Optimization of ethanol extraction process for Yihuang powder by orthogonal experiment combined with AHP and GA-BP neural network / 中国药房

OBJECTIVE To optimize ethanol extraction process of Yihuang powder. METHODS An orthogonal experiment was designed by reflux extraction with ethanol volume fraction， liquid-to-material ratio， and extraction time as investigation factors. The parameters used were the contents of hesperidin， nobiletin， tangeretin， gallic acid， chebulagic acid， chebulinic acid， liquiritin， glycyrrhizin， eugenol， and the paste-forming rate. The analytic hierarchy process （AHP） was used to calculate the comprehensive score. The optimal ethanol extraction process parameters of Yihuang powder were determined by verifying the results predicted by orthogonal experiment and genetic algorithm （GA）-back propagation neural network （BP neural network）. RESULTS The optimal ethanol extraction process parameters， as optimized by orthogonal experiment， were as follows: ethanol volume fraction of 60%， liquid-solid ratio of 14∶1 （mL/g)， extraction time of 90 min， and extraction for 2 times. The comprehensive score obtained by verification was 79.19. Meanwhile， the optimal ethanol extraction process parameters， optimized by GA-BP neural network， were ethanol volume fraction of 65%， liquid-solid ratio of 14∶1 （mL/g )， extraction time of 60 min， and extraction for 2 times. The comprehensive score obtained by verification was 85.30， higher than the results obtained from orthogonal experiment. CONCLUSIONS The optimization method of orthogonal experiment combined with GA-BP neural network is superior to the traditional orthogonal experiment optimization method. The optimized ethanol extraction process of Yihuang powder is stable and reliable.

Establishment and genotype identification of hepatic stellate cell-specific Grk2 gene knockout mouse model / 中国药理学通报

Aim To establish a stable hepatic stellate cell ( HSC ) -specific G protein-coupled receptor kinase 2 ( GRK2 ) knockout mice and provide the important animal model for further studying the biological function of GRK2 in HSC. Methods The loxP-labeled Grk2 gene mouse (Grk2

Tricuspid annuloplasty surgery for functional tricuspid regurgitation: current state and perspectives / 中华胸心血管外科杂志

Tricuspid regurgitation(TR) is a malocclusion of the tricuspid lobes during systole, resulting in blood returning from the right ventricle to the right atrium during systole. Functional TR is not associated with clear tricuspid valve disease, but is secondary to left heart disease and is often accompanied by dilation of the tricuspid ring. The main treatment for TR is to reduce the enlarged ring with tricuspid valvuloplasty or to replace the diseased valve with tricuspid valve replacement. Tricuspid valvuloplasty is the most common and safest surgical method for functional TR, but the specific treatment strategies for TR are still controversial. This article reviews the diagnostic evaluation, surgical strategy and prognosis of TR treated by tricuspid valvuloplasty.

Phenotype-genotype analysis of the autosomal recessive hereditary hearing loss caused by OTOA variations / 中华耳鼻咽喉头颈外科杂志

Objective: To analyze the phenotypic-genotypic characteristics of hereditary deafness caused by OTOA gene variations. Methods: Family histories, clinical phenotypes and gene variations of six pedigrees were analyzed, which were diagnosed with hearing loss caused by OTOA gene variations at the PLA General Hospital from September 2015 to January 2022. The sequence variations were verified by Sanger sequencing and the copy number variations were validated by multiplex ligation-dependent probe amplification (MLPA) in the family members. Results: The hearing loss phenotype caused by OTOA variations ranged from mild to moderate in the low frequencies, and from moderate to severe in the high frequencies in the probands, which came from six sporadic pedigrees, among which a proband was diagnosed as congenital deafness and five were diagnosed as postlingual deafness. One proband carried homozygous variations and five probands carried compound heterozygous variations in OTOA gene. Nine pathogenic variations (six copy number variations, two deletion variations and one missense variation) and two variations with uncertain significance in OTOA were identified in total, including six copy number variations and five single nucleotide variants, and three of the five single nucleotide variants were firstly reported [c.1265G>T(p.Gly422Val),c.1534delG(p.Ala513Leufs*11) and c.3292C>T(p.Gln1098fs*)]. Conclusions: OTOA gene variations can lead to autosomal recessive nonsyndromic hearing loss. In this study, the hearing loss caused by OTOA defects mostly presents as bilateral, symmetrical, and postlingual, and that of a few presents as congenital. The pathogenic variations of OTOA gene are mainly copy number variations followed by deletion variations and missense variations.

Pregnancy Benefit of Acupuncture on in vitro Fertilization: A Systematic Review and Meta-Analysis / 中国结合医学杂志

BACKGROUND@#Currently, more and more infertility couples are opting for combined acupuncture to improve success rate of in vitro fertilization (IVF). However, evidence from acupuncture for improving IVF pregnancy outcomes remains a matter of debate.@*OBJECTIVE@#To quantitatively summarized the evidence of the efficacy of acupuncture among women undergoing IVF by means of systematic review and meta-analysis.@*METHODS@#Four English (PubMed, Web of Science, EMBASE, and Cochrane Register of Controlled Clinical Trials) and Four Chinese databases (Wanfang Databases, Chinese National Knowledge Infrastructure, Chinese Science and Technology Periodical Database, and SinoMed) were searched from database inception until July 2, 2023. Randomized controlled trials (RCTs) that evaluated the acupuncture's effects for women undergoing IVF were included. The subgroup analysis was conducted with respect to the age of participants, different acupuncture types, type of control, acupuncture timing, geographical origin of the study, whether or not repeated IVF failure, and acupuncture sessions. Sensitivity analyses were predefifined to explore the robustness of results. The primary outcomes were clinical pregnancy rate (CPR) and live birth rate (LBR), and the secondary outcomes were ongoing pregnancy rate and miscarriage rate. Random effects model with I2 statistics were used to quantify heterogeneity. Publication bias was estimated by funnel plots and Egger's tests.@*RESULTS@#A total of 58 eligible RCTs representing 10,968 women undergoing IVF for pregnant success were identifified. Pooled CPR and LBR showed a signifificant difference between acupuncture and control groups [69 comparisons, relative risk (RR) 1.19, 95% confifidence intervals (CI) 1.12 to 1.25, I2=0], extremely low evidence; 23 comparisons, RR 1.11, 95%CI 1.02 to 1.21, I2=14.6, low evidence, respectively). Only transcutaneous electrical acupoint stimulation showed a positive effect on both CPR (16 comparisons, RR 1.17, 95%CI 1.06 to 1.29; I2=0, moderate evidence) and LBR (9 comparisons, RR 1.20, 95%CI 1.04 to 1.37; I2=8.5, extremely low evidence). Heterogeneity across studies was found and no studies were graded as high-quality evidence.@*CONCLUSION@#Results showed that the convincing evidence levels on the associations between acupuncture and IVF pregnant outcomes were relatively low, and the varied methodological design and heterogeneity might inflfluence the fifindings. (Registration No. PROSPERO CRD42021232430).

Calculation of the Paternity Index for the Alleged Father Related to the Child's Mother / 法医学杂志

OBJECTIVES@#To derive the paternity index (PI) calculation formula of the alleged father (AF) when the AF is a relative (parent/child, siblings, grandparent/grandchild, uncle/nephew, first cousins) of the child's biological mother.@*METHODS@#For the case when the AF is related to the child's biological mother, the existence of the relationship in the numerator and denominator hypothesis of PI was considered. The genotype frequency of the AF was calculated by using the frequency formula in which the mother's genotype was considered, while the random male in the denominator was substituted as another relative of the mother's same rank. The PI calculation formula was derived to eliminate the effect of the relationship between AF and the child's biological mother.@*RESULTS@#When the AF and the biological mother have first, second and tertiary kinship, a more conservative PI was obtained from the PI calculation formula derived in this study compared with the PI calculation method which did not consider kinship.@*CONCLUSIONS@#The calculation method provided in this study can eliminate the effect of the relation of the AF and mother on the PI in incest cases, to obtain more accurate and conservative identification conclusions.

Study on relationship between platelet transfusion efficacy and KIR-HLA receptor-ligand compatibility / 中国输血杂志

【Objective】 To study the correlation between platelet transfusion efficacy and KIR receptor-HLA ligand. 【Methods】 Thirty-three leukemia patients with positive HLA antibody were tested for cross-matching with donor platelets. Platelets from suitable donors were selected for transfusion, and the 24-hour platelet corrected count increment (CCI) was used to determine the transfusion effect. KIR and ligand genotyping were performed on blood samples from patients and donors by PCR-SSP method, and the relationship between platelet transfusion effects and KIR receptor-HLA ligand was analyzed. 【Results】 In 74 occasions of platelet transfusion, 42 were ineffective and 32 were effective. When the donor had C2 gene and HLA-B Bw4-80T gene, the frequency of ineffective platelet transfusion in the recipient was 69.0% (29/42) and 52.4% (22/35), respectively, which was significantly higher than that in the effective group [25.0% (8/32) and 25.0% (8/32)]. When the donor had C1 gene, and the frequency of effective platelet transfusion in the recipient was 100.0%(32/32), which was higher than that in the ineffective group [83.3%(35/42)]. When the recipient-donor matching mode was KIR2DL1-C2 and KIR3DL1-(HLA-B Bw4-80T), the frequency of ineffective platelet transfusion was 69.0%(29/42) and 40.5%(22/42),higher than that of the effective group [25% (8/32) and 18.8% (6/32)]. When the recipient-donor matching model was KIR2DL3-C1, the rate of effective platelet transfusion in 32 patients (100.0%), which was higher than that (35 patients 83. 3%) in the ineffective group. When the mismatch mode of recipient iKIR+donor HLA ligand receptor was KIR2DL1-C2, the frequency of effective platelet transfusion in the recipient was 78.1% (25/32), which was much higher than that in the ineffective group [31.0% (13/42)]. When the mismatch mode was KIR3DL1-(HLA-B Bw4-80T), the rate of effective platelet transfusion in the recipient was 68.8% (22/32), which was higher than that in the ineffective group (42.9%, 18/42). The difference between the above groups was statistically significant(P<0.05). 【Conclusion】 HLA-C1 and HLA-C2 genes are the key factors affecting the efficacy of platelet transfusion.For platelet refractorines, HLA-C1 is the protective gene, while HLA-C2 and HLA-B Bw4-80T are the susceptible genes. The recipient iKIR+donor HLA ligand receptor model may play an important role in platelet refractoriness.

The protective effect of betelnut polyphenols on exercise-induced fatigue at high altitude and its network pharmacology in rats / 中国药理学通报

Aim: To explore the protective effect of betelnut polyphenols on high altitude exercise-induced fatigue in rats, and to select the main targets to carry out network pharmacology research to preliminarily explore its protective mechanism. Methods: We compared the protective effects of areca catechu polyphenols on high altitude exercise fatigue in rats in low, medium and high dose groups (400, 800, and 1600 mg·kg

Assessment of risk factors for bronchopulmonary dysplasia with pulmonary hypertension and construction of a prediction nomogram model / 中华儿科杂志

Objective: To explore the risk factors of pulmonary hypertension (PH) in premature infants with bronchopulmonary dysplasia (BPD), and to establish a prediction model for early PH. Methods: This was a retrospective cohort study. Data of 777 BPD preterm infants with the gestational age of <32 weeks were collected from 7 collaborative units of the Su Xinyun Neonatal Perinatal Collaboration Network platform in Jiangsu Province from January 2019 to December 2022. The subjects were randomly divided into a training cohort and a validation cohort at a ratio of 8∶2 by computer, and non-parametric test or χ2 test was used to examine the differences between the two retrospective cohorts. Univariate Logistic regression and multivariate logistic regression analyses were used in the training cohort to screen the risk factors affecting the PH associated with BPD. A nomogram model was constructed based on the severity of BPD and its risk factors,which was internally validated by the Bootstrap method. Finally, the differential, calibration and clinical applicability of the prediction model were evaluated using the training and verification queues. Results: A total of 130 among the 777 preterm infants with BPD had PH, with an incidence of 16.7%, and the gestational age was 28.7 (27.7, 30.0) weeks, including 454 males (58.4%) and 323 females (41.6%). There were 622 preterm infants in the training cohort, including 105 preterm infants in the PH group. A total of 155 patients were enrolled in the verification cohort, including 25 patients in the PH group. Multivariate Logistic regression analysis revealed that low 5 min Apgar score (OR=0.87, 95%CI 0.76-0.99), cesarean section (OR=1.97, 95%CI 1.13-3.43), small for gestational age (OR=9.30, 95%CI 4.30-20.13), hemodynamically significant patent ductus arteriosus (hsPDA) (OR=4.49, 95%CI 2.58-7.80), late-onset sepsis (LOS) (OR=3.52, 95%CI 1.94-6.38), and ventilator-associated pneumonia (VAP) (OR=8.67, 95%CI 3.98-18.91) were all independent risk factors for PH (all P<0.05). The independent risk factors and the severity of BPD were combined to construct a nomogram map model. The area under the receiver operating characteristic (ROC) curve of the nomogram model in the training cohort and the validation cohort were 0.83 (95%CI 0.79-0.88) and 0.87 (95%CI 0.79-0.95), respectively, and the calibration curve was close to the ideal diagonal. Conclusions: Risk of PH with BPD increases in preterm infants with low 5 minute Apgar score, cesarean section, small for gestational age, hamodynamically significant patent ductus arteriosus, late-onset sepsis, and ventilator-associated pneumonia. This nomogram model serves as a useful tool for predicting the risk of PH with BPD in premature infants, which may facilitate individualized early intervention.

Gastrin attenuates sepsis-induced myocardial dysfunction by down-regulation of TLR4 expression in macrophages

Myocardial dysfunction is the most serious complication of sepsis. Sepsis-induced myocardial dysfunction (SMD) is often associated with gastrointestinal dysfunction, but its pathophysiological significance remains unclear. The present study found that patients with SMD had higher plasma gastrin concentrations than those without SMD. In mice, knockdown of the gastrin receptor, cholecystokinin B receptor (Cckbr), aggravated lipopolysaccharide (LPS)-induced cardiac dysfunction and increased inflammation in the heart, whereas the intravenous administration of gastrin ameliorated SMD and cardiac injury. Macrophage infiltration plays a significant role in SMD because depletion of macrophages by the intravenous injection of clodronate liposomes, 48 h prior to LPS administration, alleviated LPS-induced cardiac injury in Cckbr-deficient mice. The intravenous injection of bone marrow macrophages (BMMs) overexpressing Cckbr reduced LPS-induced myocardial dysfunction. Furthermore, gastrin treatment inhibited toll-like receptor 4 (TLR4) expression through the peroxisome proliferator-activated receptor α (PPAR-α) signaling pathway in BMMs. Thus, our findings provide insights into the mechanism of the protective role of gastrin/CCKBR in SMD, which could be used to develop new treatment modalities for SMD.

Anti-inflammatory effects of acupuncture in the treatment of chronic obstructive pulmonary disease / 中西医结合学报

Numerous randomised controlled trials have suggested the positive effects of acupuncture on chronic obstructive pulmonary disease (COPD). However, the underlying therapeutic mechanisms of acupuncture for COPD have not been clearly summarized yet. Inflammation is central to the development of COPD. In this review, we elucidate the effects and underlying mechanisms of acupuncture from an anti-inflammatory perspective based on animal studies. Cigarette smoke combined with lipopolysaccharide is often used to establish animal models of COPD. Electroacupuncture can be an effective intervention to improve inflammation in COPD, and Feishu (BL13) and Zusanli (ST36) can be used as basic acupoints in COPD animal models. Different acupuncture types can regulate different types of inflammatory cytokines; meanwhile, different acupuncture types and acupoint options have similar effects on modulating the level of inflammatory cytokines. In particular, acupuncture exerts anti-inflammatory effects by inhibiting the release of inflammatory cells, inflammasomes and inflammatory cytokines. The main underlying mechanism through which acupuncture improves inflammation in COPD is the modulation of relevant signalling pathways: nuclear factor-κB (NF-κB) (e.g., myeloid differentiation primary response 88/NF-κB, toll-like receptor-4/NF-κB, silent information regulator transcript-1/NF-κB), mitogen-activated protein kinase signalling pathways (extracellular signal-regulated kinase 1/2, p38 and c-Jun NH2-terminal kinase), cholinergic anti-inflammatory pathway, and dopamine D2 receptor pathway. The current synthesis will be beneficial for further research on the effect of acupuncture on COPD inflammation. Please cite this article as: Jiang LH, Li PJ, Wang YQ, Jiang ML, Han XY, Bao YD, Deng XL, Wu WB, Liu XD. Anti-inflammatory effects of acupuncture in the treatment of chronic obstructive pulmonary disease. J Integr Med. 2023; 21(6): 518-527.

Hyperosmolarity promotes macrophage pyroptosis by driving the glycolytic reprogramming of corneal epithelial cells in dry eye disease / 医学前沿

Tear film hyperosmolarity plays a core role in the development of dry eye disease (DED) by mediating the disruption of ocular surface homeostasis and triggering inflammation in ocular surface epithelium. In this study, the mechanisms involving the hyperosmolar microenvironment, glycolysis mediating metabolic reprogramming, and pyroptosis were explored clinically, in vitro, and in vivo. Data from DED clinical samples indicated that the expression of glycolysis and pyroptosis-related genes, including PKM2 and GSDMD, was significantly upregulated and that the secretion of IL-1β significantly increased. In vitro, the indirect coculture of macrophages derived from THP-1 and human corneal epithelial cells (HCECs) was used to discuss the interaction among cells. The hyperosmolar environment was found to greatly induce HCECs' metabolic reprogramming, which may be the primary cause of the subsequent inflammation in macrophages upon the activation of the related gene and protein expression. 2-Deoxy-d-glucose (2-DG) could inhibit the glycolysis of HCECs and subsequently suppress the pyroptosis of macrophages. In vivo, 2-DG showed potential efficacy in relieving DED activity and could significantly reduce the overexpression of genes and proteins related to glycolysis and pyroptosis. In summary, our findings suggested that hyperosmolar-induced glycolytic reprogramming played an active role in promoting DED inflammation by mediating pyroptosis.

A Prediction Model Based on the Risk Factors Associated with Pathological Upgrading in Patients with Early-Stage Gastric Neoplasms Diagnosed by Endoscopic Forceps Biopsy

Background/Aims@#The discrepancies between the diagnosis of preoperative endoscopic forceps biopsy (EFB) and endoscopic submucosal dissection (ESD) in patients with early gastric neoplasm (EGN) exist objectively. Among them, pathological upgrading directly influences the accuracy and appropriateness of clinical decisions. The aims of this study were to investigate the risk factors for the discrepancies, with a particular focus on pathological upgrading and to establish a prediction model for estimating the risk of pathological upgrading after EFB. @*Methods@#We retrospectively collected the records of 978 patients who underwent ESD from December 1, 2017 to July 31, 2021 and who had a final histopathology determination of EGN. A nomogram to predict the risk of pathological upgrading was constructed after analyzing subgroup differences among the 901 lesions enrolled. @*Results@#The ratio of pathological upgrading was 510 of 953 (53.5%). Clinical, laboratorial and endoscopic characteristics were analyzed using univariable and binary multivariable logistic regression analyses. A nomogram was constructed by including age, history of chronic atrophic gastritis, symptoms of digestive system, blood high density lipoprotein concentration, macroscopic type, pathological diagnosis of EFB, uneven surface, remarkable redness, and lesion size. The C-statistics were 0.804 (95% confidence interval, 0.774 to 0.834) and 0.748 (95% confidence interval, 0.664 to 0.832) in the training and validation set, respectively. We also built an online webserver based on the proposed nomogram for convenient clinical use. @*Conclusions@#The clinical value of identifying the preoperative diagnosis of EGN lesions is limited when using EFB separately. We have developed a nomogram that can predict the probability of pathological upgrading with good calibration and discrimination value.

Circular RNA circRSF1 binds to HuR to promote radiation-induced inflammatory phenotype in hepatic stellate cells / 南方医科大学学报

OBJECTIVE@#To investigate whether circular RNA circRSF1 regulates radiation-induced inflammatory phenotype of hepatic stellate cells (HSCs) by binding to HuR protein and repressing its function.@*METHODS@#Human HSC cell line LX2 with HuR overexpression or knockdown was exposed to 8 Gy X-ray irradiation, and the changes in the expression of inflammatory factors (IL-1β, IL-6 and TNF-α) were detected by qRT-PCR. The expressions of IκBα and phosphorylation of NF-κB were detected with Western blotting. The binding of circRSF1 to HuR was verified by RNA pull-down assay and RNA-binding protein immunoprecipitation (RIP). The expressions of inflammatory factors, IκBα and the phosphorylation of NF-κB were detected after modifying the interaction between circRSF1 and HuR.@*RESULTS@#Knockdown of HuR significantly up- regulated the expressions of IL-1β, IL-6 and TNF-α, decreased IκBα expression and promoted NF-κB phosphorylation in irradiated LX2 cells, whereas overexpression of HuR produced the opposite changes (P < 0.05). Overexpression or knockdown of circRSF1 did not significantly affect the expression of HuR. RNA pull-down and RIP experiments confirmed the binding between circRSF1 and HuR. Overexpression of circRSF1 significantly reduced the binding of HuR to IκBα and down-regulated the expression of IκBα (P < 0.05). Overexpression of circRSF1 combined with HuR overexpression partially reversed the up-regulation of the inflammatory factors, down-regulated IκBα expression and increased phosphorylation of NFκB in LX2 cells, while the opposite effects were observed in cells with knockdown of both circRSF1 and HuR (P < 0.05).@*CONCLUSION@#circRSF1 reduces IκBα expression by binding to HuR to promote the activation of NF-κB pathway, thereby enhancing radiation- induced inflammatory phenotype of HSCs.

Characteristics of plasma Epstein-Barr virus DNA in children with primary infection / 中华儿科杂志

Objective: To explore the characteristics of plasma Epstein-Barr virus (EBV) DNA in primary infection in pediatric cases. Methods: The laboratory and clinical data of 571 children diagnosed with EBV primary infection in Children's Hospital of Fudan University during September 1st, 2017 to September 30th, 2018 were retrospectively analyzed. According to the results of plasma EBV DNA, they were divided into positive group and negative group. According to the EBV DNA, they were devided into high plasma virol load group and low plasma virol load group. The Chi-square test, Wilcoxon rank sum test were used to compare the differences between groups. Results: Among the 571 children with EBV primary infection, 334 were males and 237 were females. The age of first diagnosis was 3.8 (2.2, 5.7) years. There were 255 cases in positive group and 316 cases in negative group. The percentage of cases with fever,hepatomegaly and (or) splenomegaly, elevated transaminase in the positive group were higher than those in the negative group (235 cases (92.2%) vs. 255 cases (80.7%), χ2=15.22, P<0.001; 169 cases (66.3%) vs. 85 cases (26.9%), χ2=96.80, P<0.001; and 144 cases (56.5%) vs. 120 cases (38.0%), χ2=18.27, P<0.001; respectively).In the positive group, 70 cases were followed up for 46 (27, 106) days, 68 cases (97.1%) turned negative within 28 days, with the exception of 2 cases (2.9%) developed chronic active EBV infection by follow-up revision.There were 218 cases in high plasma viral DNA copies group and 37 cases in low copies group. More cases presented with elevated transaminases in the high plasma viral DNA copies group than those in the low group (75.7% (28/37) vs. 56.0%(116/207), χ2=5.00, P=0.025).Both the positive rate of EBV DNA in peripheral blood leukocytes (84.2% (266/316) vs. 44.7% (255/571), χ2=76.26, P<0.001) and the copies of EBV DNA (7.0×107 (1.3×107, 3.0×108) vs. 3.1×106 (1.6×106, 6.1×106) copies /L, Z=15.23, P<0.001) were higher than that of plasma. Conclusions: In immunocompetent pediatric cases diagnosed as EBV primary infection, cases with positive plasma EBV DNA were prone to have fever, hepatomegaly and (or) splenomegaly, and elevated transaminase than those with negative plasma viral DNA. The plasma EBV DNA usually turns negative within 28 days after initial diagnosis.Most cases with high viral load in plasma showed elevated aminotransferase.

Yinlai Decoction Protects Microstructure of Colon and Regulates Serum Level of D-Lactic Acid in Pneumonia Mice Fed with High-Calorie and High-Protein Diet / 中国结合医学杂志

OBJECTIVE@#To investigate the effect of Yinlai Decoction (YD) on the microstructure of colon, and activity of D-lactic acid (DLA) and diamine oxidase (DAO) in serum of pneumonia mice model fed with high-calorie and high-protein diet (HCD).@*METHODS@#Sixty male Kunming mice were randomly divided into 6 groups by the random number table method: normal control, pneumonia, HCD, HCD with pneumonia (HCD-P), YD (229.2 mg/mL), and dexamethasone (15.63 mg/mL) groups, with 10 in each group. HCD mice were fed with 52% milk solution by gavage. Pneumonia mice was modeled with lipopolysaccharide inhalation and was fed by gavage with either the corresponding therapeutic drugs or saline water, twice daily, for 3 days. After hematoxylin-eosin staining, the changes in the colon structure were observed under light microscopy and transmission electron microscope, respectively. Enzyme-linked immunosorbent assay was used to detect the protein levels of DLA and DAO in the serum of mice.@*RESULTS@#The colonic mucosal structure and ultrastructure of mice in the normal control group were clear and intact. The colonic mucosal goblet cells in the pneumonia group tended to increase, and the size of the microvilli varied. In the HCD-P group, the mucosal goblet cells showed a marked increase in size with increased secretory activity. Loose mucosal epithelial connections were also observed, as shown by widened intercellular gaps with short sparse microvilli. These pathological changes of intestinal mucosa were significantly reduced in mouse models with YD treatment, while there was no significant improvement after dexamethasone treatment. The serum DLA level was significantly higher in the pneumonia, HCD, and HCD-P groups as compared with the normal control group (P<0.05). Serum DLA was significantly lower in the YD group than HCD-P group (P<0.05). Moreover, serum DLA level significantly increased in the dexamethasone group as compared with the YD group (P<0.01). There was no statistical significance in the serum level of DAO among groups (P>0.05).@*CONCLUSIONS@#YD can protect function of intestinal mucosa by improving the tissue morphology of intestinal mucosa and maintaining integrity of cell connections and microvilli structure, thereby reducing permeability of intestinal mucosa to regulate the serum levels of DLA in mice.

Shexiang Tongxin Dropping Pill Allieviates Heart Failure via Extracellula Matrix-Receptor Interaction Pathways Based on RNA-Seq Transcriptomics and Experimental Studies / 中国结合医学杂志

OBJECTIVE@#To investigate the protective mechanisms of Chinese medicine Shexiang Tongxin Dropping Pills (STDP) on heart failure (HF).@*METHODS@#Isoproterenol (ISO)-induced HF rat model and angiotensin II (Ang II)-induced neonatal rat cardiac fibroblast (CFs) model were used in the present study. HF rats were treated with and without STDP (3 g/kg). RNA-seq was performed to identify differentially expressed genes (DEGs). Cardiac function was evaluated by echocardiography. Hematoxylin and eosin and Masson's stainings were taken to assess cardiac fibrosis. The levels of collagen I (Col I) and collagen III (Col III) were detected by immunohistochemical staining. CCK8 kit and transwell assay were implemented to test the CFs' proliferative and migratory activity, respectively. The protein expressions of α-smooth muscle actin (α-SMA), matrix metalloproteinase-2 (MMP-2), MMP-9, Col I, and Col III were detected by Western blotting.@*RESULTS@#The results of RNA-seq analysis showed that STDP exerted its pharmacological effects on HF via multiple signaling pathways, such as the extracellular matrix (ECM)-receptor interaction, cell cycle, and B cell receptor interaction. Results from in vivo experiments demonstrated that STDP treatment reversed declines in cardiac function, inhibiting myocardial fibrosis, and reversing increases in Col I and Col III expression levels in the hearts of HF rats. Moreover, STDP (6, 9 mg/mL) inhibited the proliferation and migration of CFs exposed to Ang II in vitro (P<0.05). The activation of collagen synthesis and myofibroblast generation were markedly suppressed by STDP, also the synthesis of MMP-2 and MMP-9, as well as ECM components Col I, Col III, and α-SMA were decreased in Ang II-induced neonatal rats' CFs.@*CONCLUSIONS@#STDP had anti-fibrotic effects in HF, which might be caused by the modulation of ECM-receptor interaction pathways. Through the management of cardiac fibrosis, STDP may be a compelling candidate for improving prognosis of HF.

Predictive validation of existing bleeding and thromboembolic scores in elderly patients with comorbid atrial fibrillation and acute coronary syndrome / 老年心脏病学杂志（英文版）

BACKGROUND@#The validation of various risk scores in elderly patients with comorbid atrial fibrillation (AF) and acute coronary syndrome (ACS) has not been reported. The present study compared the predictive performance of existing risk scores in these patients.@*METHODS@#A total of 1252 elderly patients with AF and ACS comorbidities (≥ 65 years old) were consecutively enrolled from January 2015 to December 2019. All patients were followed up for one year. The predictive performance of risk scores in predicting bleeding and thromboembolic events was calculated and compared.@*RESULTS@#During the 1-year follow-up, 183 (14.6%) patients had thromboembolic events, 198 (15.8%) patients had BARC class ≥ 2 bleeding events, and 61 (4.9%) patients had BARC class ≥ 3 bleeding events. For the BARC class ≥ 3 bleeding events, discrimination of the existing risk scores was low to moderate, PRECISE-DAPT (C-statistic: 0.638, 95% CI: 0.611-0.665), ATRIA (C-statistic: 0.615, 95% CI: 0.587-0.642), PARIS-MB (C-statistic: 0.612, 95% CI: 0.584-0.639), HAS-BLED (C-statistic: 0.597, 95% CI: 0.569-0.624) and CRUSADE (C-statistic: 0.595, 95% CI: 0.567-0.622). However, the calibration was good. PRECISE-DAPT showed a higher integrated discrimination improvement (IDI) than PARIS-MB, HAS-BLED, ATRIA, and CRUSADE (P < 0.05) and the best decision curve analysis (DCA). For thromboembolic events, the discrimination of GRACE (C-statistic: 0.636, 95% CI: 0.608-0.662) was higher than CHA2DS2-VASc (C-statistic: 0.612, 95% CI: 0.584-0.639), OPT-CAD (C-statistic: 0.602, 95% CI: 0.574-0.629) and PARIS-CTE (C-statistic: 0.595, 95% CI: 0.567-0.622). The calibration was good. Compared to OPT-CAD and PARIS-CTE, the IDI of the GRACE score slightly improved (P < 0.05). However, NRI analysis showed no significant difference. DCA showed that the clinical practicability of thromboembolic risk scores was similar.@*CONCLUSIONS@#The discrimination and calibration of existing risk scores in predicting 1-year thromboembolic and bleeding events were unsatisfactory in elderly patients with comorbid AF and ACS. PRECISE-DAPT showed higher IDI and DCA than other risk scores in predicting BARC class ≥ 3 bleeding events. The GRACE score showed a slight advantage in predicting thrombotic events.

Intestinal and pharyngeal microbiota in early neonates: an analysis based on high-throughput sequencing / 中国当代儿科杂志

OBJECTIVES@#To investigate the distribution characteristics and correlation of intestinal and pharyngeal microbiota in early neonates.@*METHODS@#Full-term healthy neonates who were born in Shanghai Pudong New Area Maternal and Child Health Hospital from September 2021 to January 2022 and were given mixed feeding were enrolled. The 16S rRNA sequencing technique was used to analyze the stool and pharyngeal swab samples collected on the day of birth and days 5-7 after birth, and the composition and function of intestinal and pharyngeal microbiota were analyzed and compared.@*RESULTS@#The diversity analysis showed that the diversity of pharyngeal microbiota was higher than that of intestinal microbiota in early neonates, but the difference was not statistically significant (P>0.05). On the day of birth, the relative abundance of Proteobacteria in the intestine was significantly higher than that in the pharynx (P<0.05). On days 5-7 after birth, the relative abundance of Actinobacteria and Proteobacteria in the intestine was significantly higher than that in the pharynx (P<0.05), and the relative abundance of Firmicutes in the intestine was significantly lower than that in the pharynx (P<0.05). At the genus level, there was no significant difference in the composition of dominant bacteria between the intestine and the pharynx on the day of birth (P>0.05), while on days 5-7 after birth, there were significant differences in the symbiotic bacteria of Streptococcus, Staphylococcus, Rothia, Bifidobacterium, and Escherichia-Shigella between the intestine and the pharynx (P<0.05). The analysis based on the database of Clusters of Orthologous Groups of proteins showed that pharyngeal microbiota was more concentrated on chromatin structure and dynamics and cytoskeleton, while intestinal microbiota was more abundant in RNA processing and modification, energy production and conversion, amino acid transport and metabolism, carbohydrate transport and metabolism, coenzyme transport and metabolism, and others (P<0.05). The Kyoto Encyclopedia of Genes and Genomes analysis showed that compared with pharyngeal microbiota, intestinal microbiota was more predictive of cell motility, cellular processes and signal transduction, endocrine system, excretory system, immune system, metabolic diseases, nervous system, and transcription parameters (P<0.05).@*CONCLUSIONS@#The composition and diversity of intestinal and pharyngeal microbiota of neonates are not significantly different at birth. The microbiota of these two ecological niches begin to differentiate and gradually exhibit distinct functions over time.

Research on applying genetic and environmental risk score in risk-adapted colorectal cancer screening / 中华流行病学杂志

Objective: To evaluate the effectiveness of a risk-adapted colorectal cancer screening strategy constructed utilizing genetic and environmental risk score (ERS). Methods: A polygenic risk score (PRS) was constructed based on 20 previously published single nucleotide polymorphisms for colorectal cancer in East Asian populations, using 2 160 samples with MassARRAY test results from a multicenter randomized controlled trial of colorectal cancer screening in China. The ERS was calculated using the Asia-Pacific Colorectal Screening Score system. Logistic regression was used to analyze the association between PRS alone and PRS combined with ERS and colorectal neoplasms risk, respectively. We also designed a risk-adapted screening strategy based on PRS and ERS (high-risk participants undergo a single colonoscopy, low-risk participants undergo an annual fecal immunochemical test, and those with positive results undergo further diagnostic colonoscopy) and compared its effectiveness with the all-acceptance colonoscopy strategy. Results: The high PRS group had a 26% increased risk of colorectal neoplasms compared with the low PRS group (OR=1.26, 95%CI: 1.03-1.54, P=0.026). Participants with the highest PRS and ERS were 3.03 times more likely to develop advanced colorectal neoplasms than those with the lowest score (95%CI: 1.87-4.90, P<0.001). As the risk-adapted screening simulation reached the third round, the detection rate of the PRS combined with ERS strategy was not statistically different from the all-acceptance colonoscopy strategy (8.79% vs. 10.46%, P=0.075) and had a higher positive predictive value (14.11% vs. 10.46%, P<0.001) and lower number of colonoscopies per advanced neoplasms detected (7.1 vs. 9.6, P<0.001). Conclusion: The risk-adapted screening strategy combining PRS and ERS helps achieve population risk stratification and better effectiveness than the traditional colonoscopy-based screening strategy.