Proteomic and antimicrobial peptide analyses of Buffalo colostrum and mature Milk whey: A comparative study.

Buffalo colostrum is the initial mammary secretion after parturition, consisting of nutritional and bioactive components. In this study, we conducted a proteomic analysis of buffalo colostrum whey to identify bioactive proteins and peptides. A total of 107 differentially expressed proteins (DEPs) were identified in buffalo colostrum whey compared to those in mature milk. Gene Ontology analysis revealed that DEPs were primarily associated with immune response and tissue development. KEGG pathway enrichment suggested that colostrum actively enhances nascent immunity involved in interleukin and interferon signaling pathways. Furthermore, candidate antimicrobial peptides (AMPs) of whey protein hydrolysates from buffalo colostrum were characterized, which exhibits broad-spectrum activity against gram-positive and gram-negative pathogens. Overall, this study improves our understanding of protein variations in buffalo lactation, and contributes to the development of AMPs from buffalo colostrum.

Efficacy and safety of neoadjuvant sintilimab in combination with FLOT chemotherapy in patients with HER2-negative locally advanced gastric or gastroesophageal junction adenocarcinoma: an investigator-initiated, single-arm, open-label, phase II study.

BACKGROUND: The addition of immune checkpoint inhibitors to neoadjuvant chemotherapy in operable advanced gastric or gastroesophageal junction (G/GEJ) cancer aroused wide interest. This study was designed to assess the efficacy and safety of neoadjuvant sintilimab, a programmed cell death protein-1 (PD-1) inhibitor, in combination with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy for HER2-negative locally advanced G/GEJ cancer. METHODS: Eligible patients with clinical stage cT4 and/or cN+M0 G/GEJ cancer were enroled in this phase II study. Patients received neoadjuvant sintilimab (200 mg every 3 weeks) for three cycles plus FLOT (50 mg/m 2 docetaxel, 80 mg/m 2 oxaliplatin, 200 mg/m 2 calcium levofolinate, 2600 mg/m 2 5-fluorouracil every 2 weeks) for four cycles before surgery, followed by four cycles of adjuvant FLOT with same dosages after resection. The primary endpoint was the pathological complete response (pCR) rate. RESULTS: Thirty-two patients were enroled between August 2019 and September 2021, with a median follow-up of 34.8 (95% CI, 32.8-42.9) months. Thirty-two (100%) patients received neoadjuvant therapy, and 29 underwent surgery with an R0 resection rate of 93.1%. The pCR (TRG0) was achieved in 5 (17.2%; 95% CI, 5.8-35.8%) patients, and the major pathological response was 55.2%. Twenty-three (79.3%) patients had T downstaging, 21 (72.4%) had N downstaging, and 19 (65.5%) had overall TNM downstaging. Six (20.7%) patients experienced recurrence. Patients achieving pCR showed better event-free survival (EFS), disease-free survival (DFS), and overall survival (OS) than non-pCR. The estimated 3-year EFS rate, 3-year DFS rate, and 3-year OS rate were 71.4% (95% CI, 57.2-89.2%), 78.8% (95% CI, 65.1-95.5%), and 70.9% (95% CI, 54.8-91.6%), respectively. The objective response rate and disease control rate were 84.4% (95% CI, 68.3-93.1%) and 96.9% (95% CI, 84.3-99.5%), respectively. Twenty-five (86.2%) received adjuvant therapy. The main grade ≥3 treatment-related adverse events (TRAEs) were lymphopenia (34.4%), neutropenia (28.1%), and leukopenia (15.6%). no patients died from TRAE. The LDH level exhibited a better predictive value to pathological responses than PD-L1 and MSI status. CONCLUSIONS: The study demonstrated an encouraging efficacy and manageable safety profile of neoadjuvant sintilimab plus FLOT in HER2-negative locally advanced G/GEJ cancer, which suggested a potential therapeutic option for this population.

Acupuncture for primary insomnia: Effectiveness, safety, mechanisms and recommendations for clinical practice.

Primary insomnia (PI) is an increasing concern in modern society. Cognitive-behavioral therapy for insomnia is the first-line recommendation, yet limited availability and cost impede its widespread use. While hypnotics are frequently used, balancing their benefits against the risk of adverse events poses challenges. This review summarizes the clinical and preclinical evidence of acupuncture as a treatment for PI, discussing its potential mechanisms and role in reliving insomnia. Clinical trials show that acupuncture improves subjective sleep quality, fatigue, cognitive impairments, and emotional symptoms with minimal adverse events. It also positively impacts objective sleep processes, including prolonging total sleep time, improving sleep efficiency, reducing sleep onset latency and wake after sleep onset, and enhancing sleep architecture/structure, including increasing N3% and REM%, and decreasing N1%. However, methodological shortcomings in some trials diminish the overall quality of evidence. Animal studies suggest that acupuncture restores circadian rhythms in sleep-deprived rodents and improves their performance in behavioral tests, possibly mediated by various clinical variables and pathways. These may involve neurotransmitters, brain-derived neurotrophic factors, inflammatory cytokines, the hypothalamic-pituitary-adrenal axis, gut microbiota, and other cellular events. While the existing findings support acupuncture as a promising therapeutic strategy for PI, additional high-quality trials are required to validate its benefits.

Identifying complementary and alternative medicine recommendations for anxiety treatment and care: a systematic review and critical assessment of comprehensive clinical practice guidelines.

Background: Clinical practice guidelines (CPGs) are used to guide decision-making, especially regarding complementary and alternative medicine (CAM) therapies that are unfamiliar to orthodox healthcare providers. This systematic review aimed to critically review and summarise CAM recommendations associated with anxiety management included in the existing CPGs. Methods: Seven databases, websites of six international guidelines developing institutions, and the National Centre for Complementary and Integrative Health website were systematically searched. Their reporting and methodological quality were evaluated using the Reporting Items for practice Guidelines in Healthcare checklist and the Appraisal of Guidelines for Research and Evaluation (2nd version) instrument, respectively. Results: Ten CPGs were included, with reporting rates between 51.4 and 88.6%. Seven of these were of moderate to high methodological quality. Seventeen CAM modalities were implicated, involving phytotherapeutics, mind-body practice, art therapy, and homeopathy. Applied relaxation was included in 70% CPGs, which varied in degree of support for its use in the treatment of generalised anxiety disorder. There were few recommendations for other therapies/products. Light therapy was not recommended for use in generalised anxiety disorder, and St John's wort and mindfulness were not recommended for use in social anxiety disorder in individual guidelines. Recommendations for the applicability of other therapies/products for treating a specific anxiety disorder were commonly graded as "unclear, unambiguous, or uncertain". No CAM recommendations were provided for separation anxiety disorder, specific phobia or selective mutism. Conclusion: Available guidelines are limited in providing logically explained graded CAM recommendations for anxiety treatment and care. A lack of high-quality evidence and multidisciplinary consultation during the guideline development are two major reasons. High quality and reliable clinical evidence and the engagement of a range of interdisciplinary stakeholders are needed for future CPG development and updating. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022373694, identifier CRD42022373694.

Managing depression with complementary and alternative medicine therapies: a scientometric analysis and visualization of research activities.

Background: Complementary and Alternative Medicine (CAM) interventions may prove to be an attractive option for the treatment of depression. The aim of this scientometric analysis is to determine the global scientific output of research regarding managing depression with CAM and identify the hotspots and frontiers within this theme. Methods: Publications regarding the utilization of CAM for treating depression were collected from the Web of Science Core Collection from 1993 to 2022, and analyzed and visualized by Bibliometrix R-package, VOSviewer, and CiteSpace. Results: A total of 1,710 publications were acquired. The number of annual publications showed an overall rapid upward trend, with the figure peaking at 179 in 2021. The USA was the leading research center. Totally 2,323 distinct institutions involving 7,638 scholars contributed to the research theme. However, most of the cooperation was limited to within the same country, institution or research team. The Journal of Alternative and Complementary Medicine was the most productive periodical. The CAM therapies of most interest to researchers were acupuncture and body-mind techniques, such as yoga, meditation and mindfulness. Systematic review and meta-analysis are commonly used methods. "Inflammation," "rating scale" and "psychological stress" were identified as the most studied trend topics recently. Conclusion: Managing depression with evidence-based CAM treatment is gaining attention globally. Body-mind techniques and acupuncture are growing research hotspots or emerging trending topics. Future studies are predicted to potentially investigate the possible mechanisms of action underlying CAM treatments in reducing depression in terms of modulation of psychological stress and inflammation levels. Cross-countries/institutes/team research collaborations should be encouraged and further enhanced.

Identifying complementary and alternative medicine recommendations for insomnia treatment and care: a systematic review and critical assessment of comprehensive clinical practice guidelines.

Background: There is a need for evidence-informed guidance on the use of complementary and alternative medicine (CAM) for insomnia because of its widespread utilization and a lack of guidance on the balance of benefits and harms. This systematic review aimed to identify and summarize the CAM recommendations associated with insomnia treatment and care from existing comprehensive clinical practice guidelines (CPGs). The quality of the eligible guidelines was appraised to assess the credibility of these recommendations. Methods: Formally published CPGs incorporating CAM recommendations for insomnia management were searched for in seven databases from their inception to January 2023. The NCCIH website and six websites of international guideline developing institutions were also retrieved. The methodological and reporting quality of each included guideline was appraised using the AGREE II instrument and RIGHT statement, respectively. Results: Seventeen eligible GCPs were included, and 14 were judged to be of moderate to high methodological and reporting quality. The reporting rate of eligible CPGs ranged from 42.9 to 97.1%. Twenty-two CAM modalities were implicated, involving nutritional or natural products, physical CAM, psychological CAM, homeopathy, aromatherapy, and mindful movements. Recommendations for these modalities were mostly unclear, unambiguous, uncertain, or conflicting. Logically explained graded recommendations supporting the CAM use in the treatment and/or care of insomnia were scarce, with bibliotherapy, Tai Chi, Yoga, and auriculotherapy positively recommended based on little and weak evidence. The only consensus was that four phytotherapeutics including valerian, chamomile, kava, and aromatherapy were not recommended for insomnia management because of risk profile and/or limited benefits. Conclusions: Existing guidelines are generally limited in providing clear, evidence-informed recommendations for the use of CAM therapies for insomnia management due to a lack of high-quality evidence and multidisciplinary consultation in CPG development. More well-designed studies to provide reliable clinical evidence are therefore urgently needed. Allowing the engagement of a range of interdisciplinary stakeholders in future updates of CPGs is also warranted. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=369155, identifier: CRD42022369155.

Potentially migrating and residual components of biochar: Effects on phosphorus adsorption performance and storage capacity of black soil.

Biochar has great potential to increase the soil nutrient storage capacity. However, with aging, biochar gradually disintegrates and releases fractions with migration potential, resulting in unknown effects on soil nutrient regulation. Based on this problem, we used ultrasound to separate original biochar (TB) into potentially migrating biochar (DB) and residual biochar (RB). The elemental composition and pore characteristics of TB, DB and RB were analyzed. Different fractions of biochar were applied to black soil, and the kinetic model and isothermal adsorption models were used to explore the adsorption characteristics of different treatments. Then, the effects of initial pH and coexisting ions on adsorption were compared. The adsorption mechanism and potential leaching process of phosphorus in soil were investigated. The results showed that RB had higher O and H contents and was less stable than TB, while RB was more aromatic. The phosphorus adsorption capacity of different treatments was SRB (1.3318 mg g-1) > STB (1.2873 mg g-1) > SDB (1.3025 mg g-1) > SCK (1.1905 mg g-1). SRB had optimal phosphorus adsorption performance and storage capacity, with a maximum adsorption capacity of 1.6741 mg g-1 for the Langmuir isotherm, and it also showed excellent applicability in a pH gradient and with coexisting ions. The main adsorption mode of phosphorus by different treatments was monolayer chemisorption, related to electrostatic repulsion and oxygen-containing functional groups. DB was less effective in inhibiting soil phosphorus migration, with the cumulative leaching of SDB reaching 8.99 mg and the percentage of phosphorus in the 0-6 cm soil layer reaching only 15.42%. Overall, the results can help elucidate potential trends in the adsorption performance and migration process of soil phosphorus by biochar, and improve the comprehensive utilization efficiency of biochar.

Saikosaponin B2 ameliorates depression-induced microglia activation by inhibiting ferroptosis-mediated neuroinflammation and ER stress.

ETHNOPHARMACOLOGICAL RELEVANCE: Saikosaponins B2 (SSB2) is one of the main active components isolated from Radix Bupleuri (Bupleurum chinense DC.), a herb widely used of traditional Chinese medicine. It has been used for the treatment of depression for more than two thousand years. However, the molecular mechanisms remain to be determined. AIM OF THE STUDY: In this study, we evaluated the anti-inflammatory effect and elucidated underlying molecular mechanisms of SSB2 in LPS-induced primary microglia and CUMS-induced mice model of depression. METHOD: The effects of SSB2 treatment were investigated both in vitro and in vivo. The chronic unpredictable mild stimulation (CUMS) procedure was applied to establish the animal model of depression. Behavioural tests were used to evaluate the depressive-like behaviors in CUMS-exposed mice, including sucrose preference test, open field test, tail suspension test, and forced swimming test. The GPX4 gene of microglia was silenced using shRNA, and inflammatory cytokines were determined by Western Blot and immunofluorescence analysis. Endoplasmic reticulum stress and ferroptosis-related markers were detected by qPCR, flow cytometry and confocal microscopy. RESULT: SSB2 reversed depressive-like behaviours in CUMS-exposed mice and relieved central neuroinflammation and ameliorated hippocampal neural damage. SSB2 alleviated LPS-induced activation of microglia through the TLR4/NF-κB pathway. LPS-induced ferroptosis, with increased levels of ROS, intracellular Fe2+, mitochondrial membrane potential, lipid peroxidation, GSH, SLC7A11, FTH, GPX4 and Nrf2, and decreased transcription levels of ACSL4 and TFR1, was attenuated with SSB2 treatment in primary microglia cells. GPX4 knockdown activated ferroptosis, induced endoplasmic reticulum (ER) stress, and abrogated the protective effects of SSB2. Further, SSB2 attenuated ER stress, balanced calcium homeostasis, reduced lipid peroxidation and intracellular Fe2+ content by regulating the level of intracellular Ca2+. CONCLUSIONS: Our study suggested that SSB2 treatment can inhibit ferroptosis, maintain calcium homeostasis, relieve endoplasmic reticulum stress and attenuate central neuroinflammation. SSB2 exhibited anti-ferroptosis and anti-neuroinflammatory effects through the TLR4/NF-κB pathway in a GPX4-dependent manner.

Efficacy and Safety of 1470 nm Diode Laser Enucleation of the Prostate in Elderly Benign Prostatic Hyperplasia Patients.

Objective: The aim of this study was to evaluate efficacy and safety of 1470 nm diode laser enucleation of the prostate (DiLEP) and plasmakinetic resection of the prostate (PKRP) in elderly benign prostatic hyperplasia (BPH) patients with lower urinary tract symptoms. Methods: A total of 123 elderly patients with BPH were randomized to undergo either 1470 nm DiLEP or PKRP by means of a random number table from September 2020 to April 2022. The perioperative and postoperative data were studied during a 3- and 6-month follow-up. Results: The patients treated with 1470 nm DiLEP had significantly decreased operation time (74.6 ± 17.0 vs 98.8 ± 18.9 minutes, p < 0.001), hemoglobin loss (1.06 ± 0.49 vs 1.59 ± 0.60 g/dL, p < 0.001), bladder irrigation time (22.1 ± 8.1 vs 33.9 ± 10.0 hours, p < 0.001), catheter duration (3.2 ± 1.3 vs 5.8 ± 1.0 days, p < 0.001), and hospital stay (7.6 ± 1.4 vs 9.6 ± 1.3 days, p < 0.001) compared with the PKRP group. Besides, International Index of Erectile Function-5 score of 1470 nm DiLEP group at postoperative 3- and 6-month follow-up was significantly higher than PKRP group. No differences achieving statistical significance were identified in total prostate-specific antigen, maximum urinary flow rate, International Prostate Symptom Score, quality-of-life score, and the postvoid residual urine volume, transient incontinence, urethral stricture, bladder neck contracture, and retrograde ejaculation at 3- and 6-month follow-up. Conclusions: 1470 nm DiLEP is safer than PKRP, with a smaller effect on sexual function, and it is comparable with the efficacy of PKRP, thus making it more suitable for elderly BPH patients. Clinical Trial Registration number: S2021-463-01.

Cyasterone inhibits IL-1ß-mediated apoptosis and inflammation via the NF-κB and MAPK signaling pathways in rat chondrocytes and ameliorates osteoarthritisin vivo.

Osteoarthritis is a prevalent global joint disease, which is characterized by inflammatory reaction and cartilage degradation. Cyasterone, a sterone derived from the roots of Cyathula officinalis Kuan, exerts protective effect against several inflammation-related diseases. However, its effect on osteoarthritis remains unclear. The current study was designed to investigate the potential anti-osteoarthritis activity of cyasterone. Primary chondrocytes isolated from rats induced by interleukin (IL)-1ß and a rat model stimulated by monosodium iodoacetate (MIA) were used for in vitro and in vivo experiments, respectively. The results of in vitro experiments showed that cyasterone apparently counteracted chondrocyte apoptosis, increased the expression of collagen II and aggrecan, and restrained the production of the inflammatory factors inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5), metalloproteinase-3 (MMP-3), and metalloproteinase-13 (MMP-13) induced by IL-1ß in chondrocytes. Furthermore, cyasterone ameliorated the inflammation and degenerative progression of osteoarthritis potentially by regulating the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. For in vivo experiments, cyasterone significantly alleviated the inflammatory response and cartilage destruction of rats induced by monosodium iodoacetate, where dexamethasone was used as the positive control. Overall, this study laid a theoretical foundation for developing cyasterone as an effective agent for the alleviation of osteoarthritis.

Acupuncture for comorbid depression and insomnia in perimenopause: A feasibility patient-assessor-blinded, randomized, and sham-controlled clinical trial.

Background and objective: Whilst acupuncture is widely used for treating psychosomatic diseases, there is little high-quality evidence supporting its application in comorbid perimenopausal depression (PMD) and insomnia (PMI) which are common complaints during climacteric. This feasibility, patient-assessor-blinded, randomized, sham-controlled clinical trial addresses this gap by investigating the efficacy and safety of acupuncture on depressed mood and poor sleep in women with comorbid PMD and PMI. Methods: Seventy eligible participants were randomly assigned to either real-acupuncture (RA) or sham-acupuncture (SA) groups. Either RA or SA treatment were delivered in 17 sessions over 8 weeks. The primary outcomes for mood and sleep were changes on 17-items Hamilton Depression Rating Scale (HAM-D17) and Pittsburgh Sleep Quality Index (PSQI) scores, from baseline to 16-week follow-up. Secondary outcome measures involved anxiety symptoms, perimenopausal symptoms, quality of life, participants' experience of and satisfaction with the acupuncture treatment. Blood samples were taken to measure reproductive hormone levels. Intention-To-Treat and Per-Protocol analyses were conducted with linear mixed-effects models. The James' and Bang's blinding indices were used to assess the adequacy of blinding. Results: Sixty-five participants completed all treatment sessions, and 54 and 41 participants completed the eight- and 16-week follow-ups, respectively. At post-treatment and 8-week follow-up, the RA group showed a significantly greater reduction in PSQI scores than the SA group did; although the reduction of HAM-D17 scores in RA group was significant, the change was not statistically different from that of SA. There were no significant mean differences between baseline and 16-week follow-up in either HAM-D17 or PSQI in either group. There were no significant between-group differences in serum reproductive hormone levels. All treatments were tolerable and no serious adverse events were reported, and the blinding was successful. Conclusion: Acupuncture is safe and can contribute to clinically relevant improvements in comorbid PMD and PMI, with satisfactory short-and medium-term effects. Whether the anti-depressive benefit of acupuncture is specific or non-specific remains to be determined. No evidence was found for any longer-term benefit of acupuncture compared to sham at 16 weeks. Further research is required to elucidate mechanisms underlying the short to medium term effects of acupuncture.

Evaluating the effects of vitamin D Level on airway obstruction in two asthma endotypes in humans and in two mouse models with different intake of vitamin D during early-life.

Introduction: Asthma is primarily divided into two categories: type 2 (T2-high) and non-type 2 (T2-low). A relationship between asthma severity and vitamin D deficiency has been identified, but its impact on each asthma endotype remains unknown. Methods: We clinically examined the influence of vitamin D on patients with T2-high (n = 60) or T2-low asthma (n = 36) compared with controls (n = 40). Serum 25(OH)D levels, inflammatory cytokines and spirometry were measured. Mouse models were then used to further analyze the effects of vitamin D on both asthmatic endotypes. BALB/c mice were fed with vitamin D-deficient (LVD), -sufficient (NVD), or -supplemented diets (HVD) throughout lactation and offspring followed the same diet after weaning. Offspring were sensitized/challenged with ovalbumin (OVA) to establish "T2-high" asthma or OVA combined with ozone exposure (OVA + ozone) to induce "T2-low" asthma. Spirometry and serum, bronchoalveolar lavage fluid (BALF), and lung tissues were analyzed. Results: Serum 25(OH)D levels were decreased in asthmatic patients compared with controls. Patients with vitamin D deficiency (Lo) had varying degrees of elevation of the pro-inflammatory cytokines IL-5, IL-6, and IL-17A, decreased expression of the anti-inflammatory cytokine IL-10, and altered forced expiratory volume in the first second as a percentage of predicted value (FEV1%pred) in both asthmatic endotypes. Vitamin D status had a stronger correlation with FEV1%pred in T2-low asthma than T2-high asthma, and 25(OH)D level was only positively linked to maximal mid-expiratory flow as a percentage of predicted value (MMEF%pred) in the T2-low group. Inflammation, hyperresponsiveness, and airway resistance (RL) was increased in both asthma models compared with controls while vitamin D deficiency further increased airway inflammation and airway obstruction. These findings were particularly prominent in T2-low asthma. Discussion: The potential function and mechanisms of vitamin D and both asthma endotypes should be studied individually, and further analysis of the potential signaling pathways involved with vitamin D on T2-low asthma is warranted.

[Clinical observation of acupuncture at Huiyin (CV 1) for chronic severe functional constipation].

OBJECTIVE: To compare the effect of acupuncture at Huiyin (CV 1) and oral administration of western medication in treatment of chronic severe functional constipation (CSFC). METHODS: A total of 64 patients with CSFC were randomly divided into an acupuncture group (32 cases, 5 cases dropped off) and a western medication group (32 cases, 4 cases dropped off). Both groups were given routine basic treatment. The acupuncture group was treated by directly puncture of 20-30 mm at Huiyin (CV 1), once a day for the first 4 weeks, 5 times a week, once every other day for the next 4 weeks, 3 times a week, totally for 8 weeks. The western medication group was treated with 2 mg prucalopride succinate tablets orally before breakfast every day for 8 weeks. The average number of weekly spontaneous bowel movement (SBM) of the two groups were observed before treatment and 1-8 weeks into treatment. The constipation symptom score before and after treatment, and in follow-up of 1 month after treatment, as well as quality of life [patient assessment of constipation quality of life questionnaire (PAC-QOL) score and the proportion of patients of PAC-QOL score difference before and after treatment≥1] before and after treatment were compared in the two groups. The clinical effects of the two groups were evaluated after treatment and in follow-up. RESULTS: Compared before treatment, the average number of weekly SBM in the two groups was increased 1-8 weeks into treatment (P<0.05). The average number of weekly SBM in the acupuncture group was less than that in the western medication group 1 week into treatment (P<0.05), and the average number of weekly SBM in the observation group was more than that in the western medication group 4-8 weeks into treatment (P<0.05). The scores of constipation symptom after treatment and in follow-up and scores of PAC-QOL after-treatment in the two groups were lower than those before treatment (P<0.05), and those in the acupuncture group were lower than the western medication group (P<0.05). The proportion of patients of PAC-QOL score difference before and after treatment≥1 in the acupuncture group was higher than that in the west medication group (P<0.05). The total effective rates after treatment and in follow-up in the acupuncture group were 81.5% (22/27) and 78.3% (18/23), respectively, which were better than 42.9% (12/28) and 43.5% (10/23) in the western medication group (P<0.05). CONCLUSION: Acupuncture at Huiyin (CV 1) can effectively increase the number of spontaneous defecation in patients with CSFC, reduce constipation symptoms, improve the quality of life, and the effect after treatment and in follow-up is better than oral western medication.

Fermented Gynochthodes officinalis (F.C.How) Razafim. & B.Bremer alleviates diabetic erectile dysfunction by attenuating oxidative stress and regulating PI3K/Akt/eNOS pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: As a traditional Chinese medicine, Gynochthodes officinalis (F.C.How) Razafim. & B.Bremer (G. officinalis) has been historically as tonics to treat impotence. Fermentation is an ancient processing method for traditional Chinese medicine. Whether fermentation affects the therapeutic effects of G. officinalis on diabetic erectile dysfunction has so far remained unknown. AIMS OF THE STUDY: In this research, we aim to determine the effect of fermented or unfermented G. officinalis root extract on diabetes mellitus-induced erectile dysfunction (DMED) and the potential mechanisms. MATERIALS AND METHODS: Candida sp. B5, Lactobacillus sp. Y5 and Lactobacillus sp. R2 are applied for the fermentation of G. officinalis. The optimum fermentation conditions of G. officinalis are investigated. Sprague-Dawley rats were used to establish a diabetic erectile dysfunction model, treated with different concentrations of fermented or unfermented G. officinalis, to compare the effect of fermented or unfermented G. officinalis on DMED and explore underlying mechanisms by assessment of intracavernous pressure, ELISA, Western blot, Masson's trichrome staining, and immunofluorescence. The corpus cavernosum smooth muscle cells (CCSMCs) and Schwann cells were isolated and used to investigate the effect of fermented or unfermented G. officinalis on hydrogen peroxide (H2O2)-induced apoptosis. RESULTS: The results reveal the optimum fermentation conditions of G. officinalis using Lactobacillus sp. Y5 were determined to be 35 °C, the ratio of solid to liquid 1:10, and six days of fermentation. The fermentation increases the abundance of major active ingredients within G. officinalis. After fermented or unfermented G. officinalis treatment for eight weeks by oral gavage at a dose of 100 mg kg-1 or 300 mg kg-1, the results show that the fermentation enhances the effect of G. officinalis on diabetic erectile dysfunction detected by intracavernous pressure. The protein expressions of the PI3K/Akt/eNOS pathway were upregulated in diabetic rats after fermented or unfermented G. officinalis treatment, while the level of oxidative stress was significantly reduced. Meanwhile, Masson's trichrome staining also displayed an improvement in the ratio of smooth muscle to collagen. In vitro experiments confirmed that fermented or unfermented G. officinalis protected CCSMCs and Schwann cells from apoptosis. In contrast, fermented G. officinalis showed a fortified protective effect over unfermented G. officinalis. CONCLUSION: Our findings suggest that fermentation can increase the composition of main active ingredients in G. officinalis and enhance its role in diabetic erectile dysfunction. It augurs the potential therapeutic application of fermented G. officinalis well for treating diabetic erectile dysfunction.

[Discussion on Technical Evaluation of Tongue Diagnosis Equipment of Traditional Chinese Medicine].

This study briefly introduces the tongue diagnostic equipment of traditional Chinese medicine. It analyzes and discusses the key points of technical evaluation of tongue diagnostic equipment from the aspects of product name, performance parameters, image processing functions, product use methods, clinical evaluation, etc. It analyzes the safety risks and effectiveness indicators of tongue diagnostic equipment, hoping to bring some help to the gradual standardization of tongue diagnostic equipment and the registration of enterprises.

Photoallosteric Polymersomes toward On-Demand Drug Delivery and Multimodal Cancer Immunotherapy.

Allosteric transitions can modulate the self-assembly and biological function of proteins. It remains, however, tremendously challenging to design synthetic allosteric polymeric assemblies with spatiotemporally switchable hierarchical structures and functionalities. Here, a photoallosteric polymersome is constructed that undergoes a rapid conformational transition from ß-sheet to α-helix upon exposure to near-infrared light irradiation. In addition to improving nanoparticle cell penetration and lysosome escape, photoinduced allosteric behavior reconstructs the vesicular membrane structure, which stimulates the release of hydrophilic cytolytic peptide melittin and hydrophobic kinase inhibitor sorafenib. Combining on-demand delivery of multiple therapeutics with phototherapy results in apoptosis and immunogenic death of tumor cells, remold the immune microenvironment and achieve an excellent synergistic anticancer efficacy in vivo without tumor recurrence and metastasis. Such a light-modulated allosteric transition in non-photosensitive polymers provides new insight into the development of smart nanomaterials for biosensing and drug delivery applications.

Effect of combined aging treatment on biochar adsorption and speciation distribution for Cd(II).

As a passivation material for heavy metals in-situ remediation, biochar (BC) has often been expected to maintain long-term adsorption performance for target pollutants. There is still lack of consensus about the impact of aging processes on biochar properties, particularly with respect to its long-term sorption performance. In this study, the changes to immobilization mechanisms as well as the speciation distribution of Cd(II) triggered by combined aging simulation (dry-wet, freeze-thaw cycle and oxidation treatment) on BC prepared under three levels of pyrolysis temperatures (300, 500 and 700 °C) were investigated. The results showed significant inhibition of aging on adsorption performance with the adsorptive capacity of BC300, BC500 and BC700 for Cd(II) decreased by 31.12 %, 50.63 % and 14.94 %, respectively. However, sequential extraction results indicated little influence of the aging process on the relative fractionation of Cd(II) speciation. The distribution of readily bioavailable, potentially bioavailable and non-bioavailable fractions of Cd(II) on BC showed only minimal changes post-aging. Overall, there was less Cd(II) sorption following aging, but the fractional availability (in relative terms) remained the same. Compared with 300 and 700 °C, the biochar prepared under 500 °C accounted the highest fraction of non-bioavailable Cd(II) (67.23 % of BC500, 59.17 % of Aged-500), and thus showed most promising for Cd(II) immobilization. This study has important practical significance for the long-term application of biochar in real environment.

Programmed pH-responsive core-shell nanoparticles for precisely targeted therapy of ulcerative colitis.

pH-Responsive nanotherapeutics were recently developed for the treatment of ulcerative colitis (UC). However, they target the entire colon rather than the UC site, which leads to insufficient accumulation in inflamed colon lesions and causes side effects. Core-shell nanoparticles exhibit unique advantages in improving the precision of targeted delivery. In this study, Eudragit® EPO and L100, two pH-sensitive materials, were coated on nano-sized curcumin to fabricate core-shell nanoparticles. The developed CNs@EPO@L100 exhibited programmed pH-responsive drug release behavior, improved in vitro anti-inflammatory ability, and enhanced accumulation at the site of inflammation in the colon. Furthermore, after oral administration, CNs@EPO@L100 significantly ameliorated the inflammatory symptoms in mice. Taken together, this study provides insights into programmed release through the rational application of pH-sensitive materials and offers strategies for a precisely targeted therapy of UC using core-shell nanoparticles.

Decoupling of N and P aggravated upward along food chains in an urban river ecosystem.

Anthropogenic input of nutrient has profoundly influenced water quality and aquatic organisms, however, large and unbalanced nitrogen (N) and phosphorus (P) inputs (decoupling) can lead to a range of ecological health problems such as eutrophication. Whether and how the decoupling varies along the aquatic food chain remains poorly addressed. Here we chose an urban river ecosystem in the cosmopolis region of Beijing, with reclaimed water as the entire replenishment water source over 20 years, to demonstrate the decoupling pattern of N vs P across trophic levels. Results showed that organism C, N and P concentration increased, but N:P ratio decreased upward along the food chains, suggesting that this decoupling of N and P increased as trophic level ascends. Compared with natural freshwater ecosystem, the decoupling of N and P was aggravated in the reclaimed water river. Moreover, the homeostasis of N and P were higher at higher relative to lower trophic levels, and higher in macro-food chain relative to planktonic food chain. This study, for the first time, revealed the increasing decoupling of N vs P upward along the major food chains in an urban aquatic ecosystem, and could improve the understanding of nutrient cycling at the food chain level under human disturbance, and provide useful information for ecological restoration and eutrophication control of urban wetlands replenished with reclaimed water.

U-shaped Association Between Folic Acid Supplementation and the Risk of Gestational Diabetes Mellitus in Chinese Women.

OBJECTIVE: Our aim in this study was to assess the association between folic acid (FA) supplementation before and during pregnancy and risk of gestational diabetes mellitus (GDM) in Chinese women. METHODS: This case-control study was conducted at 2 hospitals in central China. A total of 1,300 pregnant women, including 396 GDM patients and 904 controls, participated in the study. Information on the dose and duration of FA supplementation was collected using a self-report questionnaire at enrolment (24 to 28 weeks of gestation). RESULTS: We observed a U-shaped association between FA supplementation and GDM risk that demonstrated a 228% increased risk of GDM among women who never took FA supplements, a 28% increased risk among women who took supplements containing <400 µg/day FA or took FA supplements for <1 month and a 188% increased risk among women who took supplements containing ≥800 µg/day FA for an adequate duration (>1 month before pregnancy and >3 months during pregnancy) compared with women who took supplements containing 400 to 799 µg/day FA for an adequate duration (all p<0.05). For women who took supplements containing ≥800 µg/day FA for an adequate duration, the association between FA supplementation and GDM risk appeared to be stronger among those women with a prepregnancy body mass index (BMI) of ≥25 kg/m2 than among those with a prepregnancy BMI of <25 kg/m2 (p=0.006 for interaction). CONCLUSIONS: There was a U-shaped association of FA supplementation with GDM risk; that is, FA supplementation both below and above the recommended levels may increase the risk of GDM.