The clinical significance of inflammatory mediators in predicting obesity and progression-free survival in patients with adult-onset Craniopharyngioma.

BACKGROUND: Craniopharyngioma (CP) is a rare malformational tumor characterized by high rates of recurrence and morbid obesity. However, the role of inflammatory mediators in obesity and the prognosis of patients with CP remains unknown. Therefore, the present study aimed to analyze associations of inflammatory mediators with weight-related outcomes and the prognosis of patients with CP. METHODS: A total of 130 consecutive patients with CP were included in this study. The expression levels of seven inflammatory mediators and the plasma leptin concentration were investigated. Clinical parameters, weight changes, new-onset obesity, and progression-free survival (PFS) were recorded. The relationships between inflammatory mediators, clinicopathologic parameters, weight-related outcomes, and PFS were explored. RESULTS: Compared with those in normal pituitary tissue, the expressions of inflammatory mediators in tumor tissue were higher. Higher expression levels of CXCL1 and CXCL8 were identified as independent risk factors for significant weight gain, and CXCL1 and TNF were identified as independent risk factors for new-onset postoperative obesity. Poor PFS was associated with higher expression levels of CXCL1, CXCL8, IL1A, IL6, and TNF. CONCLUSION: The present study revealed that inflammatory mediators are associated with morbid obesity in patients with CP. Inflammatory mediators may be the critical bridge between elevated leptin and weight-related outcomes. Additionally, PFS was associated with the expression of inflammatory mediators. Further research is needed to elucidate the underlying mechanisms of inflammatory mediators and their potential as targets for novel therapies for CP.

Gut microbiota composition and metabolic characteristics in patients with Craniopharyngioma.

BACKGROUND: Emerging evidence suggests that the gut microbiota is associated with various intracranial neoplastic diseases. It has been observed that alterations in the gut microbiota are present in gliomas, meningiomas, and pituitary neuroendocrine tumors (Pit-NETs). However, the correlation between gut microbiota and craniopharyngioma (CP), a rare embryonic malformation tumor in the sellar region, has not been previously mentioned. Consequently, this study aimed to investigate the gut microbiota composition and metabolic patterns in CP patients, with the goal of identifying potential therapeutic approaches. METHODS: We enrolled 15 medication-free and non-operated patients with CP and 15 healthy controls (HCs), conducting sequential metagenomic and metabolomic analyses on fecal samples to investigate changes in the gut microbiota of CP patients. RESULTS: The composition of gut microbiota in patients with CP compared to HCs show significant discrepancies at both the genus and species levels. The CP group exhibits greater species diversity. And the metabolic patterns between the two groups vary markedly. CONCLUSIONS: The gut microbiota composition and metabolic patterns in patients with CP differ significantly from the healthy population, presenting potential new therapeutic opportunities.

A Sequencing-Based Phylogenetic Analysis of Various Strains of Watermelon Silver Mottle Virus in Northern China and Their One-Step Detection Using Reverse Transcription Loop-Mediated Isothermal Amplification.

Watermelon silver mottle virus (WSMoV), a potentially invasive virus, is known to reduce the yield and degrade the quality of infected crops in Cucurbitaceae and Solanaceae families, resulting in significant economic losses in limited areas of several Asian countries. WSMoV, previously detected on various crops in southern China, has now become more prevalent on watermelon and sweet pepper in the northern cities of China for the first time. A sequencing-based phylogenetic analysis has confirmed that the viral strains infecting cucumber, watermelon, and sweet pepper plants in Shandong Province are most closely related to those isolated from Guangdong, Guangxi, and Taiwan, suggesting a farther and continuous spread of WSMoV throughout China. To develop a fast, accurate, and practical protocol for WSMoV detection, we designed a set of primers from the conserved sequence of the WSMoV nucleocapsid protein (N) gene for a one-step assay based on reverse transcription loop-mediated isothermal amplification (RT-LAMP). The RT-LAMP assay was performed successfully for 50 min at 61°C and exhibited a highly specific result without cross-reactions with other similar viruses and a sensitivity that is 100-fold higher than that of the traditional RT-PCR. The confirmation of 26 WSMoV suspect samples collected from various regions in Shandong through the RT-LAMP testing has demonstrated that the assay is suitable and practical for detection of WSMoV in both laboratory and field settings.

Effects of Univariate Stiffness and Degradation of DNA Hydrogels on the Transcriptomics of Neural Progenitor Cells.

Mechanical interactions between cells and extracellular matrix (ECM) are critical for stem cell fate decision. Synthetic models of ECM, such as hydrogels, can be used to precisely manipulate the mechanical properties of the cell niche and investigate how mechanical signals regulate the cell behavior. However, it has long been a great challenge to tune solely the ECM-mimic hydrogels' mechanical signals since altering the mechanical properties of most materials is usually accompanied by chemical and topological changes. Here, we employ DNA and its enantiomers to prepare a series of hydrogels with univariate stiffness regulation, which enables a precise interpretation of the fate decision of neural progenitor cells (NPCs) in a three-dimensional environment. Using single-cell RNA sequencing techniques, Monocle pseudotime trajectory and CellphoneDB analysis, we demonstrate that the stiffness of the hydrogel alone does not influence the differentiation of NPCs, but the degradation of the hydrogel that enhances cell-cell interactions is possibly the main reason. We also find that ECM remodeling facilitates cells to sense mechanical stimuli.

[Evidence mapping of clinical research on traditional Chinese medicine in treatment of diabetic foot].

The present study comprehensively summarized the clinical randomized controlled trials(RCTs) and systematic reviews/Meta-analyses of traditional Chinese medicine(TCM) in the treatment of diabetic foot by evidence mapping and clarified the distribution of evidence in this field.CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Web of Science were searched for clinical RCTs and systematic reviews on TCM in the treatment of diabetic foot published in the past ten years.The evidence was analyzed and displayed in the form of text combined with figures and tables.AMSTAR was used for the quality evaluation of systematic reviews.A total of 1 037 clinical RCTs and 20 systematic reviews/Meta-analyses were included.The overall publishing trend was stable, and the scale of RCTs was small.TCM interventions for diabetic foot mainly included external application and foot bath.Much attention was paid to the outcome indicators including total effective rate, ankle brachial index(ABI), and TCM syndromes, while less attention to neuropathy scores, emotional psychology, and long-term prognosis.The overall quality of systematic reviews was low, and the majority of studies indicated that TCM had potential efficacy in treating diabetic foot, and there was still a lack of clear clinical evidence of efficacy.TCM has both advantages and problems in the treatment of diabetic foot.At present, there is still a lack of high-quality research, suggesting that more large-sample, multi-center RCTs should be launched in the future, and the quality of related systematic reviews/Meta-analyses should be improved to fully explore and give full play to the advantages of TCM in the treatment of diabetic foot, and promote the development of the clinical and evidence-based medicine of TCM in the treatment of diabetic foot.

Suprasellar arachnoid cysts: systematic analysis of 247 cases with long-term follow-up.

At present, limited data exists to discuss the characteristics of suprasellar arachnoid cysts (SACs). The aim of this study is to elucidate the relationship between characteristics of cysts and outcomes, quantitatively analyze improvement in hydrocephalus, and evaluate the risk factors for the prognosis of SACs treated by endoscope. From June 2002 to 2017 December, 247 cases of SACs treated by endoscope in Beijing Tiantan Hospital were included in this study. The severity of hydrocephalus was evaluated by Evans' index (EI). The results showed that the slit-valve and the transparent/thin membrane were noted in 86.2% and 76.5% of overall patients, respectively, and the distribution differences among age-groups were statistically significant (p < 0.01). After a mean follow-up duration of 73.1 months, 18 patients underwent a reoperation. Ventriculocystostomy (VC) (hazard ratio (HR), 3.37; 95% confidence interval (CI), 1.2-9.47; p = 0.024) and history of treatment (HR, 3.98; 95% CI, 1.31-12.31; p = 0.015) were adverse factors for reoperation rate. MRI at 1-year follow-up revealed mean decreases of 78.4% and 9.13% in cyst size and EI. No paraventricular edema was an adverse factor associated with the improvement in hydrocephalus (HR, 11.22; 95% CI, 5.43-23.18; p < 0.01). These results indicated that ventriculocystocisternostomy (VCC) and no history of treatment is favorable factors for prognosis of SACs treated by endoscope. If feasible, VCC is the optimal choice for SACs. Slit-valve phenomenon and transparent/thin membrane are correlated with age but did not influence the outcomes of endoscopic fenestration. The mechanism for the expansion of cysts may be different between child and adult patients. Paraventricular edema is a favorable factor for the improvement in hydrocephalus after endoscopic surgery.

Suprasellar arachnoid cysts in adults: clinical presentations, radiological features, and treatment outcomes.

A tendency for suprasellar arachnoid cysts (SACs) to occur in young children is known. Data of adult SACs were rare in previous reports. The aim of this study is to discuss their clinical presentations, radiological features, and treatment outcomes based on 23 adult patients who underwent endoscopic fenestration in our hospital between January 2003 and December 2018. Preoperative cyst volume ranged from 12.3 to 72.5 cm3 (mean 39.8 ± 19.8). Endocrine disorders occurred in 7 (30.4%) patients. Hydrocephalus was observed in 20 patients. In the patients with hydrocephalus, the mean preoperative Evans' index (EI) (%) and frontooccipital horn ratio (FOHR) (%) were 44.8 (ranged 32.2-63.4) and 49.6 (ranged 36.7-59.8), respectively. A bivariate correlation showed significant positive association between preoperative cyst volume and preoperative EI or FOHR (Pearson correlation, r = 0.607, p = 0.005; r = 0.583, p = 0.007). The slit-valve phenomenon was observed in 13 (56.5%) patients. Pale/tenacious cyst walls were observed in 12 (52.2%) patients. Postoperatively, all patients achieved the improvement in clinical symptoms and a decrease in cyst size. The mean decreases in cyst volume, EI, and FOHR were 64.7%, 7.89%, and 5.8%, respectively. A bivariate correlation indicated the irrelevance between the postoperative cyst volume and postoperative EI or FOHR (Pearson correlation: r = 0.37, p = 0.11; r = 0.43, p = 0.054). These results reveal that there are a few differences in several aspects between adult patients and child patients. The severity of hydrocephalus is correlated with cyst size in adult patients. Additionally, the excellent outcomes in adult SACs can be obtained by endoscopic fenestration.

Investigating Permeation Behavior of Flufenamic Acid Cocrystals Using a Dissolution and Permeation System.

The dissolution and permeation of the cocrystals, flufenamic acid-nicotinamide (FFA-NIC) and flufenamic acid-theophylline (FFA-TP), have been investigated in the presence of two polymers, polyvinylpyrrolidone (PVP) and copolymer of vinylpyrrolidone/vinyl acetate (PVP-VA), using a dissolution/permeation (D/P) system. It showed that the types and concentrations of the polymers and their interactions with the coformers had significant effects on the dissolution and permeation of the FFA cocrystals. The role of PVP as a stabilizing agent was not altered in spite of its interaction with the coformer of NIC or TP, which was supported by the proportional flux rate of FFA to the dissolution performance parameter (DPP). With an appropriate PVP concentration, the maximal flux rate of FFA could be obtained for a given FFA cocrystal. The situation was complicated in the presence of PVP-VA. The role of PVP-VA could change because of its association with the coformers, i.e., from a stabilizing agent to a solubilization agent. In addition, PVP-VA reduced the flux rate of FFA, in contrast to its DPP for FFA cocrystals. Finally, 1H NMR provided evidence regarding the molecular interactions between FFA, coformers, and polymers at the atomic level and gave insight into the mechanism underlying the supersaturated solution and subsequent permeation behavior of the cocrystals.

Facile preparation of a nano-imprinted polymer on magnetite nanoparticles for the rapid separation of lead ions from aqueous solution.

A novel nanostructured magnetic ion-imprinted polymer (IIP) was synthesized for the selective adsorption of Pb(ii) from aqueous solution. The IIP was prepared on functional Fe3O4@SiO2 core/shell nanoparticles as a support. Monomer units in the polymer featured the typical bidentate ligand itaconic acid. We used ethylene glycol dimethacrylate and 2,2-azoisobisbutyronitrile as a cross-linker and an initiator, respectively. Monomers with different acid-base properties and different proportions of cross-linker were investigated to obtain high-performance adsorbents. Our results showed that the IIP prepared from itaconic acid had a high adsorption capacity owing to the strong binding between the monomer and Pb(ii) template ion. The IIPs were characterized using Fourier transform infrared spectroscopy, Brunauer-Emmett-Teller surface area analysis, thermogravimetric analysis, and transmission electron microscopy. We confirmed the formation of a nano-imprinted shell layer on the surface of Fe3O4@SiO2. The adsorption rate was fast, conforming to a pseudo-second-order kinetic and Langmuir adsorption model; the adsorption mechanism was deemed to be chemisorption as a single molecular layer. The maximum adsorption capacity of the IIP (51.2 mg g-1) was approximately three times as large as that of the non-imprinted polymer (17.9 mg g-1). The selectivity factors for Pb(ii) in mixed solutions of Pb(ii)/Co(ii), Pb(ii)/Cu(ii), and Pb(ii)/Zn(ii) were 45.6, 6.45, and 8.3, respectively. Pb-IIP exhibited a high selectivity towards Pb(ii), which enabled the enrichment of Pb(ii) in aqueous solution.

Insight into Flufenamic Acid Cocrystal Dissolution in the Presence of a Polymer in Solution: from Single Crystal to Powder Dissolution.

Effects of three polymers, polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), and copolymer of vinylpyrrolidone/vinyl acetate (PVP-VA), on the dissolution behavior of the cocrystals of flufenamic acid with theophylline (FFA-TP CO) and nicotinamide (FFA-NIC CO) were investigated at multiple length scales. At the molecular level, the interactions of crystal surfaces with a polymer were analyzed by observing etching pattern changes using atomic force microscopy. At the macroscopic scale, dissolution rates of particular faces of a single crystal were determined by measurement of the physical retreat velocities of the faces using optical light microscopy. In the bulk experiments, the FFA concentration in a dissolution medium in the absence or presence of a polymer was measured under both sink and nonsink conditions. It has been found that the dissolution mechanisms of FFA-TP CO are controlled by the defect sites of the crystal surface and by precipitation of the parent drug FFA as individual crystals in the bulk fluid. In contrast, the dissolution mechanisms of FFA-NIC CO are controlled by surface layer removal and by a surface precipitation mechanism, where the parent drug FFA precipitates directly onto the surface of the dissolving cocrystals. Through controlling the dissolution environment by predissolving a polymer, PVP or PVP-VA, which can interact with the crystal surface to alter its dissolution properties, improved solubility, and dissolution rates of FFA-TP CO and FFA-NIC CO have been demonstrated.

[Concerns about neonates discharged against medical advice from the neonatal intensive care unit].

Discharge against medical advice (DAMA) conflicts with the purpose of disease treatment in children. Some research has shown that there are high proportions of extremely preterm infants and infants with asphyxia or congenital malformation in neonates with DAMA. This suggests that the sustainable development of neonatology needs cooperation and co-development with obstetrics, neonatal surgery, and radiology to reduce the rate of DAMA. With reference to the current status of research in both China and other countries, this article reviews the causes for DAMA and the strategies for reducing the rate of DAMA, in order to provide a theoretical basis for effectively reducing the rate of DAMA from the neonatal intensive care unit, improving treatment outcomes of the neonates, and increasing hospitals' comprehensive benefits.

High-Performance Sulfurized Polyacrylonitrile Cathode by Using MXene as a Conductive and Catalytic Binder for Room-Temperature Na/S Batteries.

Sulfurized polyacrylonitrile (PAN@S) is a promising cathode material for room-temperature Na/S batteries but suffers from low conductivity and insufficient electrochemical activity, resulting in unsatisfactory actual capacity and rate performance. Herein, Ti3C2Tx MXene nanosheets are used as a conductive and catalytic binder to establish the PAN@S electrode, wherein MXene constructs a highly conductive framework for fast charge transport and provides high catalytic effect to improve the active material utilization and accelerate the redox kinetics significantly. Therefore, the PAN@S electrode bonded by MXene shows an electronic conductivity of 5.05 S cm-1, 4 orders of magnitude higher than the conventional electrodes bonded by the insulative polymer binders, and much decreased activation energy barrier and resistance. Consequently, the PAN@S electrode displays superior performance in terms of high capacity (697.3 mAh g-1 at 200 mA g-1), unparalleled rate capability (189.0 mAh g-1 at 20 A g-1), and excellent high-rate cycling performance (a capacity decay rate of ∼0.04% per cycle during 1000 cycles at 5 A g-1). This work provides a high-performance electrode for room-temperature Na/S batteries and shows the promising potential of conductive and catalytic MXene binders in boosting the performance of active materials.

Risk factors for cerebrospinal fluid leak after extended endoscopic endonasal surgery for adult patients with craniopharyngiomas: a multivariate analysis of 364 cases.

OBJECTIVE: Over the last decade, the extended endoscopic endonasal approach (EEEA) has evolved as a credible surgical alternative for removing craniopharyngiomas. However, postoperative cerebrospinal fluid (CSF) leak remains one of the most pressing concerns. Craniopharyngiomas often invade the third ventricle, resulting in a higher rate of third ventricle opening after surgery and potentially increasing the risk of postoperative CSF leak. Identifying the risk factors associated with CSF leak after EEEA for craniopharyngiomas may have more clinical value. Nevertheless, there is a lack of systematic studies on the topic. Previous studies yielded inconsistent results, probably due to heterogeneous pathologies or small sample sizes. Hence, the authors present the largest known single-institution case series of the use of purely EEEA for craniopharyngiomas to systematically study the risk factors for postoperative CSF leak. METHODS: The authors retrospectively reviewed 364 cases of adult patients with craniopharyngiomas who were treated at their institution from January 2019 to August 2022, and they analyzed the risk factors for postoperative CSF leak. RESULTS: The overall rate of postoperative CSF leak was 4.7%. In the univariate analysis, larger dural defect size (OR 8.293, 95% CI 3.711-18.534, p < 0.001) and lower preoperative serum albumin level (OR 0.812, 95% CI 0.710-0.928, p = 0.002) were associated with higher rates of postoperative CSF leak. Predominantly cystic tumors (OR 0.325, 95% CI 0.122-0.869, p = 0.025) were linked to decreased risk of postoperative CSF leak. However, postoperative lumbar drainage (OR 2.587, 95% CI 0.580-11.537, p = 0.213) and third ventricle opening (OR 1.718, 95% CI 0.548-5.384, p = 0.353) were not related to postoperative CSF leak. In the multivariate analysis, larger dural defect size (OR 8.545, 95% CI 3.684-19.821, p < 0.001) and lower preoperative serum albumin level (OR 0.787, 95% CI 0.673-0.919, p = 0.002) were identified as independent risk factors for postoperative CSF leak. CONCLUSIONS: The authors' repair technique yielded a reliable reconstructive outcome for high-flow CSF leak in EEEA for craniopharyngioma. Lower preoperative serum albumin level and larger dural defect size were identified as independent risk factors for postoperative CSF leak, potentially providing new insights into minimizing the risk of postoperative CSF leak. Third ventricle opening was not associated with postoperative CSF leak. Lumbar drainage may not be necessary for high-flow intraoperative leak, but this finding may require validation with a prospective randomized controlled trial in the future.

Ultralong Stability of Ti3 C2 Tx -MXene Dispersion Through Synergistic Regulation of Storage Environment and Defect Capping with Tris-HCl Buffering.

Aqueous MXene dispersion suffers from a bottleneck issue of oxidation, leading to its gradual deterioration and ultimately compromised physicochemical characteristics. Herein, Tris-HCl buffer is employed to stabilize the diluted Ti3 C2 Tx -MXene dispersion (0.05 mg mL-1 ) through the synergy of its potent pH-regulation capability and capping effect toward oxidation-susceptible defects/edges. Tris-HCl functionalized Ti3 C2 Tx maintained its original morphology, structure, and favorable dispersity even after 150 days of aging under naturally aerated conditions. The pH-regulation nature of Tris-HCl is elucidated through solution monitoring of Ti3 C2 Tx dispersion, while the adsorption of Tris-HCl onto defects/edges is revealed by spectral analysis and multi-scale simulations. Tris-HCl at the neutral pH can bind to the negatively charged basal plane of Ti3 C2 Tx via + HTris moiety, while the other moiety (Tris) interacts with the exposed edge-based Ti atoms and/or intrinsic defects, forming a Ti─N bond that prevents MXene from attack by H2 O and O2 . Besides, Tris-HCl stabilized Ti3 C2 Tx exhibited nearly identical capacitive characteristics to its freshly-etched counterpart, indicating the minimal impact of Tris-HCl on electrochemical performance of Ti3 C2 Tx during long-term storage. This study provides practical guidance for stabilizing MXene in their native aqueous dispersion without compromising the inherent properties.

Adult craniopharyngioma concomitant with unruptured intracranial aneurysms: incidence, risk factors, and treatment strategies.

OBJECTIVE: Concomitant unruptured intracranial aneurysms (UIAs) in patients with craniopharyngioma (CP) pose a challenge for surgical management. This study presents the largest known single-institution case series to investigate the incidence of UIA in CP patients, with the aim of exploring the potential risk factors for the occurrence of UIA in CP patients and proposing treatment strategies. METHODS: The authors retrospectively reviewed the records of 289 adult CP patients treated in their department between January 2020 and August 2022. Routine CT angiography (CTA) was performed preoperatively in all cases. Logistic regression analysis was used to identify the risk factors for the occurrence of aneurysms. Aneurysms with the following characteristics were considered to have a high risk of intraoperative rupture and required treatment before tumor resection: 1) preliminary assessment of a high inherent risk of rupture (risk of rupture in their natural progression); and 2) location close to the tumor, irregular shape, and/or growth toward the tumor, even if the preliminary assessment indicated a low inherent risk of rupture. RESULTS: Twenty-three of 289 CP patients (7.96%, 95% CI 5.36-11.6) were diagnosed with both CP and UIA (CP-UIA). Hypertension (OR 4.148, 95% CI 1.654-10.398; p = 0.002), estrogen deficiency (OR 3.097, 95% CI 1.241-7.731; p = 0.015), and suprasellar tumor (OR 4.316, 95% CI 1.596-11.67; p = 0.004) were independent risk factors for intracranial aneurysms (IAs) in CP patients. Among the 23 CP-UIA patients, 6 (26.1%) with a high risk of aneurysm rupture underwent endovascular treatment (EVT) before tumor resection. Seventeen (73.9%) patients with a low risk of rupture underwent tumor resection only. CONCLUSIONS: The incidence rate of IA in patients with CP was higher than that in the general population. Routine preoperative CTA is advised for adult CP patients. Patients with papillary CP exhibited a higher proportion of CP-UIAs. Older age, hypertension, estrogen deficiency, and suprasellar tumor were independent risk factors for the occurrence of IAs in CP patients. IAs in CP patients are predominantly located in the C6 and C7 segments of the internal carotid artery and are often suitable for EVT. When treating CP-UIAs, tumor-related symptoms, risk of aneurysm rupture, the spatial relationship between the tumor and IA, and the approach for tumor resection should be considered.

Spike-based dynamic computing with asynchronous sensing-computing neuromorphic chip.

By mimicking the neurons and synapses of the human brain and employing spiking neural networks on neuromorphic chips, neuromorphic computing offers a promising energy-efficient machine intelligence. How to borrow high-level brain dynamic mechanisms to help neuromorphic computing achieve energy advantages is a fundamental issue. This work presents an application-oriented algorithm-software-hardware co-designed neuromorphic system for this issue. First, we design and fabricate an asynchronous chip called "Speck", a sensing-computing neuromorphic system on chip. With the low processor resting power of 0.42mW, Speck can satisfy the hardware requirements of dynamic computing: no-input consumes no energy. Second, we uncover the "dynamic imbalance" in spiking neural networks and develop an attention-based framework for achieving the algorithmic requirements of dynamic computing: varied inputs consume energy with large variance. Together, we demonstrate a neuromorphic system with real-time power as low as 0.70mW. This work exhibits the promising potentials of neuromorphic computing with its asynchronous event-driven, sparse, and dynamic nature.

Pharmacokinetics, safety, and efficacy of Fuqi Guben Gao in the treatment of kidney-yang deficiency syndrome: a randomized, double-blind phase I trial.

Introduction: Fuqi Guben Gao (FQGBG) is a botanical drug formulation composed of FuZi (FZ; Aconitum carmichaelii Debeaux [Ranunculaceae; Aconiti radix cocta]), Wolfberry (Lycium barbarum L. [Solanaceae; Lycii fructus]), and Cinnamon (Neolitsea cassia (L.) Kosterm. [Lauraceae; Cinnamomi cortex]). It has been used to clinically treat nocturia caused by kidney-yang deficiency syndrome (KYDS) for over 30 years and warms kidney yang. However, the pharmacological mechanism and the safety of FQGBG in humans require further exploration and evaluation. Methods: We investigated the efficacy of FQGBG in reducing urination and improving immune organ damage in two kinds of KYDS model rats (hydrocortisone-induced model and natural aging model), and evaluated the safety of different oral FQGBG doses through pharmacokinetic (PK) parameters, metabonomics, and occurrence of adverse reactions in healthy Chinese participants in a randomized, double-blind, placebo-controlled, single ascending dose clinical trial. Forty-two participants were allocated to six cohorts with FQGBG doses of 12.5, 25, 50, 75, 100, and 125 g. The PKs of FQGBG in plasma were determined using a fully validated LC-MS/MS method. Results: FQGBG significantly and rapidly improved the symptoms of increased urination in both two KYDS model rats and significantly resisted the adrenal atrophy in hydrocortisone-induced KYDS model rats. No apparent increase in adverse events was observed with dose escalation. Major adverse drug reactions included toothache, thirst, heat sensation, gum pain, diarrhea, abdominal distension, T-wave changes, and elevated creatinine levels. The PK results showed a higher exposure level of benzoylhypaconine (BHA) than benzoylmesaconine (BMA) and a shorter half-life of BMA than BHA. Toxic diester alkaloids, aconitine, mesaconitine, and hypaconitine were below the lower quantitative limit. Drug-induced metabolite markers primarily included lysophosphatidylcholines, fatty acids, phenylalanine, and arginine metabolites; no safety-related metabolite changes were observed. Conclusion: Under the investigated dosing regimen, FQGBG was safe. The efficacy mechanism of FQGBG in treating nocturia caused by KYDS may be related to the improvement of the hypothalamus-pituitary-adrenal axis function and increased energy metabolism. Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=26934, identifier ChiCTR1800015840.

Effectiveness and Safety of Qishen Yiqi Dripping Pill in Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention: 3-Year Results from a Multicentre Cohort Study.

OBJECTIVES: To evaluate the effectiveness and safety of Qishen Yiqi Dripping Pill (QSYQ) in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). METHODS: This multicentre prospective cohort study was conducted at 40 centers in China. Patients with ACS after PCI entered either the QSYQ or Western medicine (WM) groups naturally based on whether they had received QSYQ before enrollment. QSYQ group received QSYQ (0.52 g, 3 times a day for 12 months) in addition to WM. The primary endpoint included cardiac death, non-fatal myocardial infarction, and urgent revascularization. The secondary endpoint included rehospitalization due to ACS, heart failure, stroke, and other thrombotic events. Quality of life was assessed by the Seattle Angina Questionnaire (SAQ). RESULTS: A total of 936 patients completed follow-up of the primary endpoint from February 2012 to December 2018. Overall, 487 patients received QSYQ and WM. During a median follow-up of 566 days (inter quartile range, IQR, 517-602), the primary endpoint occurred in 46 (9.45%) and 65 (14.48%) patients in QSYQ and WM groups respectively [adjusted hazard ratio (HR) 0.60, 95% confidence interval (CI) 0.41-0.90; P=0.013]. The secondary endpoint occurred in 61 (12.53%) and 74 (16.48%) patients in QSYQ and WM groups, respectively (adjusted HR 0.76, 95% CI 0.53-1.09; P=0.136). In sensitivity analysis, the results still demonstrated that WM combined with QSYQ reduced the risk of the primary endpoint (HR 0.67, 95% CI 0.46-0.98; P=0.039). Moreover, QSYQ improved the disease perception domain of the SAQ (P<0.05). CONCLUSION: In patients with ACS after PCI, QSYQ combined with WM reduced the incidence of the primary endpoint. These findings provide a promising option for managing ACS after PCI and suggest the potential treatment for reducing the risk of primary endpoint included cardiac death, non-fatal myocardial infarction, and urgent revascularization through intermittent administration of QSYQ (Registration No. ChiCTR-OOC-14005552).

Research Progress of Plant Active Ingredients in Pharmaceutical Cocrystal.

The disadvantages of active ingredients extracted from medicinal plants due to poor solubility in the body and low bioavailability limit their clinical application. Pharmaceutical cocrystal as a new type of drug in solid form has attracted the attention of researchers. This article reviews the effects of cocrystal in various poorly soluble herbal active ingredients of medicinal plants on their physicochemical properties and biological properties and provides references for the application of pharmaceutical cocrystal in poorly soluble active compounds of medicinal plants.

Identification and characterization of plant-derived biomarkers and physicochemical variations in the maturation process of Triadica cochinchinensis honey based on UPLC-QTOF-MS metabolomics analysis.

The maturation patterns of nectar into honey are not well understood. The current work selected Triadica cochinchinensis honey (TCH) at three maturity stages to systematically investigate the variation patterns in physicochemical parameters and metabolites. Based on both targeted and untargeted metabolomics analyses, the N1, N5, N10-(E)-tricoumaryl spermidine was identified as the plant-derived characteristic compound in TCH. A total of 26 compounds were quantified by UPLC-QTOF-MS using an external standard calibration method. Two patterns of the honey maturation process were identified based on the 723 metabolite signature transformations. The first was that the levels of plant-derived compounds with strong reducing activity were reduced, such as spermidine, flavonoids, and their derivatives. In contrast, the second pattern was that the maturation process of honey was accompanied by the formation of lactone glycoside analogs and organic acids, which may be facilitated by the enzymatic transformation of enzymes secreted by the bees.