Rules of acupoint selection in treatment of inflammatory bowel disease with acupuncture-moxibustion based on complex network analysis. / åŸºäºŽå¤æ‚ç½‘ç»œåˆ†æžé’ˆç¸æ²»ç–—ç‚Žæ€§è‚ ç— çš„é€‰ç©´è§„å¾‹.

OBJECTIVES: To analyze the rules of acupoint selection and compatibility of acupuncture and moxibustion in treatment of inflammatory bowel disease (IBD) based on complex network technology and provide the reliable evidences for acupoint selection in treatment of this disease with acupuncture and moxibustion. METHODS: The clinical studies on acupuncture-moxibustion treatment of IBD were searched from the databases including CNKI, Wanfang, VIP, PubMed and Embase. The studies were screened and the acupoint prescriptions were extracted to set up the database of acupuncture-moxibustion treatment for IBD. Using Microsoft Excel 2021 software, the use times of acupoint, the use frequency (%) of acupoint, meridian tropism and the use of special point were imported. With SPSS Modeler 18.0 software adopted, the association rules were analyzed on the acupoint prescriptions. The acupoint co-occurrence network diagram, k-core network diagram, and community analysis diagram were drawn by Gephi 0.9.5 software. RESULTS: A total of 156 studies were included, composed of 175 acupoint prescriptions, 75 acupoints, with 1 378 use times in total and around 8 acupoints in one prescription. Regarding the top use frequency, Tianshu (ST25), Zusanli (ST36), Guanyuan (CV4), Zhongwan (CV12) and Pishu (BL20) were listed. The top meridians involved were the foot-yangming stomach meridian, the foot-taiyang bladder meridian and the Conception Vessel. The front-mu point had been used with the highest frequency among the special points. ST36 and ST25 were a pair of points with the highest frequency in treatment. The k-core hierarchical analysis was adopted to optimize acupoint prescriptions, and 22 core acupoints were obtained, i.e. ST25, ST36, CV4, CV12, BL20, Dachangshu (BL25), Shangjuxu (ST37), Shenshu (BL23), Qihai (CV6), Sanyinjiao (SP6), Mingmen (GV4), Xingjian (LR2), Yinlingquan (SP9), Neiting (ST44), Taichong (LR3), Xiajuxu (ST39), Shuifen (CV9), Shenque (CV8), Ganshu (BL18), Weishu (BL21), Hegu (LI4) and Quchi(LI11), which were classified into three core acupoint groups by community analysis. CONCLUSIONS: Through complex network analysis, it is found that the local acupoints on the chest and abdomen are generally selected in treatment with acupuncture-moxibustion for IBD, the combination of the nearby and distal points is considered simulta-neously, and the acupoint prescription is modified according to syndrome/pattern differentiation；and among special points, the front-mu point is widely used in treatment. All of these rules provide the ideas for the acupoint selection of acupuncture-moxibustion in treatment of IBD.

Curculigoside, a traditional Chinese medicine monomer, ameliorates oxidative stress in Alzheimer's disease mouse model via suppressing ferroptosis.

Alzheimer's disease (AD) is a neurodegenerative disorder where oxidative stress, induced by ferroptosis, has been linked to neuronal damage and cognitive deficits. The objective of this study is to investigate if the potential therapeutic agent, Curculigoside (CUR), could ameliorate AD by inhibiting ferroptosis. The potential therapeutic targets, such as GPX4 and SLC7A11, were identified using weighted gene co-expression network analysis (WGCNA). Concurrently, CUR was also screened against these potential targets using various analytical methods. For the in vivo studies, intragastric administration of CUR significantly ameliorated cognitive impairment in AD model mice induced by scopolamine and okadaic acid (OA). In vitro, CUR protected neuronal cells by altering the levels of ferroptosis-related specific markers in OA and scopolamine-induced neurotoxicity. The administration of CUR through intragastric route significantly reduced the levels of AD-promoting factors (such as Aß1-42, p-tau) and ferroptosis-promoting factors in the hippocampus and cortex of AD mice. Furthermore, CUR up-regulated the expression of GPX4 and decreased the expression of SLC7A11 in the ferroptosis signaling pathway, thereby increasing the ratio of glutathione (GSH)/oxidized glutathione (GSSG) in vivo and vitro. In conclusion, the cumulative results suggest that the natural compound CUR may serve as a promising therapeutic agent to ameliorate AD by inhibiting ferroptosis.

Comprehensive effects of climate, land use/cover and management practices on runoff and nutrient variations in a rapidly urbanizing watershed.

As non-point source pollution has emerged as a significant global and regional concern, climate change (CC), land use/cover transformation (LUCT), and management practices (MP) play vital roles in addressing nutrient pollution. However, current studies lack comprehensive quantification and consistent conclusions on the response to these factors, especially for management practices. To quantify and elucidate the impact of representative environmental factors on rapidly urbanizing regions, this study focused on the Shenzhen River, which serves as the most typical urbanizing watershed. Using a process-based distributed hydrological model with a factor-controlled simulation method, we identified significant differences in nutrient concentrations and the impacts of climate variability, land use/cover changes, and anthropogenic interventions from 2003 to 2020. Moreover, effective measures greatly improved water quality in the Shenzhen River during study period, as evident from trend and cluster analysis. However, ecological water supplements implemented since 2016 have led to a slight reduction in simulated runoff performance, and CC may amplify the synergistic effects of precipitation and temperature on the river system. While the implemented practices have been effective in reducing total nitrogen (TN) and total phosphorus (TP) loads, strong TN pollution control is still needed in rapidly urbanizing areas due to the results of land use/cover type changes. Our findings emphasize the intricate interplay among CC, LUCT, and MP in shaping water quality and hydrological processes in rapidly urbanizing watersheds, and clarify the independent effects of these factors on nutrients. This study contributes to a better understanding of the complex interactions between multiple factors in watersheds and provides guidance for sustainable watershed management.

NGF/PI3K/TRPV1 pathway mediates the regulation of visceral pain by acupuncture at "Shangjuxu" (ST37) in irritable bowel syndrome rats with chronic visceral hyperalgesia. / NGF/PI3K/TRPV1通路介导针刺"上巨虚"è°ƒèŠ‚è‚ æ˜“æ¿€ç»¼åˆå¾æ ¢æ€§å† è„ç—›æ•æ¨¡åž‹å¤§é¼ å† è„ç—›.

OBJECTIVES: To investigate the effect of manual acupuncture at "Shangjuxu"(ST37) on nerve growth factor(NGF)/phosphatidylinositol 3-kinase(PI3K)/transient receptor potential vanilloid 1(TRPV1) signaling pathway in rats with chronic visceral hyperalgesia of irritable bowel syndrome (IBS), so as to explore its underlying mechanism in treating IBS chronic visceral hyperalgesia. METHODS: IBS chronic visceral hyperalgesia model was established by colorectal dilation stimulation for 2 weeks for SD pups at 8 d after birth, which were fed until 8-week age after the stimulation. Then the verified successfully modeled adult rats were randomly divided into model, Shangjuxu, and non-acupoint groups, with 6 rats in each group, and 6 unmodeled rats were selected as normal group. On the next day of model evaluation, rats in the Shangjuxu group received acupuncture at right ST37 while rats in the non-acupoint group received acupuncture at the non-meridian and non-acupoint point in the right hypochondrium, both for 15 min, with manual twisting of mild reinforcing and reducing performed for 30 s at an interval of 5 min, once a day, for a total of 7 d. Abdominal withdrawal reflex(AWR) score was used to evaluate the degree of chronic visceral pain in rats. Western blot and real-time fluorescence quantitative PCR were used to detect the colonic protein and mRNA expressions of NGF, tropomyosin receptor kinase A (TrkA), PI3K and TRPV1. The positive expressions of PI3K and TRPV1 proteins in the colon of rats were detected by immunohistochemistry method. RESULTS: Compared with the normal group, AWR scores corresponding to 4 pressure levels of 20, 40, 60 and 80 mm Hg, mRNA and protein expressions of NGF, TrkA, PI3K and TRPV1 in colon tissue, and positive expressions of PI3K and TRPV1 in colon tissue were significantly increased(P<0.05) in the model group. After intervention, compared with the model group, rats in the Shangjuxu group had reduced AWR scores corresponding to 4 pressure levels of 20, 40, 60 and 80 mm Hg, lower colonic mRNA and protein expressions of NGF, TrkA, PI3K and TRPV1, and decreased positive expressions of PI3K and TRPV1 in colon tissue(P<0.05), while there were no significant differences in the above indexes of the non-acupoint group. CONCLUSIONS: Manual acupuncture at ST37 can alleviate IBS chronic visceral hyperalgesia in rat and its analgesic effect may be related to regulating NGF/PI3K/TRPV1 signaling pathway.

Multi-scenario simulation of runoff and nutrient loads in a rapidly urbanizing watershed during China's Dual Carbon periods.

Apprehending the hydrological and nutrient variations in rapidly urbanizing watersheds under changing environments is crucial for pollution control and water resource management. However, existing studies have primarily focused on hydrological processes, neglecting water quality aspects, and comprehensive assessment of future runoff and nutrient loads in these watersheds during China's Dual Carbon periods is limited. This study firstly bridges these gaps by constructing multi-scenario with different levels of "Urban Development - Ecological Conservation" and utilizing latest bias-corrected General Circulation Models or Global Climate Models (GCMs) projections to evaluate future runoff and nutrient loads in the Shenzhen River. The calibrated and validated models display satisfactory performance in simulating runoff, nutrient loads, and land use types. The bias-corrected GCMs projections exhibit enhanced accuracy for temperature variables, particularly during the wet season. Implementing effective ecological protection measures is paramount in mitigating water quantity fluctuations and controlling total nitrogen pollution, which is closely associated with urban development and human activities. Conversely, total phosphorus loads demonstrate greater simulation uncertainty, particularly during the dry season of the Carbon Neutrality period, requiring further exploration. Compared to the baseline period, runoff changes minimally, with notable seasonal variations. The findings highlight the escalating uncertainty in load predictions as time progresses. Additionally, addressing uncertainties in precipitation projections driven by GCMs is imperative, given their substantial influence on runoff and nutrient load simulations, particularly during challenging dry seasons. While further research is needed to reduce simulation uncertainty, our study provides valuable insights into nitrogen-phosphorus pollution control and sustainable water resource management in rapidly urbanizing watersheds, especially during the near-term period.

Assessing water quality in the Pearl River for the last decade based on clustering: Characteristic, evolution and policy implications.

The Pearl River (PR) is China's second-largest river, playing a crucial role in regulating and supplying water in the southeast. However, for the last decade, the PR has been experiencing water quality deterioration due to population growth, rapid economic development, and diverse human activities, particularly in its delta areas. This study analyzed the characteristics and evolution of eight water quality variables, including pH values (pH), water temperature (WT), dissolved oxygen (DO), five-day biochemical oxygen demand (BOD5), permanganate index (PI), total phosphorus (TP), ammonia nitrogen (NH3N), and fluoride (F-), which were monitored monthly at 16 water quality monitoring stations from January 2009 to August 2019. Overall, annual average BOD5 and F- concentrations met Class I water quality standards, while TP and NH3N conformed to lower standards. The cluster results showed noticeable differences for parameter grouping (DO-organic parameters-nutrient and solutes), seasonal variation (wet and dry), and water quality status (contaminated-remediating-fine). The Water Quality Index (WQI) ranged from 8.3 ("very poor") to 91.7 ("excellent") in the entire basin from 2009 to 2019, and NH3N-DO based WQImins were identified using the All-Subsets Linear Regression method. The fitting results of the Generalized Additive Models displayed that the deviance explained by natural factors ranged from 37.2% to 61.3%, while the socioeconomic explanation exceeded 70%. The WQImin component evolution (2003-2019) of Shenzhen River estuary, the most important part of the PR estuary, agreed with key parameter variations in heterogeneous clusters in the entire basin. Moreover, Shenzhen's water quality remediation applications indicated that reasonable-efficient-powerful efforts and support from governments could accelerate recovery. For the management departments, consistent measures should be strictly enforced, and elaborate regionalized management based on clusters could be attempted to maintain excellent water quality.

A wireless physiological parameter monitoring system with a treatment feedback function during neonatal phototherapy.

Objective. Neonatal jaundice is a common condition in the early stages of newborns, and phototherapy is a fast, safe and effective method that is used to treat it. However, recent studies have shown that phototherapy may elicit side effects in infants, such as hypothermia, hyperthermia and dehydration. To improve the quality of phototherapy and the prognosis of patients, the changes in neonatal physiological parameters during phototherapy should be monitored to give better feedback to pediatricians or the phototherapy system. However, the current standard of clinical care during neonatal phototherapy with hard-wired devices limits this realization.Approach. Here, we developed a prototype of a neonatal wearable device, which can wirelessly potentially monitor the jaundice value, transepidermal water loss, skin wettedness factor and body orientation during phototherapy, and conducted prototype validation experiments. We also set up user-friendly interfaces and an analysis system on custom software, all designed to make the future addition of data interfaces for treatment feedback functions easier.Main results. The preliminaryin vitroexperiment demonstrated the effectiveness of simultaneous monitoring of the required physiological parameters. And further suggestions and specific operations are discussed in terms of optimization of the treatment of neonatal jaundice.Significance. It is believed that the established system has the potential to provide a basis for future phototherapy nursing guidelines and physiological monitoring standards.

Inhibition of cell wall pectin metabolism by plasma activated water (PAW) to maintain firmness and quality of postharvest blueberry.

Blueberry is a class of berries with high nutritional and economic value but has short shelf life due to its rapid softening at room temperature. This study investigated the effects of plasma-activated water (PAW) treatment on the softening quality and cell wall pectin metabolism of blueberries stored for 10 d at 25 °C after being immersed in PAW for 10 min. PAW was generated by plasma with different times (1 and 2 min), fixed frequency (10 kHz) and fixed voltage (50 kV). The analysis showed that the firmness of PAW-treated fruit significantly increased (P < 0.05) by 36.4% after 10 d storage. PAW treatment controlled the solubilization of pectin from water-insoluble to water-soluble. The activities of cell wall pectin-degrading enzymes like polygalacturonase (PG), ß-galactosidase (ß-Gal) and pectin methylesterase (PME) in PAW-treated blueberries decreased by 15.7%, 18.3%, and 27.9%, respectively, on day 10. After PAW treatment, blueberries also maintained better postharvest quality (firmness, colour, soluble solid content and anthocyanin content) and intact epidermal waxy and cell wall structure. These results suggested that PAW showed great potential for postharvest fresh-keeping of blueberry.

[Effect of transcutaneous electrical acupoint stimulation on learning and memory ability of chronic fatigue syndrome rats and its mechanisms].

OBJECTIVE: To observe the effect of transcutaneous electrical acupoint stimulation (TEAS) on the histomorphological manifestations of hippocampal CA1 region and the expression of extracellular regulatory protein kinase (ERK), cyclic adenosine response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in chronic fatigue syndrome (CFS) rats, so as to explore the mechanisms of TEAS in improving the learning and memory abilities of CFS rats. METHODS: Forty male Wistar rats were randomly divided into normal group (10 rats) and modeling group (30 rats); then after modeling, they were selected and randomly divided into model group (10 rats) and TEAS group (10 rats). CFS rats model was prepared by sleep deprivation combined with weight-bearing swimming. Rats in the TEAS group were stimulated with Han's acupoint nerve stimulator at bilateral "Zusanli" (ST36) and "Shenshu" (BL23) (2 Hz/15 Hz, 1-2 mA), 20 min each time, once a day for 4 weeks with 1 d rest every 6 d. The score of general conditions of rats was evaluated. The learning and memory ability was tested with Morris water maze. The morphology and ultrastructure of hippocampal CA1 region were observed by HE staining and transmission electron microscopy. The expression levels of ERK, CREB and BDNF mRNAs and proteins in hippocampus were detected by real time quantitative PCR and Western blot, respectively. RESULTS: Compared with the normal group, the score of general condition was increased (P<0.01); the escape latency was prolonged (P<0.05, P<0.01) and the times of crossing the original platform was decreased (P<0.05); the expression levels of ERK, CREB and BDNF mRNAs and proteins in hippocampus were decreased (P<0.05, P<0.01) in the model group. Compared with the model group, the scores of general condition on the 42nd and 49th day were decreased (P<0.05, P<0.01); the escape latency was shortened (P<0.01, P<0.05)and the times of crossing the original platform were increased (P<0.05); the expression levels of ERK, CREB and BDNF mRNAs and proteins in hippocampus were increased (P<0.01, P<0.05) in the TEAS group. The morphology of neurons in hippocampal CA1 region was normal in the normal group. In the model group, the number of neurons in hippocampal CA1 region decreased, the arrangement of nerve cells was scattered, the number of apoptotic cells increased, some nuclear structures disappeared, nuclear heterochromatin increased, the cell membrane wrinkled, the chromatin appeared empty bright area, and the crista was incomplete. Compared with the model group, the nerve cells morphology in hippocampal CA1 region was more regular, the number of apoptotic cells decreased, the chromatin and the cytoplasm were uniformly distributed, and the crista was relatively intact in the TEAS group. CONCLUSION: TEAS can improve the learning and memory ability of CFS rats, the mechanisms may be related to improving the neural structure of hippocampal CA1 region and up-regulating the expression levels of ERK/CREB/BDNF.

[The rules of acupoint selection of acupuncture and moxibustion for aphasia based on data mining].

OBJECTIVE: To explore the rules of acupoint selection for aphasia treated with acupuncture and moxibustion using data mining technology. METHODS: From January 1, 2000 to April 1, 2022, the articles for clinical researches of acupuncture and moxibustion for aphasia published in CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase were searched. Using Microsoft Excel 2021, the database was set up to analyze the use frequency of acupoint, meridian tropism, acupoint distribution and the use of specific points. SPSS26.0 was adopted for factor analysis, SPSS Modeler 18.0 was for association rule analysis of prescriptions, and Gephi 0.9.5 was to plot the co-occurrence network diagrams of acupoints and meridians. RESULTS: A total of 140 articles were collated, including 146 acupuncture and moxibustion prescriptions and 189 acupoints. The total use frequency of these acupoints was 1 211. Lianquan (CV 23), Jinjin (EX-HN 12), Yuye (EX-HN 13), Baihui (GV 20) and Yamen (GV 15) were the top 5 acupoints of the high use frequency for aphasia treated with acupuncture and moxibustion. Among 189 acupoints collected, the extra points and empirical points were mostly selected. The top 3 involved meridians were the governor vessel, the gallbladder meridian of foot-shaoyang and the conception vessel. These acupoints were mostly distributed on the head, face and neck region. The use frequency of five-shu points was the highest among the specific points. The acupoint combinations of high frequency referred to Yuye (EX-HN 13)-Jinjin (EX-HN 12), Yuye (EX-HN 13)-Lianquan (CV 23)-Jinjin (EX-HN 12), and Fengchi (GB 20)-Yuye (EX-HN 13)-Jinjin (EX-HN 12). Factor analysis extracted 10 common factors for acupoint compatibility in treatment of aphasia with acupuncture and moxibustion. CONCLUSION: In clinical treatment of aphasia with acupuncture and moxibustion, the local acupoints are preferred. The core acupoints include Lianquan (CV 23), Jinjin (EX-HN 12), Yuye (EX-HN 13), Baihui (GV 20) and Yamen (GV 15). The acupoint prescription is modified flexibly according to syndrome differentiation to enhance the therapeutic effect.

Investigation of Naoluoxintong on the neural stem cells by facilitating proliferation and differentiation in vitro and on protecting neurons by up-regulating the expression of nestin in MCAO rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The classic traditional Chinese compound Naoluoxintong (NLXT) has been proven an effective remedy for ischemic stroke (IS). The protective effect of NLXT on neural stem cells (NSCs), however, remains unclear. AIM OF THE STUDY: To investigate the protective effect of NLXT on NSCs in rats with middle cerebral artery occlusion (MCAO) and the effect of Nestin expression in vivo. MATERIALS AND METHODS: Sprague-Dawley (SD) rats were randomly divided into three groups: the sham-operated group, the MCAO model group and the NLXT group. The MCAO model in rats was established by modified Longa wire embolization method. The sham-operated group, the model group and the NLXT groups were divided into three subgroups according to the sampling time points of 1 d, 3 d and 7 d after successful model-making. Immunofluorescence staining, including bromodeoxyuridine (BrdU)/glial fibrillary acidic protein (GFAP), ß-tubulinIII/GFAP, BrdU/doublecortin (DCX) and BrdU/neuronal nuclei (NeuN), was used to detect the proliferation and survival of NSCs in the hippocampal after drug administration. Protein expression of Nestin, DCX, GFAP and NeuN in the hippocampal was detected by Western blot (WB). RESULTS: Immunofluorescence experiment of Nestin labeled: on the first day, a few Nestin-positive cells were found in the hippocampal DG area. Afterwards, the number of Nestin-labeled positive cells in the model group increased, while the number of cells in the sham group did not fluctuate significantly. The number of positive cells in each administration group increased more than that in the model and normal group. ß-tubulin III/GFAP double-labeled: a small amount of double labeled cells was expressed in the normal group, and the number subsequently fluctuated little. In the model group, ß-tubulin III/GFAP positive cells increased initially after acute ischemia, and gradually decreased afterwards. In the NLXT-treated group, ß-Tubulin III positive cells were significantly increased on day 1, 3 and 7, while GFAP positive cells had little change. BrdU/DCX double-labeled: initially, a small number of BrdU/DCX-labeled positive cells were observed in the normal group and the model group, but there was no increasing trend over time. The positive cells in the NLXT group increased over time, and those in the seven-day group were significantly higher than those in the one-day and three-day groups. BrdU/NEUN double-labeled: in the normal group, BrdU/NEUN positive cells were enriched and distributed regularly. The number of positive cells in the model group was small and decreased gradually with time, and the decrease was most obvious on the third day. The number of positive cells in the NLXT group was significantly higher than that in the model group, and the number of positive cells in the seven-day group was significantly higher than that in the one-day and three-day groups. WB results reflected those three proteins, Nestin, NeuN and DCX, showed an increase in expression, except GFAP, which showed a decreasing trend. CONCLUSIONS: Preliminarily, NLXT can promote the migration and differentiation of NSCs. It may have a protective effect on the brain by promoting repair of brain tissue damage through upregulation of Nestin after IS.

Association between Vitamin D Supplementation and Cancer Mortality: A Systematic Review and Meta-Analysis.

BACKGROUND: Vitamin D deficiency is related to increased cancer risk and deaths. However, whether vitamin D supplementation reduces cancer mortality remains unclear, and several randomized controlled trials yield inconsistent results. METHODS: Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched from their inception until 28 June 2022, for randomized controlled trials investigating vitamin D supplementation. Pooled relative risks (RRs) and their 95% confidence intervals (CIs) were estimated. Trials with vitamin D supplementation combined with calcium supplementation versus placebo alone and recruiting participants with cancer at baseline were excluded in the present study. RESULTS: This study included 12 trials with a total of 72,669 participants. Vitamin D supplementation did not reduce overall cancer mortality (RR 0.96, 95% CI 0.80-1.16). However, vitamin D supplementation was associated with a reduction in lung cancer mortality (RR 0.63, 95% CI 0.45-0.90). CONCLUSIONS: Vitamin D supplementation could not reduce cancer mortality in this highly purified meta-analysis. Further RCTs that evaluate the association between vitamin D supplementation and total cancer mortality are still needed.

Parallel CD19/CD20 CAR-Activated T-Cells Are More Effective for Refractory B-Cell Lymphoma In Vitro and In Vivo.

Anti-CD19 chimeric antigen receptor (CAR) T-cells are an effective treatment for refractory B-cell lymphoma, but CD19 deletion is prone to relapse. We conducted this study to find more effective dual CAR19/20 T-cells to target B-cell lymphoma and prevent antigen loss leading to recurrence. In this study, we transduced CD19 and CD20 CARs into human T cells in parallel and compared parallel dual CAR19/20, single CAR, and tandem CAR19/20 in vitro and in vivo. After transduction with the corresponding vectors, CD19 and CD20 CARs were dually expressed in human T cells. It was observed that parallel CAR19/20 T-cells contained a substantial proportion of naive subpopulations and were able to proliferate in vitro. Treatment with parallel CAR19/20, single CAR, or tandem CAR19/20 T-cells sustainably induced complete lysis of leukemia cells in a 5 : 1 ratio. Compared with single or tandem CAR T-cell-transplanted mice, parallel CAR19/20 T-cell-transplanted mice exhibited smaller tumor volume, more stable body weight, and longer survival. This suggests that parallel CAR19/20 has superior antilymphoma activity in vivo. In addition, parallel CAR19/20 T-cells were also able to kill patients' lymphoma cells in vitro. Therefore, it can be considered that parallel CAR19/20 is equally effective against single CAR and tandem CAR19/20 in vitro but more effective against lymphoma cells in vivo. This is a promising treatment to prevent the recurrence of antigen loss following CD19-targeted therapy in B lymphoma.

Naoluo Xintong Decoction in the Treatment of Ischemic Stroke: A Network Analysis of the Mechanism of Action.

The mechanism of action of Naoluo Xintong decoction (NLXTD) for the treatment of ischemic stroke (IS) is unknown. We used network analysis and molecular docking techniques to verify the potential mechanism of action of NLXTD in treating IS. The main active components of NLXTD were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and IS targets were collected from the Online Mendelian Inheritance in Man (OMIM), GeneCards, and Drugbank databases; their intersection was taken. In addition, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed and used to build protein-protein interaction networks. AutoDock Vina software was used for molecular docking, and animal experiments were conducted to verify the results. Hematoxylin and eosin staining was used to observe the brain morphology of rats in each group, and real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression level of relative mRNA in the brain tissue of rats. Western blot was used to detect the expression level of relative protein in the brain tissue of rats. Network analysis and molecular docking results showed that CASP3, NOS3, VEGFA, TNF, PTGS2, and TP53 are important potential targets for NLXTD in the treatment of IS. RT-qPCR and western blot results showed that NLXTD inhibited the expression of CASP3, TNF, PTGS2, and TP53 and promoted the expression of VEGFA and NOS3. NLXTD treats IS by modulating pathways and targets associated with inflammation and apoptosis in a multicomponent, multitarget manner.

Optimization of Ultrasonic-Assisted Extraction of Total Flavonoids from Abrus Cantoniensis (Abriherba) by Response Surface Methodology and Evaluation of Its Anti-Inflammatory Effect.

Abrus cantoniensis is a Chinese herbal medicine with efficacy in clearing heat and detoxification, as well as relieving liver pain. The whole plant, except the seeds, can be used and consumed. Flavonoids have been found in modern pharmacological studies to have important biological activities, such as anti-inflammatory, antibacterial and antioxidant properties. The antibacterial and antioxidant bioactivities of the total flavonoids of Abrus cantoniensis (ATF) have been widely reported in national and international journals, but there are fewer studies on their anti-inflammatory effects. The present study focused on the optimization of the ultrasonic extraction process of ATF by response surface methodology and the study of its anti-inflammatory effects in vitro and in vivo. The results showed that the factors that had a great impact on the ATF extraction were the material-to-liquid ratio, ultrasonic extraction cycles and ethanol concentration. The best extraction process used a material-to-liquid ratio of 1:47, ultrasonic extraction cycles of 4 times, an ethanol concentration of 50%, an ultrasonic extraction time of 40 min and an ultrasonic power of 125 W. Under these conditions, the actual extraction rate of total flavonoids was 3.68%, which was not significantly different from the predicted value of 3.71%. In an in vitro anti-inflammatory assay, ATF was found to be effective in alleviating LPS (lipopolysaccharide)-induced inflammation in mouse peritoneal macrophages. In an in vivo anti-inflammatory assay, ATF was found to have a significant inhibitory effect on xylene-induced ear swelling in mice and cotton ball granuloma in mice, and the inhibitory effect was close to that of the positive control drug dexamethasone. This may provide a theoretical basis for the further development of the medicinal value of Abrus cantoniensis.

Naoluo Xintong Decoction Ameliorates Cerebral Ischemia-Reperfusion Injury by Promoting Angiogenesis through Activating the HIF-1α/VEGF Signaling Pathway in Rats.

Background: Naoluo Xintong decoction (NLXTD) is a traditional Chinese medicine (TCM) formula which has been used to improve neuronal functional recovery after cerebral ischemic stroke. However, the molecular mechanism underlying NLXTD's amelioration of ischemic stroke remains unclear. The present study was designed to explore the effect and mechanism of NLXTD on brain angiogenesis in a rat model with cerebral ischemia-reperfusion (I/R) injury targeting the hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) pathway. Materials and Methods: Cerebral I/R model was established by the classical middle cerebral artery occlusion (MCAO) method. Sprague-Dawley (SD) male rats (n = 80) were randomly divided into the sham-operation group, the model group, the HIF-1α inhibitor 2-methoxyestradiol (2ME2) group, the 2ME2 with NLXTD group, and the NLXTD group. Neurological deficit test, TTC staining, H&E staining, TUNEL staining, immunohistochemistry (IH), immunofluorescence (IF), western blot, and quantitative RT-PCR were performed to evaluate the effect of NLXTD after MCAO. Results: Administration of NLXTD significantly decreased neuron deficiency scores, reduced brain infarct volume, and lowered damaged and apoptotic cells after brain I/R injury in rats. Meanwhile, NLXTD had a protective effect on angiogenesis by increasing the MVD and the expressions of BrdU and CD34, which enhanced the number of endothelial cells in the ischemic penumbra brain. NLXTD treatment significantly raised the protein and mRNA levels of HIF-1α, VEGF, VEGFR2, and Notch1 compared with the model treatment. In contrast, a specific HIF-1α inhibitor, 2ME2, inhibited the improvement of neurological function and angiogenesis in NLXTD-induced rats with cerebral I/R injury, suggesting that NLXTD played a positive role in ischemic brain injury by activating the HIF-1α/VEGF signaling pathway. Conclusions: NLXTD exerts neuroprotection targeting angiogenesis by upregulating the HIF-1α/VEGF signaling pathway on cerebral I/R injury rats.

Isolation and Characterization of Natural Nanoparticles in Naoluo Xintong Decoction and Their Brain Protection Research.

Currently, researchers use modern analytical techniques in a unique perspective of physical pharmacy to analyze the phase composition of traditional Chinese medicine (TCM) and have discovered that natural nanoparticles commonly exist in decoctions. This study aims to isolate and characterize the structure and composition of nanoparticles in Naoluo Xintong (NLXT) and investigate whether the brain protection effect of NLXT is closely related to NLXT-Nanoparticles (NLXT-NPs). Firstly, the dialysis-centrifugation method was used to separate the nanoparticles and then their size distribution, potential, and morphology were characterized. In addition, infrared spectroscopy and ultra-high performance liquid chromatography-quadrupole-time of flight-mass spectrometer (UPLC-Q-TOF-MS) technology were used to analyze the composition of nanoparticles. As for the pharmacodynamic experiment, Sprague Dawley (SD) rats were randomly divided into sham, Middle cerebral artery occlusion (MCAO) model, NLXT, NLXT with nanoparticles removing (NLXT-RN), NLXT-RN+Nanoparticles (NLXT-RN+NPs), and NLXT-NPs groups. After administration, the neurological function, histopathological changes, oxidative stress, and apoptosis level were measured. Our research showed that NLXT-NPs are mainly composed of polysaccharides, proteins, and saponins, with typical characteristics of two hundred-nanometer size and negatively loaded. NLXT can improve nerve function, reduce oxidative stress, and inhibit cell apoptosis. However, removing nanoparticles can significantly reduce the brain-protective effect of NLXT, which indicates that NLXT-NPs play an essential role in the efficacy of NLXT.

Antipyretic Mechanism Exploration of HuanglianShangqing Pill Based on Metabolomics and Network Pharmacology.

BACKGROUND AND OBJECTIVE: HuanglianShangqing pill (HLSQ), a well-known traditional Chinese medicine (TCM), has been used to treat fever in China for a long time. Our previous study had demonstrated that a total of 45 prototype components of HLSQ could be absorbed into the plasma of rats after intragastric administration. However, the detailed mechanisms related to the antipyretic effects of HLSQ were still unclear. METHODS: In the present work, urinary metabolomics coupled with network pharmacology were employed to evaluate the mechanisms of HLSQ in the treatment of fever compared with ibuprofen (IBU) and paracetamol (APAP). RESULTS: In pyrexia rats, a total of 11 potential metabolites and a disturbed TCA cycle were found. The metabolic regulation effects of HLSQ on fever rats were similar to APAP and could make the TCA cycle disorder return to normal by reducing citrate, ß-hydroxybutyrate, succinate. In addition, HLSQ could adjust the intestinal microbial disorder and inhibit inflammatory factors, including IL6, TNF, VEGFA, TP53, STAT3, etc. There were 40 components acting on fever targets in HLSQ; among them, luteolin, apigenin, ursolic acid, kaempferol, wogonin, daidzein, baicalein, emodin, berberine, and oroxylin A were the main active compounds of HLSQ in the treatment of fever. CONCLUSION: The antipyretic mechanisms of HLSQ are inhibition of inflammatory factors, action on the TCA cycle, and regulation of gut microbiota.

Association between fish oil supplementation and cancer risk according to fatty fish consumption: A large prospective population-based cohort study using UK Biobank.

Whether regular fish oil supplementation is associated with cancer risk is controversial. We aimed to evaluate the association of fish oil supplementation on cancer risk according to fatty fish consumption patterns. From the UK Biobank cohort, 470 804 participants with fish oil supplementation data were included. A total of 147 316 individuals with fish oil supplementation were in the exposed group; the other 323 488 were in the unexposed group. No association was found between self-report regular fish oil supplementation and overall cancer risk (hazard ratio [HR] = 0.97, 95% confidence intervals [CIs] = 0.95-1). Stratified by fatty fish consumption level, we found the association between fish oil supplementation and lower cancer risk in participants who consumed fatty fish less than two times per week, with association noted for both overall cancer (HR = 0.96, 95% CI = 0.94-0.99) and some specific cancers (colon cancer: HR = 0.84, 95% CI = 0.75-0.94; hepatobiliary cancer: HR = 0.74, 95% CI = 0.58-0.96; lung cancer: HR = 0.87, 95% CI = 0.78-0.98). On the contrary, a higher risk of breast cancer was observed (HR = 1.16, 95% CI = 1.01-1.32) in participants who consumed fatty fish at least two times per week. In conclusion, our findings underscore the need to refine recommendations for nutritional supplements according to inherent diet habits.

Transcriptome and Metabolome Analyses Provide Insights into the Stomium Degeneration Mechanism in Lily.

Lily (Lilium spp.) is a widely cultivated horticultural crop that has high ornamental and commercial value but also the serious problem of pollen pollution. However, mechanisms of anther dehiscence in lily remain largely unknown. In this study, the morphological characteristics of the stomium zone (SZ) from different developmental stages of 'Siberia' lily anthers were investigated. In addition, transcriptomic and metabolomic data were analyzed to identify the differentially expressed genes (DEGs) and secondary metabolites involved in stomium degeneration. According to morphological observations, SZ lysis occurred when flower buds were 6-8 cm in length and was completed in 9 cm. Transcriptomic analysis identified the genes involved in SZ degeneration, including those associated with hormone signal transduction, cell structure, reactive oxygen species (ROS), and transcription factors. A weighted co-expression network showed strong correlations between transcription factors. In addition, TUNEL (TdT-mediated dUTP nick-end labeling) assays showed that programmed cell death was important during anther SZ degeneration. Jasmonates might also have key roles in anther dehiscence by affecting the expression of the genes involved in pectin lysis, water transport, and cysteine protease. Collectively, the results of this study improve our understanding of anther dehiscence in lily and provide a data platform from which the molecular mechanisms of SZ degeneration can be revealed.