on fluorescent probes and anticancer prodrugs.

Overexpressed HOCl in tumors can behave as an activator for imaging-guided precision therapy. Herein, a new kind of HOCl-activated molecular platform has been developed aiming at the integration of detection, imaging, and anticancer functions. The design strategy uses a five-membered heterocyclic ring to bridge the fluorescent fluorescein part (FL) and the anticancer ferrocene part (Fc). Three derivatives, namely FL-Fc, FL-NP-Fc and FL-TEG-Fc, were designed with different grafted chains on the fluorescein mother to modulate the hydrophilic and biocompatible capacity. In these molecular platforms, the ferrocene unit serves as the fluorescence emission quencher and masked prodrug. These three could respond to HOCl with good selectivity and sensitivity, showing a turn-on fluorescence signal and anticancer efficacy. FL-TEG-Fc with the highest sensitivity (6.5 × 10-6 M) was successfully used for imaging endogenous HOCl in AGS cells, in which it presented strong toxicity IC50 = 9.5 ± 0.3 µM. The mechanistic study revealed that the five-membered heterocyclic ring of FL-TEG-Fc was broken specifically and effectively by HOCl to release strongly fluorescent fluorescein and a bioactive ferrocene derivative; the obtained ferrocene derivative further generated cytotoxic ˙OH through a Fenton-like reaction. This study provides a potential theranostic strategy against HOCl-overexpressing cancers.

Exogenous spermidine enhances the photosynthetic and antioxidant capacity of citrus seedlings under high temperature.

Studies have not fully explained the underlying mechanism of spermidine-mediated heat tolerance. This study investigated the possible role of spermidine (Spd) in regulating citrus heat tolerance. The results showed that exogenous Spd effectively alleviated the limitation of high temperature (HT) on photosynthesis. Exogenous Spd increased the chlorophyll content, net photosynthetic rate, intercellular carbon dioxide concentration, stomatal conductance, maximum and effective quantum yield of PSII photochemistry, nonphotochemical quenching coefficient, and electron transport rate in citrus seedlings under HT stress, but declined the stomatal limitation value. In addition, Spd treatment promoted the dynamic balance of the citrus enzymatic and non-enzymatic antioxidants system. Spd application significantly increased the activity of superoxide dismutase, peroxidase, catalase, ascorbic acid, and glutathione and the expression level of corresponding genes at high temperature, while reducing the content of H2O2 and malondialdehyde. Therefore, our findings suggested exogenous Spd significantly ameliorated citrus physiological and photosynthetic adaptation under HT stress, thereby providing helpful guidance for citrus cultivation in HT events.