Genomic dynamics of the Lower Yellow River Valley since the Early Neolithic.

The Yellow River Delta played a vital role in the development of the Neolithic civilization of China. However, the population history of this region from the Neolithic transitions to the present remains poorly understood due to the lack of ancient human genomes. This especially holds for key Neolithic transitions and tumultuous turnovers of dynastic history. Here, we report genome-wide data from 69 individuals dating to 5,410-1,345 years before present (BP) at 0.008 to 2.49× coverages, along with 325 present-day individuals collected from 16 cities across Shandong. During the Middle to Late Dawenkou period, we observed a significant influx of ancestry from Neolithic Yellow River farmers in central China and some southern Chinese ancestry that mixed with local hunter-gatherers in Shandong. The genetic heritage of the Shandong Longshan people was found to be most closely linked to the Dawenkou culture. During the Shang to Zhou Dynasties, there was evidence of genetic admixture of local Longshan populations with migrants from the Central Plain. After the Qin to Han Dynasties, the genetic composition of the region began to resemble that of modern Shandong populations. Our genetic findings suggest that the middle Yellow River Basin farmers played a role in shaping the genetic affinity of neighboring populations in northern China during the Middle to Late Neolithic period. Additionally, our findings indicate that the genetic diversity in the Shandong region during the Zhou Dynasty may be linked with their complex ethnicities.

Significance of concurrent evaluation of HER2 gene amplification and p53 and Ki67 expression in gastric cancer tissues.

OBJECTIVE: The primary objective of this study is to explore the significance of concurrent evaluation of HER2 gene amplification and p53 and Ki67 expression in gastric cancer tissues. METHODS: Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) methodologies were used to detect HER2 gene amplification, as well as the expression levels of HER2, p53, and Ki67 proteins, across a group of 78 gastric cancer cases. RESULTS: The expression rate of the HER2 protein was determined to be 43.6% (34/78), with 17.9% (14/78) categorized as HER2 protein 3 + , 14.1% (11/78) as HER2 protein 2 + , and 11.5% (9/78) as HER2 protein 1 + . Using FISH technology, the HER2 gene amplification rate was identified as 19.2% (15/78), including 3 cases of HER2 gene cluster amplification, 5 cases of large granular amplification, 4 cases of punctate amplification, and 3 cases of high polysomy. The positive rate of p53 in gastric cancer cells was 52.6% (41/78), with 62.8% (49/78) of patients exhibiting a ki67 proliferation index ≤ 30, and 37.2% (29/78) accounting for a ki67 proliferation index > 30. The expression rates of the HER2 gene, p53, and ki67 in gastric cancer tissues were significantly associated with both gastric cancer staging and lymph node metastasis (P < 0.05). CONCLUSION: The HER2 gene amplification rate and gene copy number exhibit a positive correlation with the expression rates of p53 and ki67. Combining these assessments can provide crucial insights into the assessment of metastatic potential, disease progression, and prognosis of gastric tumor cells. This holds paramount importance in steering the formulation of individualized treatment strategies.

Assessing clinical pathological characteristics and gene expression patterns associated with hepatoid adenocarcinoma of the stomach.

OBJECTIVE: The objective of this study is to assess the clinical pathological attributes of Hepatoid Adenocarcinoma of the Stomach (HAS) and to delineate the differential diagnostic considerations about it. METHOD: The investigation involved analyzing 31 HAS cases using histomorphological assessment, immunohistochemical profiling, and relevant gene detection methodologies. RESULTS: Among the 31 HAS cases, 9 (29.0%) were of trabecular hepatoid adenocarcinoma of the stomach, 7 (22.6%) were of glandular hepatoid adenocarcinoma of the stomach, 4 (12.9%) were of nesting hepatoid adenocarcinoma of the stomach, 3 (9.7%) were of clear cell hepatoid adenocarcinoma of the stomach, and 8 (25.8%) were of diverse hepatoid adenocarcinoma of the stomach. Of these 31 cases, 24 were male, accounting for 77.4% of the cases. Serum alpha-fetoprotein (AFP) levels were notably elevated, with radioimmunoassay results reaching 1240 ng/ml; 28 out of 31 cases had AFP levels below 25 µg/l, accounting for 90.3%. Related genes: HER2 protein indicated positive expression on the cell membrane in 35.5% (11/31) of the cases; HER2 gene amplification detected by the FISH technique was 12.9% (4/31). Tumoral stromal lymphocytes exhibited a PD-1 positive expression rate of 58.1% (18/31). In gastric cancer tissues, the PD-L1 positive rate was 45.1% (14/31). CONCLUSION: HAS represents a distinctive subtype of gastric cancer with a propensity for mimicking other forms of tumors, underscoring the significance of discerning its unique histopathological attributes for accurate differential diagnosis and tailored therapeutic interventions.

Histopathological staging and differential diagnosis of marginal zone lymphoma of gastric mucosa-associated lymphoid tissue.

The purpose of this study was to explore the histopathological staging and differential diagnosis of marginal zone lymphoma in gastric mucosa-associated lymphoid tissue (MALT lymphoma). We performed detailed histomorphology and immunohistochemistry investigations as well as genetic testing on endoscopic biopsy and endoscopic mucosal resection specimens from 18 patients with gastric MALT lymphoma. We found that gastric MALT lymphoma typically begins as a small, isolated area outside the lymphoid follicular mantle zone or proliferates in a multifocal, patchy manner, gradually spreads to the interfollicular zone, forming diffuse proliferation, invades the gastric mucosal glands, and infiltrates or proliferates into the center of peripheral reactive lymphoid follicles. Abnormally proliferating lymphocytes invade the surrounding lymphoid follicles, resulting in damage, atrophy, and disappearance of their normal follicles as well as of the gastric mucosa glands, forming diffuse proliferation. Redifferentiation and proliferation lead to the transformation of lymphocytes; that is, MALT transitions into highly invasive lymphoma. Based on our findings in this study, we propose the following five stages in the process of development and progression of gastric MALT lymphoma: the stage of cell proliferation outside the lymphoid follicular mantle zone; the stage of heterogeneous proliferative lymphoepithelial lesion; the stage of reactive lymphoid follicular implantation; the stage of lymphoid follicular clonal proliferation; and the stage of MALT transforming into highly invasive lymphoma. We examined the differential diagnosis of histopathological features at each stage. The clinicopathological staging of gastric MALT lymphoma can help clinicians provide accurate treatment and track malignant cell transformation, thus playing a significant role in controlling its development and progression.

Examining the Significance of Intercultural Communicative Competence Development in Trainees during Pre-service Training.

The aim of this study is to discuss the need for improved intercultural communicative competence (ICC) training for pre-service Chinese as a Second Language (CSL) teachers who travel abroad to teach. Previous studies have shown that pre-service CSL teachers often struggle with intercultural communication, and this study investigates the reasons behind their difficulties and suggests ways to address them. The researchers used the Intercultural Sensitivity Scale (ISS) and the Intercultural Effectiveness Scale (IES) to measure the ICC of 217 pre-service CSL teachers. The study found that while pre-service CSL teachers have strong intercultural communicative emotional ability, their behavioral ability in intercultural communication is weak. In particular, they lacked skills in interactive control, interactive relaxation, identity management, information skills, and behavioral flexibility. The study proposes several strategies to improve ICC training for pre-service CSL teachers. One potential approach is the use of Computer Assisted Language Learning to provide teacher-trainee students with opportunities to practice intercultural communication skills in simulated contexts, receive personalized feedback, and engage with authentic materials and cultural information relevant to their host country. CALL could also facilitate communication between pre-service CSL teachers and former CSL teachers, providing a platform for information exchange and additional psychological support. The study also suggests that pre-service training should distinguish between foreign language learning and intercultural communication skills training. Specifically, it recommends that foreign language proficiency should be improved, while training should focus on educational culture and work culture in the host country, rather than providing a general introduction to the national conditions of the country. Finally, the study proposes that pre-service training should establish contact between pre-service CSL teachers and former CSL teachers as early as possible so that trainees can learn specific relevant information in advance, which can help them get ready, avoid intercultural communication mistakes, and obtain additional psychological support. By incorporating CALL and addressing the areas of weakness identified in the study, pre-service CSL teachers can be better prepared to navigate the challenges of intercultural communication and provide effective and culturally sensitive instruction abroad.

Study on the Characteristics of Early Cytokine Storm Response to Cardiac Surgery.

Cardiac surgery can provoke an acute cytokine storm that may contribute to the development of postoperative multiple organ dysfunction syndrome. We prospectively observed patients undergoing cardiac surgery and divided them into two groups: the severe group and the mild group. Healthy individuals were enrolled acting as the control group for comparison. Plasma samples and clinical data were recorded at the initiation of cardiac-pulmonary bypass (CPB) and 3, 6, 12, 24, and 48 h after initiation of CPB. Cytokine levels were detected using the Luminex® technique. Thirty-nine adults were enrolled in this study (14 in the severe group, 15 in the mild group, and 10 in the control group). Cytokine concentrations were significantly higher in the severe group. Principal component analysis was used to establish a cytokine storm intensity curve, which represented the overall trend of 10 cytokines. The peak concentrations of interleukin (IL)-6, IL-10, and IL-16 were 425.1, 198.5, and 623.0 pg/mL, which were more than 1,200, 1,800, and 240 times the normal level, respectively. The maximum cytokine storm intensity predated the maximum Vasoactive-Inotropic Score (VIS) and Sequential Organ Failure Assessment (SOFA) score in the severe group. Cytokine storm response to cardiac surgery occurred early and was associated with disease severity. Interventions to cytokine storm should be initiated early as guided by cytokine storm biomarkers such as IL-6, IL-10, and IL-16 in severe patients undergoing cardiac surgery. Clinical Trial Registration: ChiCTR1900021351.

Structural and nonstructural proteins of Senecavirus A: Recent research advances, and lessons learned from those of other picornaviruses.

Senecavirus A (SVA) is an emerging virus, causing vesicular disease in swine. SVA is a single-stranded, positive-sense RNA virus, which is the only member of the genus Senecavirus in the family Picornaviridae. SVA genome encodes 12 proteins: L, VP4, VP2, VP3, VP1, 2A, 2B, 2C, 3A, 3B, 3C and 3D. The VP1 to VP4 are structural proteins, and the others are nonstructural proteins. The replication of SVA in host cells is a complex process coordinated by an elaborate interplay between the structural and nonstructural proteins. Structural proteins are primarily involved in the invasion and assembly of virions. Nonstructural proteins modulate viral RNA translation and replication, and also take part in antagonizing the antiviral host response and in disrupting some cellular processes to allow virus replication. Here, we systematically reviewed the molecular functions of SVA structural and nonstructural proteins by reference to literatures of SVA itself and other picornaviruses.

Design of a Fuzzy Algorithm-Based Evaluation System for the Effectiveness of International Online Chinese Listening and Speaking Teaching.

With the increasing popularity of online foreign language teaching and learning practice, learners and teachers have developed a high demand for evaluation of teaching effectiveness. When we focus discussion on international Chinese teaching, which has been developed for a relatively short time and not experienced enough, online teaching effectiveness evaluation has become an important obstacle to the development of teaching. This paper introduces a hybrid technique based on fuzzy evaluation method, for determining and suggesting possible types of errors in international Chinese online listening and speaking instruction and giving suggestions for improvement. The system can help learners to identify and determine the types of errors in Chinese listening and speaking learning in a timely manner and make a more objective and comprehensive evaluation of learning performance; at the same time, it helps teachers to trace the effectiveness of teaching design and implementation in a targeted manner and make corresponding scientific decisions. This hybrid technology combines existing language teaching evaluation models, takes advantage of data from online education, and creates corresponding criteria through machine learning fuzzy algorithms and large data sample training, combined with the theory of effective teaching evaluation, which is beneficial for all participants of online Chinese listening and speaking teaching to improve their learning effectiveness.

[Sagittaria sagittifolia polysaccharides regulates Nrf2/HO-1 to relieve liver injury caused by multiple heavy metals in vivo and in vitro].

This study explored whether Sagittaria sagittifolia polysaccharides(SSP) activates the nuclear factor erythroid-2-related factor2(Nrf2)/heme oxygenase-1(HO-1) signaling pathway to protect against liver damage jointly induced by multiple heavy metals. First, based on the proportion of dietary intake of six heavy metals in rice available in Beijing market, a heavy metal mixture was prepared for inducing mouse liver injury and HepG2 cell injury. Forty male Kunming mice were divided into five groups: control group, model group, glutathione positive control group, and low-and high-dose SSP groups, with eight mice in each group. After 30 days of intragastric administration, the liver injury in mice was observed by HE staining. In the in vitro experiment, MTT assay was conducted to detect the effects of SSP at 0.25, 0.5, 1, and 2 mg·mL~(-1) on HepG2 cell survival at different time points. The content of alanine transaminase(ALT) and aspartate aminotransferase(AST) in the 48-h cell culture fluid was measured using micro-plate cultivation method, followed by the detection of the change in reactive oxygen species(ROS) content by flow cytometry. The mRNA expression levels of Nrf2 and HO-1 in cells were determined by RT-PCR, and their protein expression by Western blot. HE staining results showed that compared with the model group, the SSP administration groups exhibited significantly alleviated inflammatory cell infiltration and fatty infiltration in the liver, with better outcomes observed in the high-dose SSP group. In the in vitro MTT assay, compared with the model group, SSP at four concentrations all significantly increased the cell survival rate, decreased the ALT, AST, and ROS content(P<0.05), and down-regulated Nrf2 and HO-1 mRNA and protein expression(P<0.05). SSP significantly improves inflammatory infiltration in the liver tissue of mice exposed to a variety of heavy metals and corrects the liver fat degeneration, which may be related to its regulation of the Nrf2/HO-1 signaling pathway, reduction of ROS, and alleviation of oxidative damage.

Prediction of the Maturity of Greenhouse Grapes Based on Imaging Technology.

To predict grape maturity in solar greenhouses, a plant phenotype-monitoring platform (Phenofix, France) was used to obtain RGB images of grapes from expansion to maturity. Horizontal and longitudinal diameters, compactness, soluble solid content (SSC), titratable acid content, and the SSC/acid of grapes were measured and evaluated. The color values (R, G, B, H, S, and I) of the grape skin were determined and subjected to a back-propagation neural network algorithm (BPNN) to predict grape maturity. The results showed that the physical and chemical properties (PCP) of the three varieties of grapes changed significantly during the berry expansion stage and the color-changing maturity stage. According to the normalized rate of change of the PCP indicators, the ripening process of the three varieties of grapes could be divided into two stages: an immature stage (maturity coefficient Mc < 0.7) and a mature stage (after which color changes occurred) (0.7 ≤ Mc < 1). When predicting grape maturity based on the R, G, B, H, I, and S color values, the R, G, and I as well as G, H, and I performed well for Drunk Incense, Muscat Hamburg, and Xiang Yue grape maturity prediction. The GPI ranked in the top three (up to 0.87) when the above indicators were used in combination with BPNN to predict the grape Mc by single-factor and combined-factor analysis. The results showed that the prediction accuracy (RG and HI) of the two-factor combination was better for Drunk Incense, Muscat Hamburg, and Xiang Yue grapes (with recognition accuracies of 79.3%, 78.2%, and 79.4%, respectively), and all of the predictive values were higher than those of the single-factor predictions. Using a confusion matrix to compare the accuracy of the Mc's predictive ability under the two-factor combination method, the prediction accuracies were in the following order: Xiang Yue (88%) > Muscat Hamburg (81.3%) > Drunk Incense (76%). The results of this study provide an effective way to predict the ripeness of grapes in the greenhouse.

Sagittaria sagittifolia polysaccharide protects against six-heavy-metal-induced hepatic injury associated with the activation of Nrf2 pathway to regulate oxidative stress and apoptosis.

The hepatic protective role of Sagittaria sagittifolia polysaccharide (SSP) and its possible mechanism were discussed in mice and L02 hepatocytes injured by heavy metals mixture of Cd + Cr (VI) + Pb + Mn + Zn + Cu. After 30-day intervention, blood and liver samples were collected for the relevant assessments. Methyl thiazolyl tetrazolium (MTT) assay showed 24 h was the best protecting point and the SSP protection at 1 mg/mL was strongest in L02 hepatocytes. SSP can alleviated hepatic injury, as evidenced by significantly decreased the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and the malondialdehyde (MDA) content, also increased the superoxide dismutase (SOD) activity and glutathione (GSH), total sulphydryl (T-SH) contents. SSP effectively reduced pathological damage of mice and accumulation of heavy metals in liver, as well as decreased the level of reactive oxygen species (ROS) in L02 hepatocytes. After SSP treatment, the protein expressions or gene transcription of nuclear factor erythroid 2-related factor 2 (Nrf2), NAD(P)H dehydrogenase, quinone 1 (NQO1) and heme oxygenase1 (HO-1) decreased in L02. The protein expression of Nrf2 and NQO1 were increased while HO-1 was decreased in liver. Besides, SSP can attenuates apoptosis through reducing the protein expression of Bcl-2-associated X protein (Bax) and caspase-3, and increasing B-cell lymphoma gene 2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xl). SSP protects against six-heavy-metal-induced hepatic injury in mice and L02 hepatocytes. Supported by Nrf2 gene silencing, the mechanisms may correlate with activating Nrf2 pathway to mitigate oxidative stress and apoptosis.

Efficacy and safety of ciprofol for agitation and delirium in the ICU: A multicenter, single-blind, 3-arm parallel randomized controlled trial study protocol.

Background: Agitation is very common in the intensive care unit (ICU). The causes include pain, delirium, underlying disease, withdrawal syndrome, and some drug treatments. The practical goal of ICU treatment is to find an appropriate sedation regimen to reduce pain, restlessness, and delirium. Previous trials have examined the use of dexmedetomidine, but no trials have evaluated the efficacy and safety of ciprofol, a new sedative drug. Methods: This study was a multicenter, single-blind, 3-arm parallel randomized controlled trial. ICU patients aged ≥ 18 years with agitation and delirium who met the eligibility criteria were included. The main outcome was the proportion of patients who needed additional study medication or midazolam due to agitation within 4 h after the first intravenous injection of the study medication. The secondary outcomes included the pass rate as indicated by a Richmond Agitation-Sedation Scale (RASS) score < +1, the effectiveness rate of improving delirium symptoms, the number of recurrences of agitation within 24 h, the incidence of rescue treatment, the dose and cost of analgesic and sedative drugs, the length and cost of ICU stay, and the 30-day survival period. The safety evaluation included the incidence of adverse events (hypotension, bradycardia, hypoxia, etc.) and the rate of endotracheal intubation. The subjects were randomly assigned to receive ciprofol, dexmedetomidine, or normal saline at a ratio of 1:1:1. The rates of additional drug administration within 4 h after the first injection of the study drug in the three groups were 40, 50, and 90%, respectively. A total sample size of 81 subjects was required to reach 90% power and an α of 0.05. Considering a 20% loss rate, 102 patients were enrolled and randomly assigned to the three groups in equal proportions. Ethics and communication: This trial was approved by the Ethics Committee of Dalian Municipal Central Hospital. The communication plan includes presentations at scientific conferences, scientific publications, and presentations to the public through non-professional media. Clinical trial registration: www.ClinicalTrials.gov, identifier ChiCTR220006 2799.

Circular RNA hsa_circ_0001658 Inhibits Intervertebral Disc Degeneration Development by Regulating hsa-miR-181c-5p/FAS.

METHODS: We obtained microarray data (GSE116726, GSE67566) from Gene Expression Omnibus database, and differential expression level of ncRNA in nucleus pulposus (NP) tissues of IDD patients was analyzed. The potential circRNA-miRNA-mRNA regulatory network was analyzed by starBase. The effect of the interaction between hsa_circ_0001658, hsa-miR-181c-5p, and FAS on the proliferation and apoptosis of human neural progenitor cells (hNPCs) was studied. RESULTS: hsa_circ_0001658 was significantly upregulated (logFC > 2.0 and adj.P.Val < 0.01) in the NP tissues of IDD patients, and hsa-miR-181c-5p expression was downregulated (logFC < -2.0 and adj.P.Val < 0.01). Silencing of hsa-miR-181c-5p or overexpression of hsa_circ_0001658 inhibited the proliferation of hNPCs and promoted their apoptosis. hsa_circ_0001658 acted as a sponge of hsa-miR-181c-5p. hsa-miR-181c-5p downregulated the expression of Fas cell surface death receptor (FAS), promoted the proliferation, and inhibited the apoptosis of hNPCs. hsa_circ_0001658 functioned in hNPCs through targeting hsa-miR-181c-5p/FAS. CONCLUSION: Circular RNA hsa_circ_0001658 inhibits IDD development by regulating hsa-miR-181c-5p/FAS. It is expected to be a potential target for the therapy of IDD.

Effect of electroacupuncture on glial fibrillary acidic protein and nerve growth factor in the hippocampus of rats with hyperlipidemia and middle cerebral artery thrombus.

Electroacupuncture (EA) has been shown to reduce blood lipid level and improve cerebral ischemia in rats with hyperlipemia complicated by cerebral ischemia. However, there are few studies on the results and mechanism of the effect of EA in reducing blood lipid level or promoting neural repair after stroke in hyperlipidemic subjects. In this study, EA was applied to a rat model of hyperlipidemia and middle cerebral artery thrombosis and the condition of neurons and astrocytes after hippocampal injury was assessed. Except for the normal group, rats in other groups were fed a high-fat diet throughout the whole experiment. Hyperlipidemia models were established in rats fed a high-fat diet for 6 weeks. Middle cerebral artery thrombus models were induced by pasting 50% FeCl3 filter paper on the left middle cerebral artery for 20 minutes on day 50 as the model group. EA1 group rats received EA at bilateral ST40 (Fenglong) for 7 days before the thrombosis. Rats in the EA1 and EA2 groups received EA at GV20 (Baihui) and bilateral ST40 for 14 days after model establishment. Neuronal health was assessed by hematoxylin-eosin staining in the brain. Hyperlipidemia was assessed by biochemical methods that measured total cholesterol, triglyceride, low-density lipoprotein and high-density lipoprotein in blood sera. Behavioral analysis was used to confirm the establishment of the model. Immunohistochemical methods were used to detect the expression of glial fibrillary acidic protein and nerve growth factor in the hippocampal CA1 region. The results demonstrated that, compared with the model group, blood lipid levels significantly decreased, glial fibrillary acidic protein immunoreactivity was significantly weakened and nerve growth factor immunoreactivity was significantly enhanced in the EA1 and EA2 groups. The repair effect was superior in the EA1 group than in the EA2 group. These findings confirm that EA can reduce blood lipid, inhibit glial fibrillary acidic protein expression and promote nerve growth factor expression in the hippocampal CA1 region after hyperlipidemia and middle cerebral artery thrombosis. All experimental procedures and protocols were approved by the Animal Use and Management Committee of Beijing University of Chinese Medicine, China (approval No. BUCM-3-2018022802-1002) on April 12, 2018.

Allium tuberosum alleviates pulmonary inflammation by inhibiting activation of innate lymphoid cells and modulating intestinal microbiota in asthmatic mice.

OBJECTIVE: This study tests whether long-term intake of Allium tuberosum (AT) can alleviate pulmonary inflammation in ovalbumin (OVA)-induced asthmatic mice and evaluates its effect on the intestinal microbiota and innate lymphoid cells (ILCs). METHODS: BALB/c mice were divided into three groups: phosphate buffer saline, OVA and OVA + AT. The asthmatic murine model was established by sensitization and challenge of OVA in the OVA and OVA + AT groups. AT was given to the OVA + AT group by oral gavage from day 0 to day 27. On day 28, mice were sacrificed. Histopathological evaluation of lung tissue was performed using hematoxylin and eosin, and periodic acid-Schiff staining. The levels of IgE in serum, interleukin-5 (IL-5) and IL-13 from bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay. The ILCs from the lung and gut were detected by flow cytometry. 16S ribosomal DNA sequencing was used to analyze the differences in colon microbiota among treatment groups. RESULTS: We found that long-term intake of AT decreased the number of inflammatory cells from BALF, reduced the levels of IL-5 and IL-13 in BALF, and IgE level in serum, and rescued pulmonary histopathology with less mucus secretion in asthmatic mice. 16S ribosomal DNA sequencing results showed that AT strongly affected the colonic bacteria community structure in asthmatic mice, although it had no significant effect on the abundance and diversity of the microbiota. Ruminococcaceae and Desulfovibrionaceae were identified as two biomarkers of the treatment effect of AT. Moreover, AT decreased the numbers of ILCs in both the lung and gut of asthmatic mice. CONCLUSION: The results indicate that AT inhibits pulmonary inflammation, possibly by impeding the activation of ILCs and adjusting the homeostasis of gut microbiota in asthmatic mice.

Consumption of Lamb Meat or Basa Fish Shapes the Gut Microbiota and Aggravates Pulmonary Inflammation in Asthmatic Mice.

OBJECTIVE: In China, lamb and fish are well-known triggers for an asthma attack. Our investigation aims at assessing whether the long-term intake of lamb meat or Basa fish would aggravate pulmonary inflammation as well as exploring changes in the intestinal microbiota and immune cells in asthmatic mice. MATERIALS AND METHODS: The murine asthmatic model was established by intraperitoneal injection of ovalbumin (OVA) plus aluminum on day 0 and 14 and nebulization of OVA from day 21 to 27. Lamb meat or fish was administered to asthmatic mice by oral gavage from day 0 to 27. RESULTS: Our results showed that long-term consumption of lamb meat or Basa fish in asthmatic mice increased the number of inflammatory cells in bronchoalveolar lavage fluid (BALF), enhanced levels of IL-5, IL-13 in BALF and total IgE in serum, aggravated pulmonary inflammatory cell infiltration and mucus secretion. Long-term oral lamb enhanced the proportion of type 2 innate lymphoid cells (ILC2) from small intestine while it inhibited that of Treg from lung in asthmatic mice. Oral fish showed no remarkable effect on that of ILC2 from lung and small intestine but inhibited that of intestinal Treg in asthmatic mice. What's more, the chao-1 and observed species richness as well as PD whole tree diversity increased in asthmatic mice while these increments were inhibited after lamb treatment. PCA analysis indicated that there were significant differences in the bacterial community composition after lamb or fish treatment in asthmatic mice. Both lamb and fish treatment enhanced the abundance of colonic Alistipes in asthmatic mice. CONCLUSION: Collectively, long-term intake of lamb or fish shapes colonic bacterial communities and aggravates pulmonary inflammation in asthmatic mice, which provides reasonable food guidance for asthmatic patients.

Detection of Early Cytokine Storm in Patients with Septic Shock After Abdominal Surgery.

Objectives: To explore the characteristics of cytokine storm in patients with septic shock after abdominal surgery, examine its relationship with clinical data, and determine intervention timings. Materials and Methods: We prospectively observed a cohort of patients with abdominal infection admitted to the surgical intensive care unit (ICU) after surgery (shock group). A control group of healthy individuals was used for comparison. Plasma samples and clinical data recorded at 0, 12, 24, 48, and 72 h after surgery were collected. Cytokines (tumor necrosis factor-α, interleukin [IL]-6, IL-8, IL-10, monocyte chemotactic protein [MCP]-1, IL-1 ß, interferon-γ, IL-12p70, MCP-1α, IL-4, IL-2, and IL-13) were detected using the Luminex® technique. Results: Concentrations of most cytokines were significantly higher in the shock group. When a cytokine storm intensity curve was considered with the vasopressor dependency index and a Sequential Organ Failure Assessment (SOFA) score, time point of maximum cytokine storm intensity was earlier than that of the maximum vasopressor dependency index and SOFA score in the shock group. Conclusions: Cytokine storm occurred in patients with septic shock shortly after the abdominal surgery and may be a main mechanism leading to septic shock. Cytokine storm interventions should ideally be initiated within 24 h after surgery and be guided by cytokine storm biomarkers.

A comparative study of microbial community and functions of type 2 diabetes mellitus patients with obesity and healthy people.

The gut microbiota is crucial in the pathogenesis of type 2 diabetes mellitus (T2DM). However, the metabolism of T2DM patients is not well-understood. We aimed to identify the differences on composition and function of gut microbiota between T2DM patients with obesity and healthy people. In this study, 6 T2DM patients with obesity and 6 healthy volunteers were recruited, and metagenomic approach and bioinformatics analysis methods were used to understand the composition of the gut microbiota and the metabolic network. We found a decrease in the abundance of Firmicutes, Oribacterium, and Paenibacillus; this may be attributed to a possible mechanism and biological basis of T2DM; moreover, we identified three critical bacterial taxa, Bacteroides plebeius, Phascolarctobacterium sp. CAG207, and the order Acidaminococcales that can potentially be used for T2DM treatment. We also revealed the composition of the microbiota through functional annotation based on multiple databases and found that carbohydrate metabolism contributed greatly to the pathogenesis of T2DM. This study helps in elucidating the different metabolic roles of microbes in T2DM patients with obesity.

[Effect of acupuncture at different layers of local "Neiguan" (PC6) tissue on arrhythmia and expression of myocardial Cx43 in rabbits].

OBJECTIVE: To compare the therapeutic effect of shallow and deep needling at "Neiguan"(PC6) in the treatment of arrhythmia in rabbits. METHODS: Male New Zealand rabbits were randomly divided into saline (n＝15), model (n＝12), shallow needling (n＝13) and deep needling (n＝12) groups. The arrhythmia model was established by ear intravenous injection of Barium chloride (0.4%, 1 mL/kg). Acupuncture needle was inserted into the superficial fascia (about 3 mm beneath the skin) or deep layer (5 to 8 mm, near the median nerve) of local PC6 tissue (fore limb), manipulated for a while and then retained for 10 min. Histopathological changes of myocardium was observed after H．E. stain, and the immunoactivity of connexin 43 (Cx43) detected by immunohistochemistry(IHC). RESULTS: Various degrees of arrhythmia and down-regulated expression of myocardial Cx43 were observed in all rabbits after modeling. After EA intervention and compared with the model group, the initial time of arrhythmia and Cx43 expression were obviously increased (P<0.01), and the duration of arrhythmia was significantly shortened in both deep and shallow needling groups (P<0.01). Compared with the shallow needling group, the Cx43 expression was increased in the deep needling group (P<0.01). H．E. staining showed disordered and wavy arrangement of myocardial fibers, with exudation of serous and erythrocytes in the myocardial interstitium in the model group, which was relatively mild in both needling groups. IHC showed disordered distribution of Cx43 in the ventricular myocytes and almost no obvious band-like distribution at the discs in rabbits of the model group, and abundant distribution of Cx43 in the sacral disc in the deep needling group, and strip-shaped, cluster-like, point-like, visible at both end-to-end connections and side-to-side connections in the shallow needling group. CONCLUSION: Both shallow and deep needling can significantly reduce the duration of arrhythmia in arrhythmia rabbits, which may be associated with its effect in up-regulating expression of myocardial Cx43 protein.

Tibetan medicine Ru-yi-Zhen-bao Pills exhibits anti-migraine effect through mediating PAG anti-nociceptive channel.

ETHNOPHARMACOLOGICAL RELEVANCE: Migraine is a disabling neurovascular disorder, which increases risk of cardiovascular events and is a social burden worldwide. The present first-line anti-migraine medications can cause overwhelming side-effects, of which one includes the onset of cardiovascular disease. As one of the marketed Tibetan drugs, Ru-yi-Zhen-bao Pills (RYZBP) have been clinically used to treat cardiovascular disorders and as anti-migraine medication. However, there is currently no research exploring the anti-migraine actions of RYZBP. AIM OF THE STUDY: The current research was designed to assess the anti-migraine roles of RYZBP and explore the underlying mechanisms in a nitroglycerin (NTG)-induced migraine rat model trial. MATERIALS AND METHODS: 120 rats were randomly divided into the following six groups of 20 rats each: normal control group, model control group, positive control group, and RYZBP high/medium/low-dose groups (Ru-yi-Zhen-bao Pills; TH 1.00 g/kg, TM 0.50 g/kg and TL 0.25 g/kg). All rats were administered intragastrically for 7 consecutive days, which were subcutaneously injected with the NTG (10 mg/kg) after the last gavage (except in the normal control group). 3min after NTG treatment, 30 rats (5 rats from each group) were anesthetized and devoted to electroencephalogram(EEG) testing, which was used to evaluate the analgesic effect of RYZBP. One hour after NTG treatment, the rest of the 90 rats (15 rats from each group) were anesthetized and midbrain tissue sample was dissected. The dissection was then washed with physiological saline and collected. The histopathological changes in the periaqueductal gray(PAG) of 5 tissue samples were determined by aematoxylin-eosin (H&E) staining, as well as an estimation of substance P (SP) and neurokinin 1 receptor (NK1R) expression through immunohistochemically staining(IHC). Another 5 midbrain preparations were carried out to evaluate calcitonin gene-related peptide (CGRP), proenkephalin (PENK), SP, and cholecystokinin (CCK) expressions by real-time quantitative polymerase chain reaction (RT-qPCR). The rest of the 5 brainstem tissues were then used to measure CCK, CGRP, and opioid peptide receptor (DORR) levels by western blotting(WB). RESULTS: In the EEG test, RYZBP (TM 0.50 g / kg) treatment transformed the EEG pain-wave of the NTG-induced migraine model rats in different time period. In the mechanism assay, compared with the model control group, RYZBP pretreatment reduced inflammatory cell infiltration, fibrosis and vacuolation of neuronal cells of PAG tissue seen by HE staining. IHC experiments further showed that RYZBPTM up-regulated SP expression levels and enhanced NK1R levels in the NTG-induced migraine rats (P < 0.05). Therapeutic administration of RYZBP also increased PENK mRNA expression and DORR protein level. Both RT-qPCR and western blotting trials indicated that RYZBP treatment significantly decreased CCK and CGRP expression levels (P < 0.01 or P < 0.05) in the NTG-induced migraine rats. CONCLUSIONS: RYZBP has the potential to be an effective anti-migraine treatment through suppressing the EEG pain-wave, increasing the levels of SP, PENK, DORR and reducing expression of CCK and CGRP. Mediating the PAG anti-nociceptive channel and inhibiting central sensitization were the two potential mechanisms, which offers further evidence for clinical therapy.