Advances in Flavonoid Research: Sources, Biological Activities, and Developmental Prospectives.

At present, the occurrence of a large number of infectious and non-communicable diseases poses a serious threat to human health as well as to drug development for the treatment of these diseases. One of the most significant challenges is finding new drug candidates that are therapeutically effective and have few or no side effects. In this respect, the active compounds in medicinal plants, especially flavonoids, are potentially useful compounds with a wide range of pharmacological activities. They are naturally present in nature and valuable in the treatment of many infectious and non-communicable diseases. Flavonoids are divided into fourteen categories and are mainly derived from plant extraction, chemical synthesis and structural modification, and biosynthesis. The structural modification of flavonoids is an important way to discover new drugs, but biosynthesis is currently considered the most promising research direction with the potential to revolutionize the new production pipeline in the synthesis of flavonoids. However, relevant problems such as metabolic pathway analyses and cell synthesis protocols for flavonoids need to be addressed on an urgent basis. In the present review, new research techniques for assessing the biological activities of flavonoids and the mechanisms of their biological activities are elucidated and their modes of interaction with other drugs are described. Moreover, novel drug delivery systems, such as nanoparticles, bioparticles, colloidals, etc., are gradually becoming new means of addressing the issues of poor hydrophilicity, lipophilicity, poor chemical stability, and low bioavailability of flavonoids. The present review summarizes the latest research progress on flavonoids, existing problems with their therapeutic efficacy, and how these issues can be solved with the research on flavonoids.

Knowledge structure and future research trends of body-mind exercise for mild cognitive impairment: a bibliometric analysis.

Background: Mild cognitive impairment (MCI) is a common neurodegenerative disorder that poses a risk of progression to dementia. There is growing research interest in body-mind exercise (BME) for patients with MCI. While we have observed a rapid growth in interest in BME for MCI over the past 10 years, no bibliometric analysis has investigated the knowledge structure and research trends in this field. Consequently, the objective of this research is to conduct a bibliometric analysis of global publications of BME for MCI from 2013 to 2022. Methods: A total of 242 publications in the field of BME for MCI were retrieved from the Web of Science Core Collection. Bibliometric analysis, including performance analysis, science mapping, and visualization, was performed using CiteSpace, VOSviewer, and Microsoft Excel. Results: Publications and citations in the field of BME for MCI have shown a rapidly increasing trend over the last decade. Geriatrics & Gerontology, and Neurosciences were the most frequently involved research categories. China (78 documents) and the USA (75 documents) contributed to the largest number of publications and had the strongest international collaborative networks. Fujian University of Traditional Chinese Medicine contributed to the largest number of publications (12 documents), and Chen, L of this institution was the most prolific author (12 documents). Frontiers in Aging Neuroscience (16 documents), and JOURNAL OF ALZHEIMER'S DISEASE (12 documents) were the most prolific journals. Tai Chi and Baduanjin, as specific types of BME, were the hotspots of research in this field, while evidence synthesis and guidelines might be future research trends. Conclusion: In the last decade, there has been a rapid growth in scientific activities in the field of BME for MCI. The results of this study provide researchers and other stakeholders with knowledge structure, hotspots, and future research trends in this field.

[Role of macrophage polarization in hypertension and traditional Chinese medicine intervention: a review].

Hypertension is known to be a chronic inflammatory state and a key risk factor for heart failure, coronary heart disease, and atherosclerosis. Macrophages in the circulatory system are the main cell group that constitutes the immune system and participates in the inflammatory response. Depending on the local microenvironment, macrophages can be polarized into pro-inflammatory(M1) and anti-inflammatory(M2) phenotypes. When blood pressure is elevated, M1 macrophages can release pro-inflammatory cytokines and chemokines to generate an immune response. However, an excessive immune response can lead to tissue damage, and M2 macrophages release anti-inflammatory cytokines to promote the repair of wounds and tissue damage. It is clear that the dynamic balance between M1 and M2 macrophages resembles the traditional Chinese medicine(TCM) theory of Yin and Yang. That is, when Yin and Yang are imbalanced, the human body will exhibit pathological states, e.g., altered blood pressure rhythms. Studies have confirmed that TCM can produce positive therapeutic effects on hypertension by regulating macrophage polarization. Therefore, this study reviews the studies about the TCM regulation of macrophage polarization and summarized the mechanisms of TCM intervention in hypertension, with the aim of providing evidence for clinical treatment and ideas for scientific research design.

The material basis of bitter constituents in Carbonized Typhae Pollen, based on the integration strategy of constituent analysis, taste sensing system and molecular docking.

The discovery of bitter constituents is of great significance to the exploration of medicinal substances for they have potential physiological effects. Carbonized Typhae Pollen (CTP), which is a typical example of carbonized Traditional Chinese Medicine (TCM), has a bitter taste and hemostatic effect after carbonized processing. The objective of this study is to elucidate the material basis of bitter constituents in CTP. Firstly, the constituents of CTP extracts with 7 different solvents were characterized by UPLC-Q-TOF-MS. Then, multivariate statistical analysis was used to visualize the CTP extracts from 7 solvents. A total of 37 constituents were tentatively identified and 17 constituents were considered as the key constituents in differentiating 7 different solvent extracts. Subsequently, the bitter evaluation of extracts from different polar parts was investigated by using an electronic tongue. As a result, the order of bitterness of the extracts was as follows: ethanol > methanol > water > n-butyl alcohol > petroleum ether > butyl acetate > isopropanol. There were statistically significant differences in the bitter degree of extracts. By correlation analysis of bitter information and chemical constituents with partial least squares regression (PLSR), 8 potential bitterness constituents were discovered, including phenylalanine, valine, chlorogenic acid, isoquercitrin, palmitic acid, citric acid, quercetin-3-O-(2-α-L-rhamnosyl)-rutinoside, and typhaneoside. Additionally, molecular docking analysis was conducted to reveal the interaction of these constituents with the bitter taste receptor. The docking result showed that these constituents could be embedded well into the active pocket of T2R46 and had significant affinity interactions with critical amino acid residues by forming hydrogen bonds. This study provided a reliable theoretical basis for future research on biological activity of bitterness substances.

Ethanol extract of Evodia lepta Merr. ameliorates cognitive impairment through inhibiting NLRP3 inflammasome in scopolamine-treated mice.

Evodia lepta Merr. (Evodia lepta) is a well-known traditional Chinese medicine, which has been widely used in herbal tea. We previously reported that the coumarin compounds from the root of Evodia lepta exhibited neuroprotective effects. However, whether Evodia lepta could inhibit NLRP3 inflammasome in dementia was still unknown. In this study, the components of the Evodia lepta extract were identified by HPLC-Q-TOF HRMS. We employed a scopolamine-treated mouse model. Evodia lepta extract (10 or 20 mg/kg) and donepezil were treated by gavage once a day for 14 consecutive days. Following the behavioral tests, oxidative stress levels were measured. Then, Western blot and immunofluorescence analysis were used to evaluate the expressions of NLRP3 inflammasome. 14 major components of the Evodia lepta extract were identified by HPLC-Q-TOF HRMS. The results of Morris water maze, object recognition task and open field test indicated that Evodia lepta extract could ameliorate cognitive impairment in scopolamine-treated mice. Evodia lepta extract improved cholinergic system. Moreover, Evodia lepta extract improved the expressions of PSD95 and BDNF. Evodia lepta extract suppressed neuronal oxidative stress and apoptosis. In addition, Evodia lepta extract inhibited NLRP3 inflammasome in the hippocampus of scopolamine-treated mice. Evodia lepta extract could protect against cognitive impairment by inhibiting NLRP3 inflammasome in scopolamine-treated mice.

Least Absolute Shrinkage and Selection Operator-Based Prediction of the Binding Constant of p-Sulfonatocalix[6]/[8]arenes with Alkaloids.

p-Sulfonatocalix[n]arenes (SCnA) have demonstrated great potential for drug encapsulation through host-guest complexation to improve solubility, stability, and bioavailability. In this study, the solubilization effect of SCnA (n = 4, 6, 8) on 95 active compounds derived from traditional Chinese medicine (TCM) was investigated. Based on the significant solubilization effect on alkaloids, SC6A/SC8A and 76 alkaloids were selected as the host and guest, respectively, to determine the binding constant by competitive fluorescence titration. LASSO regression was adopted to investigate the mechanism of the complex of SCnA with alkaloids. The binding constant of alkaloids-SC6A and alkaloids-SC8A was related to the alkaloid alkalinity. Also, the electronegativity, polarization, first ionization potential, hydrogen bond potential, the molecular size, and shape of alkaloids are critical properties to determine alkaloids-SC6A binding constant as well as electronegativity, polarization, hydrophobicity, and the molecular size and shape of alkaloids play an important role for the alkaloids-SC8A binding constant.

Advances in the treatment of malignant ascites in China.

PURPOSE: Malignant ascites (MA) often occurs in recurrent abdominal malignant tumors, and the large amount of ascites associated with cancerous peritonitis not only leads to severe abdominal distension and breathing difficulties, but also reduces the patient's quality of life and ability to resist diseases, which usually makes it difficult to carry out anti-cancer treatment. The exploration of MA treatment methods is also a key link in MA treatment. This article is going to review the treatment of MA, to provide details for further research on the treatment of MA, and to provide some guidance for the clinical treatment of MA. METHOD: This review analyzes various expert papers and summarizes them to obtain the paper. RESULT: There are various treatment methods for MA, including systemic therapy and local therapy. Among them, systemic therapy includes diuretic therapy, chemotherapy, immunotherapy, targeted therapy, anti angiogenic therapy, CAR-T, and vaccine. Local therapy includes puncture surgery, peritoneal vein shunt surgery, acellular ascites infusion therapy, radioactive nuclide intraperitoneal injection therapy, tunnel catheter, and intraperitoneal hyperthermia chemotherapy. And traditional Chinese medicine treatment has also played a role in enhancing efficacy and reducing toxicity to a certain extent. CONCLUSION: Although there has been significant progress in the treatment of MA, it is still one of the clinical difficulties. Exploring the combination or method of drugs with the best therapeutic effect and the least adverse reactions to control MA is still an urgent problem to be solved.

Toward Type I/II ROS Generation Photoimmunotherapy by Molecular Engineering of Semiconducting Perylene Diimide.

As prospective phototheranostic agents for cancer imaging and therapy, semiconducting organic molecule-based nanomedicines are developed. However, near-infrared (NIR) emission, and tunable type I (O2 • -) and type II (1O2) photoinduced reactive oxygen species (ROS) generation to boost cancer photoimmunotherapy remains a big challenge. Herein, a series of D-π-A structures, NIR absorbing perylene diimides (PDIs) with heavy atom bromide modification at the bay position of PDIs are prepared for investigating the optimal photoinduced type I/II ROS generation. The heavy atom effect has demonstrated a reduction of molecular ∆EST and promotion of the intersystem crossing processes of PDIs, enhancing the photodynamic therapy (PDT) efficacy. The modification of three bromides and one pyrrolidine at the bay position of PDI (TBDT) has demonstrated the best type I/II PDT performance by batch experiments and theoretical calculations. TBDT based nanoplatforms (TBDT NPs) enable type I/II PDT in the hypoxic tumor microenvironment as a strong immunogenic cell death (ICD) inducer. Moreover, TBDT NPs showing NIR emission allow in vivo bioimaging guided phototherapy of tumor. This work uses novel PDIs with adjustable type I/II ROS production to promote antitumor immune response and accomplish effective tumor eradication, consequently offering molecular guidelines for building high-efficiency ICD inducers.

Mitochondrial ribosomal protein L12 potentiates hepatocellular carcinoma by regulating mitochondrial biogenesis and metabolic reprogramming.

BACKGROUND: Mitochondrial dysfunction and metabolic reprogramming are key features of hepatocellular carcinoma (HCC). Despite its significance, the precise underlying mechanism behind these processes has not been fully elucidated. The latest investigations, along with our previous discoveries, have substantiated the significant role of mitochondrial ribosomal protein L12 (MRPL12), a newly identified gene involved in mitochondrial transcription regulation, in the modulation of mitochondrial metabolism. Nevertheless, the role of MRPL12 in tumorigenesis has yet to be investigated. METHODS: The expression of MRPL12 in HCC was assessed using an online database. Western blot, quantitative real-time polymerase chain reaction (qRT-PCR), and immunohistochemistry (IHC) were employed to determine the expression of MRPL12 in HCC tissues, patient-derived organoid (PDO), and cell lines. The correlation between MRPL12 expression and clinicopathological features, as well as prognosis, was examined using tissue microarray analysis. An in vivo subcutaneous tumor xenograft model, gene knockdown or overexpression assay, chromatin immunoprecipitation (ChIP) assay, Seahorse XF96 assay, and cell function assay were employed to investigate the biological function and potential molecular mechanism of MRPL12 in HCC. RESULTS: A significant upregulation of MRPL12 was observed in HCC cells, PDO and patient tissues, which correlated with advanced tumor stage, higher grade and poor prognosis. MRPL12 overexpression promoted cell proliferation, migration, and invasion in vitro, as well as tumorigenicity in vivo, whereas MRPL12 knockdown showed the opposite effect. MRPL12 knockdown also inhibited the capacity of organoids proliferation capacity. Furthermore, MRPL12 was found to be crucial for maintaining mitochondrial homeostasis. Both gain and loss-of-function experiments targeting MRPL12 in HCC cells altered oxidative phosphorylation (OXPHOS) and mitochondrial DNA content. Notably, suppression of OXPHOS effectively mitigates the tumor-promoting effect attributed to MRPL12 overexpression, implying the involvement of MRPL12 in HCC through the modulation of mitochondrial metabolism. Besides, Yin Yang 1 (YY1) was identified as a transcription factor responsible for regulating MRPL12, while the PI3K/mTOR pathway was found to act as an upstream regulator of YY1. MRPL12 knockdown attenuated the YY1 overexpression or PI3K/mTOR activation-induced malignant phenotype in HCC cells. CONCLUSION: Our findings provide compelling evidence that MRPL12 is implicated in driving the malignant phenotype of HCC via regulating mitochondrial metabolism. Moreover, the aberrant expression of MRPL12 in HCC is mediated by the upstream PI3K/mTOR/YY1 pathway. These results highlight the potential of targeting MRPL12 as a promising therapeutic strategy for the treatment of HCC.

Electroacupuncture with intermittent wave stimulation as rehabilitation approach for chronic Bell's palsy: a randomized controlled trial.

PURPOSE: To evaluate the effectiveness and safety of electroacupuncture (EA) using intermittent wave stimulation in enhancing facial symmetry and nerve function in chronic Bell's palsy patients. METHODS: A 6-week assessor-blinded, randomized trial followed by an 18-week observational period was conducted. Sixty individuals with chronic Bell's palsy, showing no signs of recovery after 12 months, were equally divided to receive either 18 sessions of EA using intermittent wave stimulation or Transcutaneous Electrical Stimulation (TES), administered thrice weekly over 6 weeks. The primary outcome measure was the change in the total facial nerve index (TFNI) score from baseline to Week 6, with secondary outcomes including TFNI scores at Weeks 12 and 24, as well as the change in Sunnybrook Facial Grading System (SFG) score from baseline to Week 6, and SFG scores at Weeks 12 and 24. RESULTS: The EA group showed a significant improvement, with a mean total facial nerve index score increase of 24.35 (4.77) by Week 6 compared with 14.21 (5.12) in the Transcutaneous Electrical Stimulation group (P<.001). This superiority persisted during the 24-week follow-up. While no significant difference was observed in the Sunnybrook Facial Grading System score change from baseline to Week 6, variations were noted at Weeks 12 and 24. No major adverse effects were reported. CONCLUSION: EA with intermittent wave stimulation notably enhanced facial symmetry in chronic Bell's palsy patients over Transcutaneous Electrical Stimulation by Week 6, maintaining this edge throughout the follow-up.

Enhanced Detection Precision of the Taiji Program by Frequency Setting Strategy Based on a Hierarchical Optimization Algorithm.

For space-based gravitational wave detection, a laser interferometric measurement system composed of a three-spacecraft formation offers the most rewarding bandwidth of astrophysical sources. There are no oscillators available that are stable enough so that each spacecraft could use its own reference frequency. The conversion between reference frequencies and their distribution between all spacecrafts for the synchronization of the different metrology systems is the job of the inter-spacecraft frequency setting strategy, which is important for continuously acquiring scientific data and suppressing measurement noise. We propose a hierarchical optimization algorithm to solve the frequency setting strategy. The optimization objectives are minimum total readout displacement noise and maximum beat-note frequency feasible range. Multiple feasible parameter combinations were obtained for the Taiji program. These optimized parameters include lower and upper bounds of the beat note, sampling frequency, pilot tone signal frequency, ultrastable clock frequencies, and modulation depth. Among the 20 Pareto optimal solutions, the minimum total readout displacement noise was 4.12 pm/Hz, and the maximum feasible beat-note frequency range was 23 MHz. By adjusting the upper bound of beat-note frequency and laser power transmitted by the telescope, we explored the effects of these parameters on the minimum total readout displacement noise and optimal local laser power in greater depth. Our results may serve as a reference for the optimal design of laser interferometry system instrument parameters and may ultimately improve the detection performance and continuous detection time of the Taiji program.

[Potential targets for traditional Chinese medicine treatment of chronic inflammation in obesity: macrophage polarization].

Obesity has been identified as a chronic low-grade systemic inflammation and a key risk factor for diseases such as diabetes, hypertension, and malignancies, and has become an urgent global health burden. Adipose tissue macrophages play a significant role in adipose immune homeostasis and inflammatory responses. Under different conditions, they can be polarized into pro-inflammatory M1 phenotype or anti-inflammatory M2 phenotype. In obese individuals, there is abnormal polarization of macrophages in adipose tissue, leading to an imbalance in the M1/M2 phenotype dynamic equilibrium and the development of pathological inflammation. Therefore, restoring the balance of M1/M2 macrophage polarization is an important potential target for the treatment of chronic inflammation in obesity. Studies have shown that traditional Chinese medicine(TCM) can positively modulate macrophage polarization and produce beneficial effects on obesity. Based on existing evidence, this paper systematically reviewed the potential mechanisms of TCM in improving chronic inflammation in obesity from the perspective of macrophage polarization, in order to provide evidence for the clinical diagnosis and treatment of chronic inflammation in obesity with TCM and offer new insights for related research design and the development of new TCM.

Study on the Alleviating Effect and Potential Mechanism of Ethanolic Extract of Limonium aureum (L.) Hill. on Lipopolysaccharide-Induced Inflammatory Responses in Macrophages.

Inflammation is the host response of immune cells during infection and traumatic tissue injury. An uncontrolled inflammatory response leads to inflammatory cascade, which in turn triggers a variety of diseases threatening human and animal health. The use of existing inflammatory therapeutic drugs is constrained by their high cost and susceptibility to systemic side effects, and therefore new therapeutic candidates for inflammatory diseases need to be urgently developed. Natural products are characterized by wide sources and rich pharmacological activities, which are valuable resources for the development of new drugs. This study aimed to uncover the alleviating effect and potential mechanism of natural product Limonium aureum (LAH) on LPS-induced inflammatory responses in macrophages. The experimental results showed that the optimized conditions for LAH ultrasound-assisted extraction via response surface methodology were an ethanol concentration of 72%, a material-to-solvent ratio of 1:37 g/mL, an extraction temperature of 73 °C, and an extraction power of 70 W, and the average extraction rate of LAH total flavonoids was 0.3776%. Then, data of 1666 components in LAH ethanol extracts were obtained through quasi-targeted metabolomics analysis. The ELISA showed that LAH significantly inhibited the production of pro-inflammatory cytokines while promoting the secretion of anti-inflammatory cytokines. Finally, combined with the results of network pharmacology analysis and protein expression validation of hub genes, it was speculated that LAH may alleviate LPS-induced inflammatory responses of macrophages through the AKT1/RELA/PTGS2 signaling pathway and the MAPK3/JUN signaling pathway. This study preliminarily revealed the anti-inflammatory activity of LAH and the molecular mechanism of its anti-inflammatory action, and provided a theoretical basis for the development of LAH as a new natural anti-inflammatory drug.

Autonomous State Estimation and Observability Analysis for the Taiji Formation Using High-Precision Optical Sensors.

In certain observation periods of navigation missions for the Taiji formation, ground observation stations are unable to observe the spacecraft, while the state of the spacecraft can be estimated through the utilization of dynamic equations simulated on prior knowledge. However, this method cannot accurately track the spacecraft. In this paper, we focus on appropriately selecting the available onboard measurement to estimate the state of the spacecraft of the Taiji formation. We design two schemes to explore the performance of the state estimation based on the interspacecraft interferometry measurements and the measurements obtained from the Sun sensor and the radial velocity sensor. The observability of the system is numerically analyzed using the singular value decomposition method. Furthermore, we analyze error covariance propagation using the cubature Kalman filter. The results show that using high-precision interspacecraft angle measurement can improve significantly the observability of the system. The absolute position and velocity of the spacecraft can be estimated respectively with an accuracy of about 3.1 km and 0.14 m/s in the first scheme, where the prior information of the precision of the position and velocity is respectively 100 km and 1 m/s. When the measurement from the radial velocity sensor is used in the second scheme, the estimation accuracy of the velocity can be improved about 18 times better than that in the first scheme.

Advanced inter-spacecraft offset frequency setting strategy for the Taiji program based on a two-stage optimization algorithm.

For space-based gravitational wave (GW) detection, the continuity of detection data acquisition is crucial to the inversion of wave sources and the realization of scientific goals. To control the inter-spacecraft beat-note frequency in an appropriate range for continuous gravitational wave detection and to reduce the upper bound of the beat-note frequency for improving the detection capability, a two-stage optimization algorithm is proposed to solve the offset frequency setting strategy in the Taiji program. The optimization objectives are the maximum offset frequency duration and minimum upper bound of the beat-note frequency. Considering all feasible phase-locked schemes, Doppler frequency shift, and the bandwidth of the phasemeter, a series of offset frequency setting strategies satisfying the conditions was obtained. The solution results show that the upper bound can be reduced to 16 MHz and, in this case, the offset frequency changes nine times with a minimum and maximum offset frequency duration of 90 days and 713 days, respectively. If the Doppler frequency shift is constrained, the minimum upper bound can be reduced to 14 MHz. When the minimum duration is increased, the minimum upper bound is increased. These results show that, by varying the offset frequency a limited number of times, the data continuity requirements of the Taiji program can be satisfied, and the phasemeter development difficulty and detection capability can be balanced, and may provide a reference for the phasemeter design, the setting of phase-locking schemes, and inter-spacecraft offset frequency in the Taiji program.

Jianpi Decoction Combined with Medroxyprogesterone Acetate Alleviates Cancer Cachexia and Prevents Muscle Atrophy by Directly Inhibiting E3 Ubiquitin Ligase.

OBJECTIVE: To provide comprehensive evidence for the anti-cancer cachexia effect of Jianpi Decoction (JP) and to explore its mechanism of anti-cancer cachexia. METHODS: A mouse model of colon cancer (CT26)-induced cancer cachexia (CC) was used to investigate the anti-CC effect of JP combined with medroxyprogesterone acetate (MPA). Thirty-six mice were equally divided into 6 groups: normal control, CC, MPA (100 mg•kg-1•d-1), MPA + low-dose (20 mg•kg-1•d-1) JP (L-JP), MPA + medium-dose (30 mg•kg-1•d-1) JP (M-JP), and MPA + high-dose (40 mg•kg-1•d-1) JP (H-JP) groups. After successful modeling, the mice were administered by gavage for 11 d. The body weight and tumor volume were measured and recorded every 2 d starting on the 8th day after implantation. The liver, heart, spleen, lung, kidney, tumor and gastrocnemius muscle of mice were collected and weighed. The pathological changes of the tumor was observed, and the cross-sectional area of the gastrocnemius muscle was calculated. The protein expressions of STAT3 and E3 ubiquitinase in the gastrocnemius muscle were measured by Western blot. In addition, an in vitro C2C12 myotube formation model was established to investigate the role of JP in hindering dexamethasone-induced muscle atrophy. In vitro experiments were divided into control, model, and JP serum groups. After 2-d administration, microscopic photographs were taken and myotube diameters were calculated. Western blot was performed to measure the protein expressions of STAT3 and E3 ubiquitinase. RESULTS: JP combined with MPA restored tumor-induced weight loss (P<0.05, vs. CC) and muscle fiber size (P<0.01, vs. CC). Mechanistically, JP reduced the expression of atrophy-related proteins MuRF1 and MAFbx in tumor-induced muscle atrophy in vivo (P<0.05, vs. CC). In addition, JP reduced the expression of atrophy-related proteins MuRF1 and MAFbx and p-STAT3 phosphorylation (P<0.05 or P<0.01 vs. model group) in C2C12 myotubes treated with dexamethasone in vitro. CONCLUSIONS: Administration of JP combined with MPA restores tumor-induced cachexia conditions. In addition, the profound effect of JP combined with MPA on tumor-induced cachexia may be due to its inhibition of muscle proteolysis (E3 ubiquitinase system).

Seasonal sediment phosphorus release across sediment-water interface and its potential role in supporting algal blooms in a large shallow eutrophic Lake (Lake Taihu, China).

Seasonal sediment internal phosphorus (P) release is known to affect annual algal blooms in eutrophic lakes. In this study, a year-long field investigation and laboratory sediment core incubation were conducted to study the relationship between sediment internal P cycling and algal growth in Lake Taihu. The results indicated that the concentrations of water total phosphorus (TP) and chlorophyll-a (Chla) correlated with seasonal temperature and were assumed to be caused by internal P release. From cold winter to warm seasons, sediment internal P (porewater P concentration and P flux) exhibits dynamic changes. Sediment porewater soluble reactive phosphorus (SRP) and its flux in the summer were approximately five times and eight times those during winter, respectively. The release of sediment mobile P in the summer decreases its concentration and can supply SRP for algal blooms. Laboratory core incubation indicated that Chla and phycocyanin concentrations in the overlying water showed similar changes to sediment porewater P and P flux when cores were incubated from low to high temperature. The results of this study indicated that warmer conditions could increase the sediment porewater P concentration and sediment P flux into the bottom waters and consequently enhance sediment P availability to algae. This study provides new insights into the relationship between internal sediment P cycling and algal blooms in Lake Taihu.

[Network Meta-analysis of Qi-benefiting and blood-activating Chinese patent medicines against ischemic stroke].

This study aimed to compare the efficacy of Qi-benefiting and blood-activating Chinese patent medicines in the treatment of ischemic stroke with network Meta-analysis. CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Cochrane Library were searched from database inception to October 2022 for randomized controlled trial(RCT) on 11 Qi-benefiting and blood-activating Chinese patent medicines in the treatment of ischemic stroke. The risk of bias plot was made by RevMan 5.3, and network Meta-analysis and efficacy ranking were performed by Stata 17. Ninety-two RCTs were included, involving 10 608 patients. According to the network Meta-analysis, in terms of the clinical total effective rate, surface under the cumulative ranking curve(SUCRA) as followed: Qilong Capsules+conventional western medicine>Zhishe Tongluo Capsules+conventional western medicine>Longshengzhi Capsules+conventional western medicine>Naoxintong Capsules+conventional western medicine>Tongsaimai Tablets+conventional western medicine>Naoan Capsules+conventional western medicine>Naoluotong Capsules+conventional western medicine>Xiaoshuan Changrong Capsules+conventional western medicine>Dengzhan Shengmai Capsules+conventional western medicine=Tongxinluo Capsules+conventional western medicine>Naomaitai Capsules+conventional western medicine. In terms of the improvement in National Institute of Health stroke scale(NIHSS) score, SUCRA as followed: Longshengzhi Capsules+conventional western medicine>Naomaitai Capsules+conventional western medicine>Naoxintong Capsules+conventional western medicine>Dengzhan Shengmai Capsules+conventional western medicine>Xiaoshuan Changrong Capsules+conventional western medicine>Naoluotong Capsules+conventional western medi-cine>Tongxinluo Capsules+conventional western medicine>Naoan Capsules+conventional western medicine>Qilong Capsules+conventional western medicine. In terms of safety, the overall adverse reactions/events of Qi-benefiting and blood-activating Chinese patent medicines + conventional western medicine were less than those of the control group. Since Qilong Capsules+conventional western medicine and Zhishe Tongluo Capsules+conventional western medicine were preferred to improve the clinical total effective rate. In the aspect of improving NIHSS score, Longshengzhi Capsules+conventional western medicine and Naomaitai Capsules+conventional western medicine were first options. Due to the lack of direct comparisons between drugs, the overall quality of RCT was not high, so more studies are needed to verify the strength of the evidence.

[Acupoint selection rules of acupuncture and moxibustion for post-stroke epilepsy based on data mining technology].

OBJECTIVE: To analyze the acupoint selection rules of acupuncture and moxibustion for post-stroke epilepsy by data mining technology. METHODS: The literature regarding acupuncture and moxibustion for post-stroke epilepsy included in CNKI, VIP, Wanfang, SinoMed and PubMed databases from the establishment of the database to August 1st 2022 was retrieved. Microsoft Excel 2019 software was used to establish a database to conduct the descriptive analysis of acupoints; SPSS Modeler 18.0 Apriori algorithm was used to conduct association rule analysis; high-frequency acupoint co-occurrence network diagrams were drawn by Cytoscape3.9.0 software; SPSS Statistics 25.0 software was used to perform hierarchical cluster analysis on high-frequency acupoints and a tree diagram was drawn. RESULTS: Totally 39 articles were included, and 63 prescriptions of acupuncture and moxibustion were extracted, involving 56 acupoints, with a total frequency of 516 times; the top three acupoints with the highest frequency of use were Baihui (GV 20), Fenglong (ST 40) and Neiguan (PC 6); the selected meridians were mainly the governor vessel, the hand and foot yangming meridians; the selection of acupoints were mostly in the head, neck and lower limbs; in terms of acupoint compatibility, Hegu (LI 4)-Shuigou (GV 26) and Neiguan (PC 6) had the highest confidence degree; The top 20 high-frequency acupoints could be divided into 4 effective clusters. CONCLUSION: Modern acupuncture and moxibustion treatment for post-stroke epilepsy attaches great importance to the use of yang meridians and meridians with enrich qi and blood; the core prescription is Shuigou (GV 26)-Neiguan (PC 6)-Hegu (LI 4)-Baihui (GV 20). In addition, the combination of distant and near acupoints is highly valued to improve clinical efficacy.

Concurrent chemoradiotherapy followed by adjuvant cisplatin-gemcitabine versus cisplatin-fluorouracil chemotherapy for N2-3 nasopharyngeal carcinoma: a multicentre, open-label, randomised, controlled, phase 3 trial.

BACKGROUND: Patients with N2-3 nasopharyngeal carcinoma have a high risk of treatment being unsuccessful despite the current practice of using a concurrent adjuvant cisplatin-fluorouracil regimen. We aimed to compare the efficacy and safety of concurrent adjuvant cisplatin-gemcitabine with cisplatin-fluorouracil in N2-3 nasopharyngeal carcinoma. METHODS: We conducted an open-label, randomised, controlled, phase 3 trial at four cancer centres in China. Eligible patients were aged 18-65 years with untreated, non-keratinising, stage T1-4 N2-3 M0 nasopharyngeal carcinoma, an Eastern Cooperative Oncology Group performance status score of 0-1, and adequate bone marrow, liver, and renal function. Eligible patients were randomly assigned (1:1) to receive concurrent cisplatin (100 mg/m2 intravenously) on days 1, 22, and 43 of intensity-modulated radiotherapy followed by either gemcitabine (1 g/m2 intravenously on days 1 and 8) and cisplatin (80 mg/m2 intravenously for 4 h on day 1) once every 3 weeks or fluorouracil (4 g/m2 in continuous intravenous infusion for 96 h) and cisplatin (80 mg/m2 intravenously for 4 h on day 1) once every 4 weeks, for three cycles. Randomisation was done using a computer-generated random number code with a block size of six, stratified by treatment centre and nodal category. The primary endpoint was 3-year progression-free survival in the intention-to-treat population (ie, all patients randomly assigned to treatment). Safety was assessed in all participants who received at least one dose of chemoradiotherapy. This study was registered at ClinicalTrials.gov, NCT03321539, and patients are currently under follow-up. FINDINGS: From Oct 30, 2017, to July 9, 2020, 240 patients (median age 44 years [IQR 36-52]; 175 [73%] male and 65 [27%] female) were randomly assigned to the cisplatin-fluorouracil group (n=120) or cisplatin-gemcitabine group (n=120). As of data cutoff (Dec 25, 2022), median follow-up was 40 months (IQR 32-48). 3-year progression-free survival was 83·9% (95% CI 75·9-89·4; 19 disease progressions and 11 deaths) in the cisplatin-gemcitabine group and 71·5% (62·5-78·7; 34 disease progressions and seven deaths) in the cisplatin-fluorouracil group (stratified hazard ratio 0·54 [95% CI 0·32-0·93]; log rank p=0·023). The most common grade 3 or worse adverse events that occurred during treatment were leukopenia (61 [52%] of 117 in the cisplatin-gemcitabine group vs 34 [29%] of 116 in the cisplatin-fluorouracil group; p=0·00039), neutropenia (37 [32%] vs 19 [16%]; p=0·010), and mucositis (27 [23%] vs 32 [28%]; p=0·43). The most common grade 3 or worse late adverse event (occurring from 3 months after completion of radiotherapy) was auditory or hearing loss (six [5%] vs ten [9%]). One (1%) patient in the cisplatin-gemcitabine group died due to treatment-related complications (septic shock caused by neutropenic infection). No patients in the cisplatin-fluorouracil group had treatment-related deaths. INTERPRETATION: Our findings suggest that concurrent adjuvant cisplatin-gemcitabine could be used as an adjuvant therapy in the treatment of patients with N2-3 nasopharyngeal carcinoma, although long-term follow-up is required to confirm the optimal therapeutic ratio. FUNDING: National Key Research and Development Program of China, National Natural Science Foundation of China, Guangdong Major Project of Basic and Applied Basic Research, Sci-Tech Project Foundation of Guangzhou City, Sun Yat-sen University Clinical Research 5010 Program, Innovative Research Team of High-level Local Universities in Shanghai, Natural Science Foundation of Guangdong Province for Distinguished Young Scholar, Natural Science Foundation of Guangdong Province, Postdoctoral Innovative Talent Support Program, Pearl River S&T Nova Program of Guangzhou, Planned Science and Technology Project of Guangdong Province, Key Youth Teacher Cultivating Program of Sun Yat-sen University, the Rural Science and Technology Commissioner Program of Guangdong Province, and Fundamental Research Funds for the Central Universities.