Effects of traditional Chinese medicine on treatment outcomes in severe COVID-19 patients: a single-centre study.

As the search for effective treatments for COVID-19 continues, the high mortality rate among critically ill patients in Intensive Care Units (ICU) presents a profound challenge. This study explores the potential benefits of traditional Chinese medicine (TCM) as a supplementary treatment for severe COVID-19. A total of 110 critically ill COVID-19 patients at the Intensive Care Unit (ICU) of Vulcan Hill Hospital between Feb., 2020, and April, 2020 (Wuhan, China) participated in this observational study. All patients received standard supportive care protocols, with a subset of 81 also receiving TCM as an adjunct treatment. Clinical characteristics during the treatment period and the clinical outcome of each patient were closely monitored and analysed. Our findings indicated that the TCM group exhibited a significantly lower mortality rate compared with the non-TCM group (16 of 81 vs 24 of 29; 0.3 vs 2.3 person/month). In the adjusted Cox proportional hazards models, TCM treatment was associated with improved survival odds (P < 0.001). Furthermore, the analysis also revealed that TCM treatment could partially mitigate inflammatory responses, as evidenced by the reduced levels of proinflammatory cytokines, and contribute to the recovery of multiple organic functions, thereby potentially increasing the survival rate of critically ill COVID-19 patients.

pH/glutathione dual-responsive copper sulfide-coated organic mesoporous silica for synergistic chemo-photothermal therapy.

Nanodrug delivery systems (NDSs), such as mesoporous silica, have been widely studied because of their high specific surface area, high loading rate, and easy modification; however, they are not easily metabolized and excreted by the human body and may be potentially harmful. Hence, we aimed to examine the synergistic anti-tumor effects of ex vivo chemo-photothermal therapy to develop a rational and highly biocompatible treatment protocol for tumors. We constructed a biodegradable NDS using organic mesoporous silica with a tetrasulfide bond structure, copper sulfide core, and folic acid-modified surface (CuS@DMONs-FA-DOX-PEG) to target a tumor site, dissociate, and release the drug. The degradation ability, photothermal conversion ability, hemocompatibility, and in vitro and in vivo anti-tumor effects of the CuS@DMONs-FA-DOX-PEG nanoparticles were evaluated. Our findings revealed that the nanoparticles encapsulated in copper sulfide exhibited significant photothermal activity and optimal photothermal conversion rate. Further, the drug was accurately delivered and released into the target tumor cells, annihilating them. This study demonstrated the successful preparation, safety, and synergistic anti-tumor effects of chemo-photothermal therapeutic nanomaterials.

[Stapled anoplin peptide combined with photothermal therapy enhances oncolytic immunotherapy of triple-negative breast cancer].

This study constructed a nano-drug delivery system, A3@GMH, by co-delivering the stapled anoplin peptide(Ano-3, A3) with the light-harvesting material graphene oxide(GO), and evaluated its oncolytic immunotherapy effect on triple-negative breast cancer(TNBC). A3@GMH was prepared using an emulsion template method and its physicochemical properties were characterized. The in vivo and in vitro photothermal conversion abilities of A3@GMH were investigated using an infrared thermal imager. The oncoly-tic activity of A3@GMH against TNBC 4T1 cells was evaluated through cell counting kit-8(CCK-8), lactate dehydrogenase(LDH) release, live/dead cell staining, and super-resolution microscopy. The targeting properties of A3@GMH on 4T1 cells were assessed using a high-content imaging system and flow cytometry. In vitro and in vivo studies were conducted to investigate the antitumor mechanism of A3@GMH in combination with photothermal therapy(PTT) through inducing immunogenic cell death(ICD) in 4T1 cells. The results showed that the prepared A3@GMH exhibited distinct mesoporous and coated structures with an average particle size of(308.9±7.5) nm and a surface potential of(-6.79±0.58) mV. The encapsulation efficiency and drug loading of A3 were 23.9%±0.6% and 20.5%±0.5%, respectively. A3@GMH demonstrated excellent photothermal conversion ability and biological safety. A3@GMH actively mediated oncolytic features such as 4T1 cell lysis and LDH release, as well as ICD effects, and showed enhanced in vitro antitumor activity when combined with PTT. In vivo, A3@GMH efficiently induced ICD effects with two rounds of PTT, activated the host's antitumor immune response, and effectively suppressed tumor growth in 4T1 tumor-bearing mice, achieving an 88.9% tumor inhibition rate with no apparent toxic side effects. This study suggests that the combination of stapled anoplin peptide and PTT significantly enhances the oncolytic immunotherapy for TNBC and provides a basis for the innovative application of anti-tumor peptides derived from TCM in TNBC treatment.

[Electroacupuncture at "Baihui"（GV20） and "Yongquan"（KI1） improves learning-memory ability of APP/PS1 double transgenic mice by regulating endosomal-lysosomal system].

OBJECTIVE: To explore the mechanism of electroacupuncture（EA） in improving learning-memory ability in Alzheimer's disease （AD） mice from the perspective of endosomal-lysosomal system. METHODS: Male APP/PS1 transgenic mice were randomly divided into model group and EA group （n=10 in each group） and 10 male C57BL/6 wild mice were taken as the normal group. EA （1 Hz/50 Hz, 1 mA） was applied at bilateral "Yongquan"（KI1） and acupuncture was applied at "Baihui" （GV20） for 15 min. The mice of the model and normal groups were subjected to restriction with the same method as those of the EA group for 15 min. The treatment was conducted once every other day for 6 weeks. The spatial learning-memory ability （shown by escape latency of place navigation test and the time of crossing the target platform and total swimming distance in the target quadrant in 1 min of spatial probe test ） was detected by Morris water maze test. The immunoactivity of senile plaques （SP） in the hippocampus tissue was detected by immunohistochemistry. The ultrastructural characters of hippocampal neurons were observed by transmission electron microscope, and the expression levels of Ras-related protein 5 （Rab5）, Ras-related protein 7 （Rab7） and cathepsin D （CTSD） in the hippocampus were detected by Western blot, separately. RESULTS: Compared with the normal group, the escape latency, SP immunoactivity, and protein expression levels of Rab5, Rab7 and CTSD were significantly increased （P<0.05, P<0.01）, while the number of crossing the original platform and the total swimming distance in the platform quadrant were considerably reduced （P<0.05） in the model group. In contrast to the model group, the EA group had a marked decrease in the escape latency, SP immunoactivity, and protein expression levels of Rab5, Rab7 and CTSD （P<0.05, P<0.01）, and a striking increase in the number of crossing the original platform and the swimming distance in the platform quadrant （P<0.05）. Results of transmission electron microscope showed an accumulation of endosome, lysosome, and endolysosomes in the hippocampal neurons in the model group, which was evidently milder in the EA group. CONCLUSION: EA of GV20 and KI1 can improve the learning-memory ability of AD mice, which may be related to its function in reducing hippocampal Aß deposition and down-regulating endosomal-lysosomal system activity.

[Overview of systematic reviews of Chinese herbal injections for sepsis].

In this study, an overview of systematic reviews/Meta-analysis(SR/MA) of Chinese herbal injections for sepsis was performed to provide references for clinical practice and promote the quality improvement of clinical evidence. Eight Chinese and English databases such as CNKI, Medline, and EMbase were electronically searched for SR/MA of Chinese herbal injections for sepsis from database inception to June 2022. AMSTAR 2, PRISMA 2020, and GRADE system, combined with Recommendations for Clinical Evidence Grading on Traditional Chinese Medicine Based on Evidence Body, were applied to evaluate the methodological quality, reporting quality, and evidence quality of the included articles. Twenty-seven articles of SR/MA were included, containing four Chinese herbal injections(Xuebijing Injection, Shenfu Injection, Shenmai Injection, and Shengmai Injection). AMSTAR 2 checklist showed that the methodological quality of the SR/MA ranged from moderate to very low. Item 2(prior study design) was the critical item with poor scores, and the non-critical items with poor scores were items 3(explain the selection of the study designs), items 10(report on the sources of funding), and items 16(conflicts of interest stated). In terms of PRISMA 2020, items in eight topics with complete reporting of missing>50%, including search strategy, certainty assessment, results of syntheses, certainty of evidence, registration and protocol, support, competing interests, availability of data, code and other materials. The included SR/MA involved 30 outcome indicators. Evidence quality of mortality, APACHE Ⅱ, and safety, the top three outcome indicators, was evaluated, and all of them were graded as the medium level. The lack of random allocation sequence, allocation concealment mechanism, blinding, and trial sample size was the main reason for the reduction of the evidence level. The available evidence shows that Chinese herbal injections can serve as an effective and safe adjunctive treatment for sepsis, which can reduce mortality, inhibit inflammation, improve coagulation function, and regulate immune function, tissue perfusion, and oxygenation in patients with sepsis. However, the quality of SR/MA was suboptimal, and more high-quality SR/MA is needed to provide evidence to support the efficacy and safety of Chinese herbal injections in the treatment of sepsis.

Association between type of drinking water and upper gastrointestinal cancer incidence in the Linxian General Population.

BACKGROUND: This study aimed to explore the association between drinking water source and risk of upper gastrointestinal (UGI) cancer, including esophageal cancer (EC) and gastric cancer (GC), in the Linxian General Population Nutrition Intervention Trial (NIT) cohort. METHODS: In this study, we used data from the Linxian NIT cohort, which included 29,584 healthy adults aged 40 to 69 years. Subjects were enrolled in April 1986 and followed up until March 2016. Tap water drinking status and demographic characteristics were collected at baseline. Subjects who drank tap water were treated as the exposed group. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated using the Cox proportional hazard model. RESULTS: A total of 5,463 cases of UGI cancer were identified during the 30-year follow-up period. After adjusting for multiple factors, the incidence rate of UGI cancer in participants who drank tap water was significantly lower compared with individuals in the control (HR = 0.91, 95% CI: 0.86-0.97). A similar association was observed between tap water drinking and EC incidence (HR = 0.89, 95% CI: 0.82-0.97). The association between drinking tap water and risk of UGI cancer and EC incidence did not vary across the subgroup by age and gender (All Pinteraction > 0.05). For EC incidence, an interaction effect was observed for riboflavin/niacin supplements and drinking water source (Pinteraction = 0.03). No association was observed between drinking water source and GC incidence. CONCLUSIONS: In this prospective cohort study in Linxian, participants who drank tap water had a lower risk of EC incidence. As a source of drinking water, use of tap water may reduce the risk of EC by avoiding exposure to nitrate/nitrite. Measures should be taken to improve the quality of drinking water in high-incidence areas of EC. TRIAL REGISTRATION: The trial is registered with ClinicalTrials.gov (NCT00342654, 21/06/2006), and the trial name is Nutrition Intervention Trials in Linxian Follow-up Study.

Redox and pH dual sensitive carboxymethyl chitosan functionalized polydopamine nanoparticles loaded with doxorubicin for tumor chemo-photothermal therapy.

The high expression of reduced glutathione (GSH) and low pH in tumor sites have encouraged new ideas for targeted drug release. The tumor microenvironment is a crucial target for studying the anti-tumor efficiency of photothermal therapy because the microenvironment plays a key role in cancer progression, local resistance, immune escaping, and metastasis. Herein, active mesoporous polydopamine nanoparticles loaded with doxorubicin and functionalized with N,N'-bis(acryloyl)cystamine (BAC) and cross-linked carboxymethyl chitosan (CMC) were used to induce simultaneous redox- and pH-sensitive activity to achieve photothermal enhanced synergistic chemotherapy. The inherent disulfide bonds of BAC were able to deplete glutathione, thus increasing the oxidative stress in tumor cells and enhancing the release of doxorubicin. Additionally, the imine bonds between CMC and BAC were stimulated and decomposed in the acidic tumor microenvironment, improving the efficiency of light conversion through exposure to polydopamine. Moreover, in vitro and in vivo investigations demonstrated that this nanocomposite exhibited improved selective doxorubicin release in conditions mimicking the tumor microenvironment and low toxicity towards non-cancerous tissues, suggesting there is high potential for the clinical translation of this synergistic chemo-photothermal therapeutic agent.

Overview of systematic reviews of Chinese herbal injections for sepsis / 中国中药杂志

In this study, an overview of systematic reviews/Meta-analysis(SR/MA) of Chinese herbal injections for sepsis was performed to provide references for clinical practice and promote the quality improvement of clinical evidence. Eight Chinese and English databases such as CNKI, Medline, and EMbase were electronically searched for SR/MA of Chinese herbal injections for sepsis from database inception to June 2022. AMSTAR 2, PRISMA 2020, and GRADE system, combined with Recommendations for Clinical Evidence Grading on Traditional Chinese Medicine Based on Evidence Body, were applied to evaluate the methodological quality, reporting quality, and evidence quality of the included articles. Twenty-seven articles of SR/MA were included, containing four Chinese herbal injections(Xuebijing Injection, Shenfu Injection, Shenmai Injection, and Shengmai Injection). AMSTAR 2 checklist showed that the methodological quality of the SR/MA ranged from moderate to very low. Item 2(prior study design) was the critical item with poor scores, and the non-critical items with poor scores were items 3(explain the selection of the study designs), items 10(report on the sources of funding), and items 16(conflicts of interest stated). In terms of PRISMA 2020, items in eight topics with complete reporting of missing>50%, including search strategy, certainty assessment, results of syntheses, certainty of evidence, registration and protocol, support, competing interests, availability of data, code and other materials. The included SR/MA involved 30 outcome indicators. Evidence quality of mortality, APACHE Ⅱ, and safety, the top three outcome indicators, was evaluated, and all of them were graded as the medium level. The lack of random allocation sequence, allocation concealment mechanism, blinding, and trial sample size was the main reason for the reduction of the evidence level. The available evidence shows that Chinese herbal injections can serve as an effective and safe adjunctive treatment for sepsis, which can reduce mortality, inhibit inflammation, improve coagulation function, and regulate immune function, tissue perfusion, and oxygenation in patients with sepsis. However, the quality of SR/MA was suboptimal, and more high-quality SR/MA is needed to provide evidence to support the efficacy and safety of Chinese herbal injections in the treatment of sepsis.

[Effects of electroacupuncture on the expression of ß-amyloid and autophagy-related proteins in hippocampal cells of mice with Alzheimer's disease].

OBJECTIVE: To investigate the effect of electroacupuncture (EA) on the expression of ß-amyloid (Aß) and autophagy-related proteins in hippocampal cells of Alzheimer's disease (AD) model mice, so as to explore its underlying mechanisms. METHODS: Eighteen male APP/PS1 transgenic mice (6 months old) were randomly divided into model and EA groups, with 9 mice in each group. Nine male C57BL/6 wild-type mice of the same age were chosen as the normal group. Mice in the EA group were treated with acupuncture on "Baihui" (GV20) and EA (1 Hz/50 Hz, 1 mA) on bilateral "Yongquan" (KI1), once every other day, 20 min each time for a total of 21 times. After the interventions, the spatial learning and memory ability were observed by Morris water maze test. The autophagy-related pathological changes in hippocampus were observed by transmission electron microscopy. The expressions of microtublue associated protein 1 light chain 3 (LC3) and Aß in hippocampus were observed by immunofluorescence and the expression levels of LC3 and p62 proteins were detected by Western blot. RESULTS: Compared with the normal group, the escape latency was prolonged (P<0.01), the residence time in the original quadrant platform was shor-tened (P<0.05), the positive expressions of LC3 and Aß, the expression levels of LC3Ⅱ and p62 proteins, and the ratio of LC3Ⅱ/LC3Ⅰ proteins in hippocampus were increased (P<0.01, P<0.05) in the model group. Compared with the model group, the escape latency was shortened (P<0.05), the residence time in the original quadrant platform was prolonged (P<0.05), the positive expressions of LC3 and Aß, the expression levels of LC3Ⅱ and p62 proteins, and the ratio of LC3Ⅱ/LC3Ⅰ proteins in hippocampus were decreased (P<0.05) in the EA group. The transmission electron microscopy showed that the structure of neurons was normal in the normal group, a large number of autolysosomes and autophagosomes existed in hip-pocampal nerve cells in the model group, and only a small number of autophagosomes were observed in the EA group. CONCLUSION: EA can reduce the expression levels of autophagy-related proteins LC3 and p62 in APP/PS1 transgenic mice, improve the hip-pocampal autophagy state, reduce intracellular Aß aggregation, and thus improve the learning and memory ability.

Five Rutaceae family ethanol extracts alleviate H2O2 and LPS-induced inflammation via NF-κB and JAK-STAT3 pathway in HaCaT cells.

This study was designed to investigate the effects of five Rutaceae family ethanol extracts (FRFEE): Citrus medica Linn (CML), Citrus aurantium L. Cv. Daidai (CAD), Citrus medica Linn. var. sarcodactylis (Noot.) Swingle (CMS),Citrus sinensis L. Osbeck (CSO) and Zanthoxylum bungeanum Maxim (ZBM) on retarding the progression of H2O2 and LPS-induced HaCaT cells. Cell inflammatory injury model was established by H2O2 and LPS. The alleviative effects of FRFEE were evaluated by detecting the activity of superoxide dismutase (SOD), glutathione (GSH) and the generation of reactive oxygen species (ROS). The inflammatory signaling pathways of NF-κB and JAK-STAT3 were detected by Western blotting, the mRNA expression levels of inflammatory factors and skin barrier factors were detected by RT-PCR. 50% ethanol extracts of five medicinal and food homologous herbs of Rutaceae family showed different levels of anti-oxidant and anti-inflammatory activities. The FRFEE effectively improved SOD and GSH content and decreased ROS levels. Meanwhile, FRFEE strongly suppressed two inflammatory signaling pathways NF-κB and JAK-STAT3. The RT-PCR examination of inflammatory factors and skin barrier factor revealed significant anti-inflammatory effects of FRFEE. It was worth noting that among the five extracts, Zanthoxylum bungeanum Maxim extract had the best anti-inflammatory and anti-oxidation effects. In addition, it could strongly inhibit the expression of psoriasis factor CCL20. In summary, these results suggested that Zanthoxylum bungeanum Maxim extract could be used as an anti-psoriatic agent in the treatment of psoriasis among FRFEE.

Multiple anti-inflammatory mechanisms of Zedoary Turmeric Oil Injection against lipopolysaccharides-induced acute lung injury in rats elucidated by network pharmacology combined with transcriptomics.

BACKGROUND: Prospects for the drug treatment of acute lung injury (ALI) is unpromising. Managing inflammation can prevent ALI from progressing and minimize further deterioration. Zedoary turmeric oil injection (ZTOI), a patented traditional Chinese medicine (TCM) that has been used against ALI, has shown significant anti-inflammatory effects. However, the mechanisms underlying these effects remain unclear. PURPOSE: Elucidate the anti-inflammatory mechanism by which ZTOI acts against ALI in rats using an ingredients-targets-pathways (I-T-P) interaction network. STUDY DESIGN AND METHODS: The key ingredients of ZTOI were characterized using UPLC-MS/MS combined with literature mining. The target profiles of each ingredient were established using drug-target databases. The anti-inflammatory activity of ZTOI against lipopolysaccharides (LPS)-induced rat ALI was validated using histopathology and inflammatory factor assessments. The therapeutic targets of ZTOI were screened by integrating transcriptomic results of lung tissues with protein-protein interaction (PPI) expansion. Using KEGG pathway enrichment, an I-T-P network was established to determine the essential interactions among ingredients, targets, and pathways of ZTOI against lung inflammation in ALI. Molecular docking and immunofluorescence staining were utilized to confirm the accuracy of the I-T-P network. RESULTS: A total of 11 sesquiterpenes, whose target profiles may characterize the potential function of ZTOI, were identified as key ingredients. In the ALI rat model, ZTOI can alleviate lung inflammation by decreasing the levels of C-reactive protein, interleukin-6, interleukin-1ß, and tumor necrosis factor α both in serum and lung tissues. Based on our biological samples, transcriptomics, PPI network expansion, and KEGG pathway enrichment, 11 ingredients, 174 targets, and 8 signaling pathways were linked in the I-T-P networks. From these results, ZTOI could be inferred to exert multiple anti-inflammatory effects against ALI through Toll-like receptor, NF-kappa B, RIG-I-like receptor, TNF, NOD-like receptor, IL-17, MAPK, and the Toll and Imd signaling pathways. In addition, two significantly regulated targets in the transcriptome, Usp18 and Map3k7, could be the essential anti-inflammatory targets of ZTOI. CONCLUSION: By integrating network pharmacology with ingredient identification and transcriptomics, we show the multiple anti-inflammatory mechanisms by which ZTOI acts against ALI on an I-T-P level. This work also provides a methodological reference for related research into TCM.

The anti-inflammatory effect of Pien Tze Huang in non-alcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease that may progress to nonalcoholic steatohepatitis (NASH), hepatic tissue fibrosis, liver cirrhosis, and hepatocellular carcinoma. In this study, we investigated the effects of Pien Tze Huang (PTH), a well-known traditional Chinese herbal formula with liver protective effect, in methionine-choline deficient diet (MCD)- and high-fat diet (HFD)-induced NASH mouse models. Our results showed that PTH could exert hepatoprotective effects by improving liver weight and steatosis and reducing the fibrosis and serum levels of alanine transaminase (ALT) and aspartate transaminase (AST) in both animal models. The effects of PTH was accompanied with the reduction of infiltrated macrophages, the inhibition of the expression of cytokines, and the induction of adiponectin expression. Mechanistically, we found that PTH could inhibit the activation of proinflammatory transcription factor nuclear factor-κB (NF-κB) by preventing the degradation of inhibitor of κBα (IκBα). These results demonstrate that PTH can improve NAFLD largely due to its suppression of the NF-κB inflammatory pathway.

Targeting NAD+: is it a common strategy to delay heart aging?

Heart aging is the main susceptible factor to coronary heart disease and significantly increases the risk of heart failure, especially when the aging heart is suffering from ischemia-reperfusion injury. Numerous studies with NAD+ supplementations have suggested its use in anti-aging treatment. However, systematic reviews regarding the overall role of NAD+ in cardiac aging are scarce. The relationship between NAD+ signaling and heart aging has yet to be clarified. This review comprehensively summarizes the current studies on the role of NAD+ signaling in delaying heart aging from the following aspects: the influence of NAD+ supplementations on the aging heart; the relationship and cross-talks between NAD+ signaling and other cardiac aging-related signaling pathways; Importantly, the therapeutic potential of targeting NAD+ in delaying heart aging will be discussed. In brief, NAD+ plays a vital role in delaying heart aging. However, the abnormalities such as altered glucose and lipid metabolism, oxidative stress, and calcium overload could also interfere with NAD+ function in the heart. Therefore, the specific physiopathology of the aging heart should be considered before applying NAD+ supplementations. We believe that this article will help augment our understanding of heart aging mechanisms. In the meantime, it provides invaluable insights into possible therapeutic strategies for preventing age-related heart diseases in clinical settings.

[Effects and evaluation of different processing and drying methods on components in Paeoniae Radix Alba].

The present study evaluates different processing and drying methods and investigates their effects on the chemical components in Paeoniae Radix Alba via content determination. The fresh medicinal materials of Paeoniae Radix Alba collected from Bozhou of Anhui province were processed(boiled and peeled) and dried(hot air-dried, infrared-dried, and microwave-dried) at different temperatures(40, 50, 60 and 70 ℃), and the 11 components(monoterpene glycosides, polyphenols, tannin, and benzoic acid) in Paeoniae Radix Alba were determined by ultra-performance liquid chromatography coupled to triple quadrupole with electrospray tandem mass spectrometry(UPLC-TQ-MS). Then the compounds in processed and dried samples were analyzed by partial least squares discriminant analysis(PLS-DA) and orthogonal partial least squares discriminant analysis(OPLS-DA), and the contribution rates of differential components were evaluated by variable important in projection(VIP). The results indicated that the samples obtained by different processing and drying methods could be distinguished. Albiflorin, gallic acid, 1,2,3,4,6-pentakis-O-galloyl-ß-D-glucose, and benzoic acid were the common differential components in boiled Paeoniae Radix Alba. Benzoic acid was the common differential component in peeled Paeoniae Radix Alba. Gallic acid was the common differential component in Paeoniae Radix Alba dried by different methods. The samples could not be distinguished after drying at different temperatures due to the lack of common differential components. This study is expected to provide a reference for the selection of processing and drying methods and the optimization of processing parameters.

Ailanthus Altissima-derived Ailanthone enhances Gastric Cancer Cell Apoptosis by Inducing the Repression of Base Excision Repair by Downregulating p23 Expression.

Chemotherapy plays an irreplaceable role in the treatment of GC, but currently available chemotherapeutic drugs are not ideal. The application of medicinal plants is an important direction for new drug discovery. Through drug screening of GC organoids, we determined that ailanthone has an anticancer effect on GC cells in vitro and in vivo. We also found that AIL can induce DNA damage and apoptosis in GC cells. Further transcriptome sequencing of PDX tissue indicated that AIL inhibited the expression of XRCC1, which plays an important role in DNA damage repair, and the results were also confirmed by western blotting. In addition, we found that AIL inhibited the expression of P23 and that inhibition of P23 decreased the expression of XRCC1, indicating that AIL can regulate XRCC1 via P23. The results of coimmunoprecipitation showed that AIL can inhibit the binding of P23 and XRCC1 to HSP90. These findings indicate that AIL can induce DNA damage and apoptosis in GC cells. Meanwhile, AIL can decrease XRCC1 activity by downregulating P23 expression to inhibit DNA damage repair. The present study sheds light on the potential application of new drugs isolated from natural medicinal plants for GC therapy.

Malayoside, a cardenolide glycoside extracted from Antiaris toxicaria Lesch, induces apoptosis in human non-small lung cancer cells via MAPK-Nur77 signaling pathway.

Lung cancer is the leading cause of cancer deaths in the world. Non-small cell lung cancer (NSCLC), with poor prognosis and resistance to chemoradiotherapy, is the most common histological type of lung cancer. Therefore, it is necessary to develop new and more effective treatment strategy for NSCLC. Nur77, an orphan member of the nuclear receptor superfamily, induces apoptosis in cancer cells including NSCLC cells, by high expression and translocation to mitochondria. Small molecules trigger expression and mitochondrial localization of Nur77 may be an ideal anti-cancer drug candidate. Here, we report malayoside, a cardiac glycoside in the extract of Antiaris toxicaria Lesch., had different sensitivities to NSCLC cells. Malayoside induced apoptosis in NCI-H460 cells. Meanwhile, malayoside induced Nur77 expression and mitochondrial localization, and its induction of apoptosis was Nur77-dependent. To investigate the molecular mechanism of malayoside inducing Nur77 and apoptosis, we found that malayoside activated MAPK signaling pathway, including both ERK and p38 phosphorylation. The suppression of MAPK signaling activation inhibited the expression of Nur77 and apoptosis induced by malayoside. Our studies in nude mice showed that malayside potently inhibited the growth of tumor cells in vivo. Furthermore, the anti-cancer effect of malayosidwas in vivo was also related to the elevated expression of Nur77, p-ERK, and p-p38 proteins. Our results suggest that malayoside possesses an anti-NSCLC activity in vitro and in vivo mainly via activation of MAPK-Nur77 signaling pathway, indicating that malayoside is a promising chemotherapeutic candidate for NSCLC.

Haemostatic indexes for predicting intestinal necrosis in children with intussusception.

BACKGROUND: To determine risk factors for intestinal necrosis in intussusception cases among children with failed non-surgical reduction for intussusception. METHODS: Totally, 540 hospitalized individuals with unsuccessful air-enema reduction in our hospital between November 2010 and November 2020 were assessed in this retrospective study. The 540 intussusception cases were divided into the intestinal necrosis and non-intestinal necrosis groups. Haemostatic parameters, demographic and clinical features were assessed. Predictors of intestinal necrosis were examined by univariable and multivariable logistic regression analyses. RESULTS: Of the 540 patients included, 113 showed intestinal necrosis. This intestinal necrosis group had a longer duration of symptom or length of illness, younger ages, higher platelet counts, fibrinogen amounts and d-dimer levels (all P = 0.000) compared with the non-intestinal necrosis group. Multivariable analysis revealed that duration of symptom (odds ratio (OR) 1.12; 95% confidence interval (CI) 1.16-1.23, P = 0.000), fibrinogen (OR 1.26; 95% CI 1.10-1.31, P = 0.010) and d-dimer (OR 2.07; 95% CI 1.91-2.28, P = 0.000) independently predicted intestinal necrosis in individuals undergoing surgical reduction for intussusception. Receiver operating characteristic curve analysis showed that d-dimer amounts had the largest area under the curve for predicting intestinal necrosis. CONCLUSION: On admission, long duration of symptom, high fibrinogen and d-dimer levels are critical risk factors for intestinal necrosis development in children with unsuccessful non-surgical reduction. d-Dimer levels have the best predictive value for intestinal necrosis.

Neuroprotective Effects of Early Hypothermia Induced by Phenothiazines and DHC in Ischemic Stroke.

METHODS: Adult male Sprague Dawley rats were studied in 4 groups: (1) sham; (2) stroke; (3) stroke treated with pharmacological hypothermia before reperfusion (interischemia hypothermia); and (4) stroke treated with pharmacological hypothermia after reperfusion is initiated (inter-reperfusion hypothermia). The combination of chlorpromazine and promethazine with dihydrocapsaicin (DHC) was used to induce hypothermia. To compare the neuroprotective effects of drug-induced hypothermia between the interischemia and inter-reperfusion groups, brain damage was evaluated using infarct volume and neurological deficits at 24 h reperfusion. In addition, mRNA expressions of NADPH oxidase (NOX) subunits (gp91phox, p67phox, p47phox, and p22phox) and glucose transporter subtypes (GLUT1 and GLUT3) were determined by real-time PCR at 6 and 24 h reperfusion. ROS production was measured by flow cytometry assay at the same time points. RESULTS: In both hypothermia groups, the cerebral infarct volumes and neurological deficits were reduced in the ischemic rats. At 6 and 24 h reperfusion, ROS production and the expressions of NOX subunits and glucose transporter subtypes were also significantly reduced in both hypothermia groups as compared to the ischemic group. While there were no statistically significant differences between the two hypothermia groups at 6 h reperfusion, brain damage was significantly further decreased by interischemia hypothermia at 24 h. CONCLUSION: Both interischemia and inter-reperfusion pharmacological hypothermia treatments play a role in neuroprotection after stroke. Interischemia hypothermia treatment may be better able to induce stronger neuroprotection after ischemic stroke. This study provides a new avenue and reference for stronger neuroprotective hypothermia before vascular recanalization in stroke patients.

Enteral immunonutrition versus enteral nutrition for patients undergoing esophagectomy: a randomized controlled trial.

BACKGROUND: In recent years, immunonutrition has been introduced and proposed to have a positive modulatory effect on inflammatory and immune responses and gut function for surgical patients, especially for patients undergoing gastrointestinal cancer resection. We conducted this parallel-group, randomized and double-blind clinical controlled trial to investigate the efficacy of perioperative enteral immunonutrition (EIN) on clinical and immunological outcomes of patients undergoing esophageal resection. METHODS: A randomized, parallel-group, double-blind, clinical trial was conducted between December 1, 2017 and March 1, 2018. This study enrolled 120 patients with esophageal cancer. And 112 patients were divided into two groups randomly: EIN group and enteral nutrition (EN) group. The EIN contained extra immunonutritional substrates, including a consistent combination of arginine, RNA and the omega-3 fatty acids compared with EN. Immune indicators were measured at preoperative day 7, postoperative day (POD) 1, 3, 7 and post-discharge day (PDD) 30. RESULTS: There were 56 participants randomized to each group. Finally, 53 patients in EIN and 50 patients in EN were analyzed. Immune indicator was the primary outcome in this study. EIN yielded a significantly lower rate of CD8/CD3 (%) at POD 3 compared with EN group (P=0.005). The rate of CD4/CD8 (%) in EIN group was higher than that in EN group at POD3 (P=0.004). The serum levels of IgM at POD 3 and 7 were significantly higher in EN group compared with EIN group (P=0.025 and P=0.009, respectively). The rate of NK (%) and the serum level of IgA were significantly higher in EIN group compared with EN group at PDD 30 (P=0.022 and P=0.041, respectively). No significant differences were found in 2-year progressionfree survival and overall survival. CONCLUSIONS: Immunonutrition is a safe and feasible nutritional treatment, which has a positive modulatory impact on immune responses after esophagectomy. Although no significant difference was found in clinical and survival outcomes between EIN and EN groups, immunonutrition could still have a positive effect on immunological function of patients undergoing esophagectomy.

Effects and evaluation of different processing and drying methods on components in Paeoniae Radix Alba / 中国中药杂志

The present study evaluates different processing and drying methods and investigates their effects on the chemical components in Paeoniae Radix Alba via content determination. The fresh medicinal materials of Paeoniae Radix Alba collected from Bozhou of Anhui province were processed(boiled and peeled) and dried(hot air-dried, infrared-dried, and microwave-dried) at different temperatures(40, 50, 60 and 70 ℃), and the 11 components(monoterpene glycosides, polyphenols, tannin, and benzoic acid) in Paeoniae Radix Alba were determined by ultra-performance liquid chromatography coupled to triple quadrupole with electrospray tandem mass spectrometry(UPLC-TQ-MS). Then the compounds in processed and dried samples were analyzed by partial least squares discriminant analysis(PLS-DA) and orthogonal partial least squares discriminant analysis(OPLS-DA), and the contribution rates of differential components were evaluated by variable important in projection(VIP). The results indicated that the samples obtained by different processing and drying methods could be distinguished. Albiflorin, gallic acid, 1,2,3,4,6-pentakis-O-galloyl-β-D-glucose, and benzoic acid were the common differential components in boiled Paeoniae Radix Alba. Benzoic acid was the common differential component in peeled Paeoniae Radix Alba. Gallic acid was the common differential component in Paeoniae Radix Alba dried by different methods. The samples could not be distinguished after drying at different temperatures due to the lack of common differential components. This study is expected to provide a reference for the selection of processing and drying methods and the optimization of processing parameters.