Tandem Mass Tag-Labeled Quantitative Proteome Analyses Identify C1R and A2M as Novel Serum Biomarkers in Pregnant Women with Obstructive Sleep Apnea.

The aim of this study was to identify serum diagnostic biomarkers associated with the severity of obstructive sleep apnea (OSA) during pregnancy. Differentially expressed proteins (DEPs) were identified in the control (C), mild (O), and moderate (MO) OSA groups (n = 3 in each group). Bioinformatics analysis was conducted to identify the underlying functions, pathways, and networks of the proteins. Receiver operating characteristic curves were used to assess the diagnostic value of the identified DEPs. The enzyme-linked immunoassay was performed to detect serum levels of the complement C1r subcomponent (C1R) and alpha-2-macroglobulin (A2M) in 79 pregnant women with OSA (mild OSA [n = 32]; moderate OSA [n = 29], and severe OSA [n = 18]) and 65 healthy pregnant women without OSA. Pearson's correlation analysis was conducted to analyze the correlation between C1R and A2M levels and OSA clinicopathological factors. In total, 141 DEPs, 29 DEPs, and 103 DEPs were identified in the three groups (i.e., the mild OSA vs control group, the moderate OSA vs mild apnea group, and the moderate OSA vs control group, respectively). C1R and A2M were identified as continuously up-regulated proteins, and the levels of C1R and A2M were associated with OSA severity. C1R and A2M were found to be correlated with body mass index, systolic blood pressure, apnea-hypopnea index, oxygen desaturation index, time with saturation below 90%, and lowest SaO2. Adverse maternal and neonatal outcomes were observed in pregnant women with OSA. C1R and A2M have been identified as diagnostic biomarkers and are associated with the severity of OSA during pregnancy.

Effect of Salt Substitution on Cardiovascular Events and Death.

BACKGROUND: Salt substitutes with reduced sodium levels and increased potassium levels have been shown to lower blood pressure, but their effects on cardiovascular and safety outcomes are uncertain. METHODS: We conducted an open-label, cluster-randomized trial involving persons from 600 villages in rural China. The participants had a history of stroke or were 60 years of age or older and had high blood pressure. The villages were randomly assigned in a 1:1 ratio to the intervention group, in which the participants used a salt substitute (75% sodium chloride and 25% potassium chloride by mass), or to the control group, in which the participants continued to use regular salt (100% sodium chloride). The primary outcome was stroke, the secondary outcomes were major adverse cardiovascular events and death from any cause, and the safety outcome was clinical hyperkalemia. RESULTS: A total of 20,995 persons were enrolled in the trial. The mean age of the participants was 65.4 years, and 49.5% were female, 72.6% had a history of stroke, and 88.4% a history of hypertension. The mean duration of follow-up was 4.74 years. The rate of stroke was lower with the salt substitute than with regular salt (29.14 events vs. 33.65 events per 1000 person-years; rate ratio, 0.86; 95% confidence interval [CI], 0.77 to 0.96; P = 0.006), as were the rates of major cardiovascular events (49.09 events vs. 56.29 events per 1000 person-years; rate ratio, 0.87; 95% CI, 0.80 to 0.94; P<0.001) and death (39.28 events vs. 44.61 events per 1000 person-years; rate ratio, 0.88; 95% CI, 0.82 to 0.95; P<0.001). The rate of serious adverse events attributed to hyperkalemia was not significantly higher with the salt substitute than with regular salt (3.35 events vs. 3.30 events per 1000 person-years; rate ratio, 1.04; 95% CI, 0.80 to 1.37; P = 0.76). CONCLUSIONS: Among persons who had a history of stroke or were 60 years of age or older and had high blood pressure, the rates of stroke, major cardiovascular events, and death from any cause were lower with the salt substitute than with regular salt. (Funded by the National Health and Medical Research Council of Australia; SSaSS ClinicalTrials.gov number, NCT02092090.).

Simultaneous determination of plasma protein binding of five C-glycosylflavones from TFDS by rapid equilibrium dialysis.

The total flavonoids of Desmodium styracifolium (TFDS) are flavonoid-rich extracts obtained from Desmodii Styracifolii Herba, which is approved for the treatment of urolithiasis in China. C-glycosylflavones including schaftoside, vicenin-1, vicenin-2, vicenin-3, and isovitexin are the main active constituents. In this study, the plasma protein binding of these compounds was determined for the first time in rat and human plasma by rapid equilibrium dialysis combined with HPLC-MS/MS method. The developed method was validated in terms of specificity, linearity, accuracy, precision, extraction effect, matrix effect, and stability. Schaftoside, vicenin-1, vicenin-2, and vicenin-3 exhibited moderate plasma protein binding, ranging from 56.6% to 61.5% in rat plasma and 55.0%-62.9% in human plasma. In comparison, isovitexin demonstrated a higher plasma protein binding in the range of 92.3-93.1% and 95.1-96.2% in rat and human plasma, respectively. Furthermore, the potential interactions mediated via plasma protein binding between isovitexin and nonsteroidal anti-inflammatory drugs (NSAIDs) were investigated by rapid equilibrium dialysis. No significant changes were observed, indicating a lower likelihood of interaction between TFDS and NSAIDs due to plasma protein binding in the treatment of urinary system disorders.

Retrospective evaluation of neonates with fatal congenital lung malformation: A single center 15-year forensic autopsy experience.

Congenital lung malformation (CLM) is a leading cause of infant mortality. Clinical methods for diagnosing CLM mainly rely on computed tomography, magnetic resonance imaging, ultrasonography, and Doppler. However, forensic identification of the cause of death in neonates is challenging. Unequivocal classification criteria for CLM are missing as its forensic identification is ambiguous. Therefore, we aimed to analyze neonatal death cases at our center to assist in identifying those with congenital lung malformation. This retrospective study identified and classified the causes of deaths of neonates autopsied between January 2008 and April 2023. All cases born alive and died within 28 days with a clear time of death were selected, and forensic experts reviewed their records. The manner, cause of death, and other characteristics were noted and discussed. This retrospective study reveals a steady increase in autopsy cases from 2008 to 2015, attributed to improved parental consent, heightened awareness of autopsy importance, and enhanced medical resources. However, a subsequent decline post-2015 is observed, potentially influenced by advancements in medical technology and prenatal examination protocols. The top causes of neonatal mortality include respiratory diseases, asphyxia, congenital dysplasia, and fetal distress. Congenital lung malformations, particularly bronchopulmonary malformations, constitute a significant portion of congenital anomalies. This study underscores the importance of standardized autopsies and histopathological examinations in diagnosing and understanding CLM. Future research should focus on expanding case collections and elucidating the genetic basis of CLM to improve forensic management and outcomes.

Cost-Effectiveness of a Household Salt Substitution Intervention: Findings From 20 995 Participants of the Salt Substitute and Stroke Study.

BACKGROUND: SSaSS (Salt Substitute and Stroke Study), a 5-year cluster randomized controlled trial, demonstrated that replacing regular salt with a reduced-sodium, added-potassium salt substitute reduced the risks of stroke, major adverse cardiovascular events, and premature death among individuals with previous stroke or uncontrolled high blood pressure living in rural China. This study assessed the cost-effectiveness profile of the intervention. METHODS: A within-trial economic evaluation of SSaSS was conducted from the perspective of the health care system and consumers. The primary health outcome assessed was stroke. We also quantified the effect on quality-adjusted life-years (QALYs). Health care costs were identified from participant health insurance records and the literature. All costs (in Chinese yuan [¥]) and QALYs were discounted at 5% per annum. Incremental costs, stroke events averted, and QALYs gained were estimated using bivariate multilevel models. RESULTS: Mean follow-up of the 20 995 participants was 4.7 years. Over this period, replacing regular salt with salt substitute reduced the risk of stroke by 14% (rate ratio, 0.86 [95% CI, 0.77-0.96]; P=0.006), and the salt substitute group had on average 0.054 more QALYs per person. The average costs (¥1538 for the intervention group and ¥1649 for the control group) were lower in the salt substitute group (¥110 less). The intervention was dominant (better outcomes at lower cost) for prevention of stroke as well as for QALYs gained. Sensitivity analyses showed that these conclusions were robust, except when the price of salt substitute was increased to the median and highest market prices identified in China. The salt substitute intervention had a 95.0% probability of being cost-saving and a >99.9% probability of being cost-effective. CONCLUSIONS: Replacing regular salt with salt substitute was a cost-saving intervention for the prevention of stroke and improvement of quality of life among SSaSS participants.

Cu-Catalyzed Regioselective C-H Amination of 2H-Indazoles for the Synthesis of Indazole-Containing Indazol-3(2H)-ones.

A copper-catalyzed C3 amination of 2H-indazoles with 2H-indazoles and indazol-3(2H)-ones under mild conditions was developed. A series of indazole-containing indazol-3(2H)-one derivatives were produced in moderate to excellent yields. The mechanistic studies suggest that the reactions probably proceed through a radical pathway.

Structural Characterization and Effects on Insulin Resistance of a Novel Chondroitin Sulfate from Halaelurus burgeri Skin.

Several studies have isolated chondroitin sulphate (CHS) from sharks' jaws or cartilage. However, there has been little research on CHS from shark skin. In the present study, we extracted a novel CHS from Halaelurus burgeri skin, which has a novel chemical structure and bioactivity on improvement in insulin resistance. Results using Fourier transform-infrared spectroscopy (FT-IR), 1H-nuclear magnetic resonance spectroscopy (1H-NMR), and methylation analysis showed that the structure of the CHS was [4)-ß-D-GlcpA-(1→3)-ß-D-GlcpNAc-(1→]n with 17.40% of sulfate group concentration. Its molecular weight was 238.35 kDa, and the yield was 17.81%. Experiments on animals showed that this CHS could dramatically decrease body weight, reduce blood glucose and insulin levels, lower lipid concentrations both in the serum and the liver, improve glucose tolerance and insulin sensitivity, and regulate serum-inflammatory factors. These results demonstrated that the CHS from H. burgeri skin has a positive effect in reducing insulin resistance because of its novel structure, which provides a significant implication for the polysaccharide as a functional food.

Closure timing of a temporary ileostomy in patients with rectal cancer undergoing anus-preserving operation: a retrospective cohort study.

PURPOSE: To investigate the optimal closure time of a temporary ileostomy in patients with rectal cancer receiving anus-preserving operation. METHODS: Patients with rectal cancer were enrolled from the Affiliated Hospital of Jiangsu University from May 2010 to June 2019. The eligible patients were grouped according to their actual ileostomy closure time after stoma creation. Outcomes were complications during stoma closure and complications within one year after stoma closure. RESULTS: This study included 361 qualified subjects, with 108 patients in the 3-5 months group, 133 in the 5-7 months group and 120 in the ≥ 7 months group. Compared with the risk of complications during stoma closure in the 3-5 months group, that in the 5-7 months group was significantly reduced (odds ratio [OR]: 0.36, 95% confidence interval [CI] 0.13-0.99), and that in the ≥ 7 months group was significantly increased (OR: 5.88, 95% CI 2.38-14.56). In contrast to the 3-5 months group, the 5-7 months group showed a significantly decreased risk (OR: 0.21, 95% CI 0.07-0.67), and the ≥ 7 months group showed a significantly increased risk (OR: 4.21, 95% CI 1.61-11.01) of complications within 1 year after stoma closure. CONCLUSION: 5-7 months after the ileostomy is created may be the optimal time for its closure.

Anti-Obesity and Gut Microbiota Regulation Effects of Phospholipids from the Eggs of Crab, Portunus Trituberculatus, in High Fat Diet-Fed Mice.

There are resourceful phospholipids in the eggs of the crab, Portunus trituberculatus (Pt-PL). However, their components and bioactivities regarding obesity were unclear. Here, we investigated the composition of Pt-PL and their fatty acids. Moreover, its effects on obesity and gut microbiota were also evaluated in high fat diet (HFD)-fed mice. The results showed that Pt-PL contained 12 kinds of phospholipids, mainly including phosphatidylcholine (PC, 32.28%), phosphatidylserine (PS, 26.51%), phosphatidic acid (PA, 19.61%), phosphatidylethanolamine (PE, 8.81%), and phosphatidylinositol (PI, 7.96%). Polyunsaturated fatty acids (PUFAs) predominated in the fatty acids components of Pt-PL, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Animal experiments demonstrated that Pt-PL significantly alleviated body weight gain, adipose gain, hepatic gain, fasting blood glucose, serum insulin, lipid levels in serum and the liver, and systematic inflammation in HFD-fed mice. Furthermore, Pt-PL regulated gut microbiota, especially in a dramatic reduction in the ratio of Firmicutes to Bacteroidetes at phylum level, as well as significant amelioration in their subordinate categories. Pt-PL reduced fecal lipopolysaccharide and total bile acids, and elevated fecal short chain fatty acid (SCFA) concentrations, particularly acetate and butyrate. These findings suggest that Pt-PL possesses anti-obesity effects and can alter gut microbiota owing to the abundance of PUFAs. Therefore, Pt-PL may be developed as an effective food supplement for anti-obesity and regulation of human gut health.

Protocol for a randomized controlled trial to test the acceptability and adherence to 6-months of walnut supplementation in Chinese adults at high risk of cardiovascular disease.

BACKGROUND: Consumption of nuts improves cardio-metabolic risk factors in clinical trials and relates to lower risk of cardiovascular disease (CVD) in prospective observational studies. However, there has not been an adequately powered randomized controlled trial to test if nuts supplementation actually reduces incident CVD. In order to establish the feasibility of such a trial, the current study aimed to assess the acceptability and adherence to long-term nut supplementation amongst individuals at high CVD risk in China. METHODS: This protocol described a 6-month trial performed in Ningxia Province in China among participants with a history of CVD or older age (female ≥65 years, male ≥60 years) with multiple CVD risk factors. Participants were randomized to control (received non-edible gift), low dose walnut (30 g/d), or high dose walnut (60 g/d) groups in a 1:1:1 ratio. Walnuts were provided at no cost to participants and could be consumed according to personal preferences. Follow-up visits were scheduled at 2 weeks, 3 months and 6 months. The primary outcome was fasting plasma alpha linolenic acid (ALA) levels used as an indicator of walnut consumption. Secondary outcomes included self-reported walnut intake from the 24 h dietary recalls. The target sample size of 210 provided 90% statistical power with two-sided alpha of 0.05 to detect a mean difference of 0.12% (as percent of total fatty acid) in plasma ALA between randomized groups. RESULTS: Two hundred and ten participants were recruited and randomized during October 2019. Mean age of participants was 65 years (SD = 7.3), 47% were females, and 94% had a history of CVD at baseline. Across the three study groups, participants had similar baseline demographic and clinical characteristics. DISCUSSION: This trial will quantify acceptability and adherence to long-term walnut supplementation in a Chinese population at high risk of CVD. The findings will support the design of a future large trial to test the effect of walnut supplementation for CVD prevention. TRIAL REGISTRATION: NCT04037943 Protocol version: v3.0 August 14 2019.

Interim effects of salt substitution on urinary electrolytes and blood pressure in the China Salt Substitute and Stroke Study (SSaSS).

The Salt Substitute and Stroke Study is an ongoing 5-year large-scale cluster randomized trial investigating the effects of potassium-enriched salt substitute compared to usual salt on the risk of stroke. The study involves 600 villages and 20,996 individuals in rural China. Intermediate risk markers were measured in a random subsample of villages every 12 months over 3 years to track progress against key assumptions underlying study design. Measures of 24-hour urinary sodium, 24-hour urinary potassium, blood pressure and participants' use of salt substitute were recorded, with differences between intervention and control groups estimated using generalized linear mixed models. The primary outcome of annual event rate in the two groups combined was determined by dividing confirmed fatal and non-fatal strokes by total follow-up time in the first 2 years. The mean differences (95% CI) were -0.32 g (-0.68 to 0.05) for 24-hour urinary sodium, +0.77 g (+0.60 to +0.93) for 24-hour urinary potassium, -2.65 mmHg (-4.32 to -0.97) for systolic blood pressure and +0.30 mmHg (-0.72 to +1.32) for diastolic blood pressure. Use of salt substitute was reported by 97.5% in the intervention group versus 4.2% in the control group (P<.0001). The overall estimated annual event rate for fatal and non-fatal stroke was 3.2%. The systolic blood pressure difference and the annual stroke rate were both in line with the statistical assumptions underlying study design. The trial should be well placed to address the primary hypothesis at completion of follow-up.

Synapse impairment associated with enhanced apoptosis in post-traumatic stress disorder.

Synapse impairment is associated with post-traumatic stress disorder (PTSD), which is characterized by enhanced apoptosis in the hippocampus, amygdala, and other brain regions. However, there are no detailed studies on the relationship between apoptosis and synaptic connectivity in PTSD. In this review, we discuss results from various studies describing the synaptic changes observed in the PTSD brain. A decreased number of dendrites/spines or increased number of immature spines in the hippocampus, medial prefrontal cortex, and other brain regions has been reported. Studies on axon guidance, myelination, and the cytoskeleton suggest that PTSD may involve axon overgrowth and overbranching. Apoptosis affects synapse formation; low levels of caspase maintain the balance between growth cone attraction and repulsion and inhibit axon elongation. PTSD enhances neuronal apoptosis through caspase activation, which disrupts the balance between growth cone attraction and repulsion and alters growth cone trajectory, leading to axon mistargeting. Meanwhile, caspase activation induces dendritic pruning and dendrite degeneration. These events contribute to the formation of fewer and aberrant synapses, which is associated with enhanced apoptosis in PTSD.

Propofol Improves Sensitivity of Lung Cancer Cells to Cisplatin and Its Mechanism.

BACKGROUND Cisplatin (cis-diamminedichloroplatinum, DDP) resistance is identified as the primary obstacle during lung cancer treatment, while DDP resistance is exist extensively. This report was to investigate the roles of propofol in lung cancer cells tolerance to DDP and the potential mechanisms. MATERIAL AND METHODS A549 and A549/DDP cells were treated with DDP for 48 hours, and cell proliferation suppression rate was detected by MTT (thiazolyl blue tetrazolium bromide) assay and half maximal inhibitory concentration (IC50) of DDP to lung cancer cells was calculated. Besides, cell proliferation and apoptosis were determined by MTT assay and flow cytometry assay respectively in propofol-treated A549/DDP and A549 cells. Furthermore, we performed MTT assay to determine the influence of propofol on the sensitivity of lung cancer cells to DDP. RESULTS The results demonstrated that the IC50 of DDP to A549 cells was lower than that in A549/DDP cells. Propofol dramatically inhibited cell proliferation and promoted cell apoptosis of A549/DDP and A549 cells. In addition, propofol significantly improved the anti-proliferative impact of DDP in A549/DDP and A549 cells, and the value of IC50 for DDP in the A549/DDP and A549 cells were decreased after propofol treatment compare to the control group. Moreover, propofol inhibited the Wnt/ß-catenin pathway in a dose-dependent manner in both A549/DDP and A549 cells. CONCLUSIONS Our report indicated that propofol could control lung cancer cell proliferation and apoptosis, and stimulated the suppression function of DDP on lung cancer cell multiplication via the Wnt/ß-catenin signaling pathway, and also provided a new treatment for DDP tolerance to cure lung cancer in clinical.

Identification of Biomarkers for Osteosarcoma Based on Integration Strategy.

BACKGROUND Osteosarcoma (OS) is the most common primary malignant tumor of bone. The identification of novel biomarkers is necessary for the diagnosis and treatment of osteosarcoma. MATERIAL AND METHODS We obtained 11 paired fresh-frozen OS samples and normal controls from patients between September 2015 and February 2017. We used an integration strategy that analyzes next-generation sequencing data by bioinformatics methods based on the pathogenesis of osteosarcoma. RESULTS One susceptibility lncRNA and 7 susceptibility genes regulated by the lncRNA for osteosarcoma were effectively identified, and real-time PCR and clinical index ALP data were used to test their effectiveness. CONCLUSIONS The results showed that the expression levels of the 7 genes were highly consistent in the training and test sample sets, especially between the expression value of the gene ALPL and the plasma detection value of its encoded protein ALP. In particular, both the expression of gene ALPL and the plasma detection values of protein ALP encoded by gene ALPL showed a high degree of consistency among different data types. The identified lncRNA and genes effectively classified the samples proved so that they could be used as potential biomarkers of osteosarcoma. Our strategy may also be helpful for the identification of biomarkers for other diseases.

Falls prevention interventions for community-dwelling older people living in mainland China: a narrative systematic review.

BACKGROUND: Falls in community-dwelling older people have been recognised as a significant public health issue in China given the rapidly growing aged population. Although there are several reviews documenting falls prevention programs for community-dwelling older adults, no systematic reviews of the scope and quality of falls prevention interventions in Mainland China exist. Therefore, the aim of this study was to systematically review falls prevention interventions for community-dwelling older people living in Mainland China. METHODS: We systematically reviewed literature from Chinese and English databases. All types of randomised controlled trials (RCTs) and quasi-experimental studies published from 1st January 1990 to 30th September 2019 were included. Observational studies and studies in care facilities and hospitals were excluded. Narrative synthesis was performed to summarise the key features of all included studies. Quality assessment was conducted using the Cochrane Risk of Bias Tool and ROBINS-I tool for randomised and non-randomised studies respectively. RESULTS: A total of 1020 studies were found, and 101 studies were included in the analysis. Overall, very few high quality studies were identified, and there was insufficient rigor to generate reliable evidence on the effectiveness of interventions or their scalability. Most interventions were multiple component interventions, and most studies focused on outcomes such as self-reported falls incidence or awareness of falls prevention. CONCLUSION: There is an opportunity to undertake an evaluation of a rigorously-designed, large-scale falls prevention program for community-dwelling older people in Mainland China. To help mitigate the rising burden of falls in Mainland China, recommendations for future falls prevention interventions have been made. These include: (1) target disadvantaged populations; (2) incorporate personalised interventions; and (3) investigate the effectiveness of those under-explored interventions, such as psychological, social environment, management of urinary incontinence, fluid or nutrition therapy and surgery. The study results will also potentially provide a useful evidence base for other low-and-middle income countries in a similar situation.

Incidence, risk factors and economic burden of fall-related injuries in older Chinese people: a systematic review.

OBJECTIVE: China's population is ageing and fall-related injury in older Chinese people is a growing public health concern. This review aims to synthesise existing evidence on the incidence, risk factors and economic burden of fall-related injury among older Chinese people to inform health service planning. METHODS: A systematic search of literature on falls and injury among older people living in China was performed in six electronic databases including both English and Chinese databases. Results were combined using narrative synthesis due to the heterogeneity of included studies. RESULTS: A total of 93 studies from Mainland China, Taiwan and Hong Kong were included in this review. Most of these studies were descriptive; 82 reported the incidence of fall-related injury among older Chinese people, 7 studies examined the risk factors for fall-related injury and 22 studies described the economic burden of fall-related injury. The incidence of fall-related injury reported among older Chinese people ranged from 0.6% to 19.5%. Risk factors significantly associated with fall-related injury among older Chinese included older age, female sex, walking aid use, living environments, chronic disease, medication usage, visual impairment and a fall direction other than forward. The cost of fall-related injury among older Chinese people ranged from US$16 to US$3812 per person per fall. CONCLUSION: Falls-related injuries are a significant public health issue for older Chinese people. Further studies using prospective design to identify risk factors and the economic burden of fall-related injuries are needed.

Topical 1% propranolol cream promotes cutaneous wound healing in spontaneously diabetic mice.

Diabetic foot ulcers (DFUs) are a constant threat to diabetic patients and can lead to amputations and even death. Intralesional administration of propranolol in diabetic wounds has not been reported previously. This study aimed to investigate the efficacy of propranolol cream in diabetic wounds. Fifty-six spontaneously diabetic mice were divided into the propranolol group and the control group. After preparing full-thickness wounds on the back of the mice, 1% propranolol cream was topically applied to wounds in the experimental group and 0% propranolol cream in controls. The wound sizes were measured and calculated against the original area. The wounds were analyzed up to 21 days after injury. At all evaluation time-points, the wound size (%) in the propranolol group was significantly smaller than in the controls. Epidermal growth factor (EGF) protein expression increased in the experimental vs. CONTROL GROUP: Vascular endothelial growth factor (VEGF) expression was significantly lower in the experimental vs. control group whereas NG2 proteoglycan was increased throughout the study. However, matrix metallopeptidase (MMP)-9 expression was at first significantly higher in the experimental vs. control group then the MMP-9 protein level in the control group increased and surpassed that in the experimental group. In conclusion, intralesional administration of 1% propranolol cream promotes reepithelialization and regulates abnormal angiogenesis in diabetic wounds. Propranolol cream may become a new drug for the treatment of DFUs.

Norepinephrine Regulates Keratinocyte Proliferation to Promote the Growth of Hair Follicles.

Psychological factors and stress can cause hair loss. The sympathetic-adrenal-medullary (SAM) axis has been reported to regulate the growth of hair follicles (HF). The sympathetic nerve is a component of the SAM axis, but it has not been sufficiently or convincingly linked to hair growth. In this study, we demonstrate that chemical sympathectomy via administration of the neurotoxin 6-hydroxydopamine (6-OHDA) to mice inhibited HF growth, but treatment with the ß-adrenoceptor antagonist propranolol (PR) had no effect. HF length and skin thickness were greater in PR-treated and control mice than in 6-OHDA-treated mice, as evidenced by hematoxylin and eosin staining. Furthermore, we found that the reduced HF growth in sympathectomized animals was accompanied by a decreased keratinocyte proliferation. Moreover, the neurotransmitter norepinephrine (NE) was found to efficiently promote HF growth in an organotypic skin culture model. Together, these findings suggest that sympathetic nerves regulate keratinocyte behaviors to promote hair growth, providing novel insights into stress-related, chemotherapy-, and radiotherapy-induced alopecia.

TCMNPAS: a comprehensive analysis platform integrating network formulaology and network pharmacology for exploring traditional Chinese medicine.

The application of network formulaology and network pharmacology has significantly advanced the scientific understanding of traditional Chinese medicine (TCM) treatment mechanisms in disease. The field of herbal biology is experiencing a surge in data generation. However, researchers are encountering challenges due to the fragmented nature of the data and the reliance on programming tools for data analysis. We have developed TCMNPAS, a comprehensive analysis platform that integrates network formularology and network pharmacology. This platform is designed to investigate in-depth the compatibility characteristics of TCM formulas and their potential molecular mechanisms. TCMNPAS incorporates multiple resources and offers a range of functions designed for automated analysis implementation, including prescription mining, molecular docking, network pharmacology analysis, and visualization. These functions enable researchers to analyze and obtain core herbs and core formulas from herbal prescription data through prescription mining. Additionally, TCMNPAS facilitates virtual screening of active compounds in TCM and its formulas through batch molecular docking, allowing for the rapid construction and analysis of networks associated with "herb-compound-target-pathway" and disease targets. Built upon the integrated analysis concept of network formulaology and network pharmacology, TCMNPAS enables quick point-and-click completion of network-based association analysis, spanning from core formula mining from clinical data to the exploration of therapeutic targets for disease treatment. TCMNPAS serves as a powerful platform for uncovering the combinatorial rules and mechanism of TCM formulas holistically. We distribute TCMNPAS within an open-source R package at GitHub ( https://github.com/yangpluszhu/tcmnpas ), and the project is freely available at http://54.223.75.62:3838/ .

MRS study on the correlation between frontal GABA+/Glx ratio and abnormal cognitive function in medication-naive patients with narcolepsy.

OBJECTIVE: To compare the GABA+/Glx (glutamate-glutamine) ratio in the prefrontal lobe under non-rapid eye movement sleep between patients with narcolepsy type 1 (NT1) and normal controls and explore the correlation between this difference and abnormal cognitive function, using synchronous electroencephalography-functional magnetic resonance spectroscopy (EEG-fMRS). METHODS: MRS measurements of GABA+ and Glx concentrations as well as synchronous EEG data were obtained from 26 medication-naive patients with NT1 and 29 sex- and age-matched healthy community volunteers. Cognition was appraised with the Beijing version of the Montreal Cognitive Assessment, and daytime sleepiness was measured using the Epworth Sleepiness Scale. All subjects recorded a 2-week sleep log as well as an overnight polysomnography within 1 week before MR scanning to understand their sleep habits and determine sleep stages. After PSG, they also underwent multiple sleep latency trials. Patient/control group differences in the individual measurements of GABA+ and Glx and the GABA+/Glx ratio and their relationship with cognition were assessed. RESULTS: The GABA+/Glx ratio and GABA + levels of patients with narcolepsy were higher than those of the control group (P＜0.0001 and P = 0.0008, respectively). However, there was no significant difference in Glx levels (P = 0.6360). The GABA+/Glx ratio negatively correlated with abnormal cognitive function (r = -0.6710, P = 0.0002). Moreover, GABA + levels were inversely proportional to rapid eye movement sleep latency (REML) in patients with narcolepsy (r = -0.5019, P = 0.0106). CONCLUSION: The GABA+/Glx ratio in the prefrontal lobe was higher in NT1 patients during N2 sleep than in normal controls, mainly caused by GABA + levels; this ratio was negatively related to abnormal cognitive function. In addition, GABA + levels were inversely proportional to REML.