Mechanism of Dahuang Mudantang in Improving Pancreatic Injury in Rats with Acute Pancreatitis of Dampness-heat in Large Intestine Syndrome Based on Network Pharmacology and Experimental Verification / 中国实验方剂学杂志

ObjectiveTo reveal the intervention effect of Dahuang Mudantang on pancreatic injury in rats with acute pancreatitis （AP） of dampness-heat in large intestine syndrome and explore its possible mechanism based on network pharmacology. MethodNinety-six SPF-grade Wistar rats were randomly divided into the following six groups： a blank group， a model group， low-， medium-， and high-dose Dahuang Mudantang groups （3.5， 7， and 14 g·kg-1）， and a Qingyi Lidan granules group （3 g·kg-1）， with 16 rats in each group. The AP model of dampness-heat in large intestine syndrome was induced in rats except for those in the blank group by "high-temperature and high-humidity environment + high-sugar and high-fat diet + retrograde injection of 5% sodium taurocholate into the pancreaticobiliary duct". The blank and model groups received equal volumes of distilled water by gavage， while the treatment groups were administered Dahuang Mudantang or Qingyi Lidan granules 1 hour before modeling， and 12 and 24 hours after modeling. Samples were collected 1 hour after the last administration. The general conditions of the rats were observed. The AP model of dampness-heat in large intestine syndrome was evaluated. Serum amylase （AMS） and C-reactive protein （CRP） levels were determined using biochemical methods. Pancreatic tissue morphology was observed using hematoxylin-eosin （HE） staining. Network pharmacology was employed to predict potential targets of Dahuang Mudantang in the intervention in AP， and molecular biology technique was used to verify relevant targets. ResultCompared with the blank group， the model group exhibited lethargy， unkempt fur， loose and foul-smelling stools， elevated anal temperature with arching and twisting reactions， significantly increased serum levels of AMS and CRP （P<0.05）， abnormal pancreatic ductules， disordered interlobular spaces， and inflammatory cell infiltration in histopathological examination， as well as pathological changes including pancreatic acinar cell swelling， congestion， and necrosis. Compared with the model group， the treatment groups showed varying degrees of improvement in general survival conditions， reduced twisting reactions， visibly improved stool characteristics， reduced pancreatic tissue edema and necrosis， decreased serum AMS and CRP levels （P<0.05）， with the high-dose Dahuang Mudantang group showing the most pronounced effects （P<0.05）. Network pharmacology prediction indicated that hederagenin， β-sitosterol， and quercetin were the most widely connected active compounds with disease targets. Protein-protein interaction （PPI） network analysis revealed that protein kinase B （Akt）， tumor protein P53 （TP53）， tumor necrosis factor （TNF）， interleukin-6 （IL-6）， transcription factor （JUN）， vascular endothelial growth factor α （VEGFα）， interleukin-1β （IL-1β）， and vascular cell adhesion molecule-1 （VCAM1） were key targets in the "drug-disease" interaction. KEGG enrichment analysis suggested that the response of the mitogen activated protein kinase （MAPK） signaling pathway might be a core mechanism for DHMDT in the intervention in AP. Molecular biology analysis showed that compared with the blank group， the model group had significantly increased levels of TNF-α， IL-6， and VCAM-1 in pancreatic tissue （P<0.05）， as well as significantly elevated expression levels of p38 mitogen-activated protein kinase （p38 MAPK）， mitogen-activated protein kinase-activated protein kinase 2 （MK2）， and human antigen R （HUR） genes and proteins （P<0.05）. Compared with the model group， the treatment groups exhibited decreased levels of TNF-α， IL-6， and VCAM-1 in pancreatic tissue （P<0.05）， reduced expression levels of p38 MAPK， MK2， and HUR genes and proteins， with the high-dose Dahuang Mudantang group showing the most pronounced effects （P<0.05）. ConclusionDahuang Mudantang activates and regulates the p38 MAPK/MK2/HUR signaling pathway to suppress the release of inflammatory factors， thereby improving pancreatic injury.

Comparison of results of prenatal diagnosis by different techniques for fetuses with increased nuchal translucency / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of chromosomal microarray analysis (CMA) and trio-whole exome sequencing (trio-WES) for fetuses with increased nuchal translucency (NT) thickness.@*METHODS@#Sixty two pregnant women who had visited Urumqi Maternal and Child Care Health Hospital between June 2018 and June 2020 for NT ≥ 3.0 mm at 11 ~ 13+6 gestational weeks were selected as study subjects. Relevant clinical data were collected. The patients were divided into 3.0 ~ ＜3.5 mm (n = 33) and ≥3.5 mm groups (n = 29). Chromosome karyotyping analysis and chromosomal microarray analysis were carried out. And trio-WES analysis was performed on 15 samples with NT thickening but negative CMA results. The distribution and incidence of chromosomal abnormalities in the two groups were compared by using chi-square test.@*RESULTS@#The median age of the pregnant women was 29 years old (22 ~ 41 years old), the median thickness of NT was 3.4 mm (3.0 ~ 9.1 mm), and the median gestational age at the detection was 13+4 weeks (11+5 ~ 13+6 weeks). Chromosome karyotyping analysis has detected 12 cases of aneuploidies and 1 case of derivative chromosome. The detection rate was 20.97% (13/62). CMA has detected 12 cases of aneuploidies, 1 case of pathogenic CNV and 5 cases of variant of uncertain significance (VUS), with a detection rate of 29.03% (18/62). The aneuploidy rate for the NT ≥ 3.5 mm group was higher than that for the 3.0 ≤ NT < 3.5 mm group [3.03% (1/33) vs. 41.38% (12/29), χ² = 13.698, P < 0.001]. There was no statistically significant difference between the two groups in the detection rate of fetal pathogenic CNV and VUS (χ² = 0.028, P > 0.05). Trio-WES analysis of 15 samples with negative CMA result and no structural abnormality has identified 6 heterozygous variants, including SOS1: c.3542C>T (p.A1181V) and c.3817C>G (p.L1273V), COL2A1: c.436C>T (p.P146S) and c.3700G>A (p.D1234N), LZTR1: c.1496T>C (p.V499A), and BRAF: c.64G>A (p.D22N), respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), all of the variants were rated as VUS.@*CONCLUSION@#NT thickening can indicate chromosome abnormality, and CMA and trio-WES may be used for the prenatal diagnosis.

Dahuang Mudantang Alleviates Intestinal Injury in Rat Model of Acute Pancreatitis by Regulating HMGB1/RAGE/NF-κB Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Dahuang Mudantang in alleviating the intestinal injury in the rat model of acute pancreatitis via the high-mobility group box 1 （HMGB1）/receptor for advanced glycation endproduct （RAGE）/nuclear factor-κB （NF-κB） signaling pathway. MethodOne hundred and twenty SPF-grade Wistar rats received retrograde injection of 5% sodium taurocholate into the biliopancreatic duct for the modeling of intestinal injury in acute pancreatitis. The rats were randomized into blank， model， low-， medium-， and high-dose （3.5， 7， 14 g·kg-1， administrated by gavage） Dahuang Mudantang， and octreotide （1×10-5 g·kg-1， subcutaneous injection） groups （n=20）. The rats in blank and model groups received equal volume of distilled water by gavage. Drugs were administered 1 h before and every 12 h after modeling， and samples were collected 24 h after modeling. The general status of the rats was observed. The biochemical methods were employed to measure the levels of amylase （AMS） and C-reactive protein （CRP） in the serum. The enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of tumor necrosis factor （TNF）-α， interleukin （IL）-1β， and IL-6 in the colon tissue. The morphological changes of pancreatic and colon tissues were observed by hematoxylin-eosin （HE） staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were employed to measure the expression levels of HMGB1， RAGE， inhibitor of NF-κB kinase （IKK）， and NF-κB suppressor protein α（IκBα）in the colon tissue. ResultThe rats in the model group showed poor general survival， writhing response， reduced frequency of defecation， and dry stool. The symptoms of rats in the model group were mitigated in each treatment group， and the high-dose Dahuang Mudantang showed the most significant effect. Compared with the normal group， the model group had elevated AMS and CRP levels （P<0.05）， which were lowered by Dahuang Mudantang （P<0.05）， especially that at the high dose （P<0.05）. Compared with the normal group， the modeling elevated that levels of TNF-α， IL-1β， and IL-6 （P<0.05）. Such elevations were lowered by Dahuang Mudantang （P<0.05）， and the high-dose group and the octreotide group showed better performance （P<0.05）. The modeling caused necrotic， congested， and destructed pancreatic and colonic tissues， which were ameliorated by the drugs， especially high-dose Dahuang Mudantang. Compared with the normal group， the modeling up-regulated the mRNA levels of HMGB1， RAGE， IKK， IκBα， and NF-κB （P<0.05）. Compared with the model group， Dahuang Mudantang and octreotide down-regulated the mRNA levels of HMGB1， RAGE， IKK， IκBα， and NF-κB （P<0.05）， and the high-dose Dahuang Mudantang demonstrated the best performance （P<0.05）. Western blot results showed a trend consistent with the results of Real-time PCR. ConclusionDahuang Mudantang can improved the general status， reduce inflammation， and alleviate histopathological changes in the pancreatic and colon tissues in the rat model of acute pancreatitis by inhibiting the HMGB1/RAGE/NF-κB signaling pathway.

Chemical genomics reveals inhibition of breast cancer lung metastasis by Ponatinib via c-Jun

Metastasis is the leading cause of human cancer deaths. Unfortunately, no approved drugs are available for anti-metastatic treatment. In our study, high-throughput sequencing-based high-throughput screening (HTS) and a breast cancer lung metastasis (BCLM)-associated gene signature were combined to discover anti-metastatic drugs. After screening of thousands of compounds, we identified Ponatinib as a BCLM inhibitor. Ponatinib significantly inhibited the migration and mammosphere formation of breast cancer cells in vitro and blocked BCLM in multiple mouse models. Mechanistically, Ponatinib represses the expression of BCLM-associated genes mainly through the ERK/c-Jun signaling pathway by inhibiting the transcription of JUN and accelerating the degradation of c-Jun protein. Notably, JUN expression levels were positively correlated with BCLM-associated gene expression and lung metastases in breast cancer patients. Collectively, we established a novel approach for the discovery of anti-metastatic drugs, identified Ponatinib as a new drug to inhibit BCLM and revealed c-Jun as a crucial factor and potential drug target for BCLM. Our study may facilitate the therapeutic treatment of BCLM as well as other metastases.

Predictive value of coagulation state on angiographic no-reflow during percutaneous coronary intervention for patients with acute myocardial infarction / 实用医学杂志

Objective To investigate the predictive value of coagulation state on the occurrence of no-reflow phenomenon after primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). Methods A total of 187 consecutive patients with the first AMI underwent PCI within 12h post-onset of symptom. The clinical features and angiographic findings were collected. According to the thrombolysis in myocardial infarction (TIMI) flow grade with related artery and myocardial blush grade(MBG), the patients were divided into the no-reflow group (TIMI ≤ 2, or MBG ≤ 1) and the normal reflow group. Blood samples were taken immediately on admission before coronary angiography. The levels of plasma von Willebrand factor(vWF), P-selectin(Ps) and Tissue factor(TF) were measured by enzyme-linked immunosorbent assay. Results 23.5%patients of 187 patients developed the no-reflow phenomenon. The plasma level of vWF and Ps and TF were (4 574 ± 1 677) U/L and (16.8 ± 5.1) ng/mL and (283 ± 81) ng/L in the no-reflow group, and (4 074 ± 1 063) U/L and (14.8 ± 4.2) ng/mL and (254 ± 54) ng/L in the normal group, with significant differences (P = 0.020, 0.010 and 0.007, respectively). The hypercoagulation patients in the no-reflow group were much more than patients in the normal reflow group (P = 0.003). Multivariate stepwise logistic regression analysis revealed that hypercoagulation was independent predictor of no-reflow phenomenon ( OR = 2 . 361 , 95%CI 1 . 083 ~ 5 . 148 , P = 0.031). Conclusion The high levels of plasma vWF, Ps and TF present the evidences of hypercoagulation, which might imply the development of no-reflow after PCI.

Evaluation of the Combined Use of Ultrasound Elastography and Color Doppler in the Diagnosis and TNM Classification of Breast Cancer / 天津医药

Objective To investigate the effect of the combined use of ultrasound (US) elastography and color Dop-pler on the differential diagnosis and TNM staging of benign or malignant breast neoplasm. Methods A cohort of 58 biop-sy-proved cases, who underwent US elastographic and Doppler US imaging, were included in the current study. The pathological results after operation were considered the‘gold standard’of diagnosis. ROC curves were used to compare the changing rates of the diameter and area, elastographic indices and Doppler blood flow score in diagnosis of breast cancer. Re-sults Compared with other indices, the area changing rate showed the highest diagnostic ability with the AUC=0.914. More-over, the combined use of the elastography and color Doppler US increased the AUC to 0.981. The elastographic indices for neoplasm in the advanced-stage (stageⅡ~Ⅳ) were high than those of early-stage (stage 0~Ⅰ). The elastographic and Dop-pler scores increased with the progress of the TNM stages. Conclusion The changing rate of elastographic area can be used to accurately diagnose the breast neoplasm. Moreover, the combined use of US elastography and color Doppler US can in-crease the accuracy of the diagnosis, and may also provide useful information for the TNM staging.

Clinical study on endoscopic variceal ligation combined with endoscopic variceal sclerosis for treating patients with esophageal variceal bleeding / 中国医师进修杂志

Objective To investigate the clinical efficacy and safety of endoscopic variceal ligation (EVL) combined with endoscopic variceal sclerosis (EVS) for treating patients with esophageal variceal bleeding (EVB).Methods Ninety patients with EVB were divided into observation group and control group by treatment methods with 45 patients each.The observation group was given EVL combined with EVS and the control group was given EVL.The elimination of varicosity after the first treatment,time and times required to eliminate,rehaemorrhagia,varicosity recurrence,complication and prognosis of the 2 groups were observed.Results The elimination rate of varicosity of observation group was 97.8％(44/45),the control group was 93.3％(42/45),there was no significant difference (P＞ 0.05).The elimination rote of varicosity after the first treatment of observation group was significantly higher than that of control group,the time and times required to eliminate were significantly lower than those of control group [71.1％(32/45) vs.48.9％(22/45),(17.24±5.65) d vs.(36.01 ± 11.81) d,(1.42 ±0.47) times vs.(1.87 ±0.61) times,P ＜ 0.05 or ＜0.01].The rates of early-onset rehaemorrhagia,delayed rehaemorrhagia and varicosity recurrence of observation group were significantly lower than those of control group [4.4％(2/45) vs.17.8％(8/45),6.7％(3/45) vs.22.2％ (10/45),2.2％ (1/45) vs.22.2％ (10/45),P ＜0.05].The rate of complication of observation group was significantly lower than that of control group [11.1％ (5/45) vs.42.2％ (19/45),P ＜0.01].Conclusion The EVL combined with EVS is an effective method for emergency hemostasis and preventing rehaemorrhagia in the patients with EVB.

Effect of titanium plate internal fixation in the treatment of comminuted calcaneal fractures / 中国基层医药

Objective To evaluate operative methods and the clinical effect for comminuted calcaneal fractures.Methods 21 cases(24 feet)of comminuted calcaneal fractures were treated by one stage bone grafting plus open reduction and internal fixation with plastic calcaneus titanium plate.The fractures were classified according to the Sanders system into Sanders Ⅱ,Ⅲ and Ⅳ subgroups.Results All cases were followed up for 9～20 months(14months in average).All cases recovered with good healing of fracture.According to Maryland score,the results were excellent in 14 feet,good in 7 feet,fair in 2 feet,and poor in 1 foot.The excellent and good rate was 87.5％.Conclusions By using the method of internal fixation with plastic calcaneus titanium plate,fracture site can be well exposed,which is helpful to recover calcaneus to its normal length,width,height,Gissane angle and Bohler angle.A reliable internal fixation is helpful for early stage functional excise after surgery,which can maximize the recovery of the ankle function.

Three-dimensional conformal radiotherapy combined with low-dose cisplatin chemotherapy for mid-advanced esophageal cancer / 肿瘤研究与临床

Objective To evaluate the therapeutic effectiveness and toxicity of low-dose cisplatin chemotherapy combined with three-dimensional conformal radiotherapy for mid-advanced esophageal cancer.Methods 89 patients with advanced esophageal cancer either who were inoperable or refused operation were randomized into two groups: 45 cases in the study group and 44 cases in the compared group. The study group

Development of vacuumizing system for X-ray machine head / 医疗卫生装备

This paper introduces a kind of vacuumizing system for X-ray machine head.The system function,structural composition and operation principle are expounded.It has such advantages as small empty volume,high vacuumizing speed,simple and convenient structure,etc.It shows high military,social and economic benefit because of its good maneuverability in timely and efficient maintenance on the spot.According to the feedback from maintenance department of field and local medical equipment,it is stable and reliable in working,easy to be operated and worthy of being popularized.