Objective:To explore the effect of prostaglandin E2 (PGE2) on the expression of high mobility group box-1 protein (HMGB1) in peritoneal macrophages of septic mice and its possible mechanisms.Methods:Ihe mouse peritoneal macrophages were isolated and cultured by conventional methods.The model of inflammation was established by using lipopolysaccharide (LPS) to incubate with mouse peritoneal macrophages.The PGE2,prostaglandin E receptor (EP) 4 agonist,EP4 RNAi,and DN.CREB inhibitory plasmid were used to interfere with the LPS-treated mouse peritoneal macrophage.The levels of HMGB 1 was determined by Western blot.Results:Compared with LPS alone treatment,the expression of HMGB 1 in peritoneal macrophages was increased obviously after 24 h by treatment with PGE2 and LPS,and it was also increased after the combined treatment of EP4 receptor agonist with LPS for 24 h (both P<0.05);compared with the PGE2+LPS treatment,the level of HMGB1 was decreased after knockdown of EP4 receptor expression (P<0.05);compared with EP4 receptor agonist +LPS treatment,there was no difference in HMGB1 levels in mice after the treatment with DN.CREB plasmid to suppress CREB function (P>0.05);compared with LPS alone treatment,the combined treatment of EP4 receptor agonist with LPS for 24 h could up-regulate the phosphorylation of epidermal growth factor receptor (EGFR) and protein kinase B (Akt) thr308 (P<0.05),which were blocked by EGFR inhibitor.Once Akt specific inhibitor was used before EP4 and LPS treatment,the expression of HMGB1 was declined (P<0.05).Conclusion:PGE2 can up-regulate the expression of HMGB1 in sepsis of peritoneal macrophages through EP4 receptor,which may be related to the activation of EGFR/PI3K/Akt signaling pathway.

To screen the harmful substance 5-hydroxymethyl furfural content in commercially available traditional Chinese medicine injection which are commonly used, and to preliminarily evaluate the quality of these injections, 5-hydroxymethyl furfural was taken as an index. The contents of 5-hydroxymethyl furfural in 56 samples which consist of 23 kinds of traditional Chinese medicine injections and glucose injection were determined using LC-MS/MS, and 5-hydroxymethyl furfural was detected in 52 of these samples. The minimal content was 0.0038 microg x L(-1) and the maximum content was 1420 microg x mL(-1). The contents of 5-hydroxymethyl furfural were significantly different in traditional Chinese medicine injection which came from different kinds, manufacturers or batches. The results showed the quality difference of commercially available traditional Chinese medicine injection is significant taking 5-hydroxymethyl furfural content as assessment index. More attention should be paid to the safety of 5-hydroxymethyl furfural in traditional Chinese medicine injection, and unified limitation standard should be set to improve medication safety of traditional Chinese medicine injection.

BACKGROUND:The temporal and spatial expression of fibroblast growth factor receptors 1 and 2 remains a controversial issue during kidney development,so the relationship between them and kidney development remains unclear. OBJECTIVE:To observe the dynamic expression of fibroblast growth factor receptors 1 and 2 during kidney development of mice,and to investigate the relationship between them and kidney development. METHODS:The kidneys of fetal mice[embryotic days(E)12,14,16,and 18]and neonatal mice[neonatal days(N)1,3,7,14,24,and 40]were selected to examine the temporal and spatial expression of fibroblast growth factor receptors 1 and 2 by immunohistochemistry method in kidney tissues,and quantitative analysis was performed using western blot assay. RESULTS AND CONCLUSION:(1)Immunohistochemistry showed that fibroblast growth factor receptor 1 was mainly localized in metanephric tissue surrounding the tip of the ureteral bud at E12.Subsequently,fibroblast growth factor receptor 1 was expressed in immature renal corpuscles at various stages,some distal convoluted tubules and capillary loops.The positive site was mainly concentrated in the generative region.Fibroblast growth factor receptor 2 was initially expressed in both ureteral buds and metanephric tissue.Fibroblast growth factor receptor 2 was localized in immature renal corpuscles,distal tubules,collecting ducts and thin segments of medullary loops with kidney development.However,the expression of renal corpuscles was weak.(2)Stereology and western blot assay showed that the expression of fibroblast growth factor receptor 1 was high before birth and gradually decreased after birth,while the expression was very low after N7 day.The expression level of fibroblast growth factor receptor 2 increased gradually with the kidney development and tended to be stable after N7 day.(3)The results exhibit that fibroblast growth factor receptors 1 and 2 are expressed spatially and temporally during kidney development.It is speculated that fibroblast growth factor receptors 1 and 2 may influence nephron development and maturation,and fibroblast growth factor receptor 2 is critical during the formation of ureteral buds and morphology.

Objective:To develop an automated landmark location system applicable to the case of landmark missing.Methods:Four and eighty-one lateral cephalograms, which contained 240 males and 241 females, with an average age of (24.5±5.6) years, taken from January 2015 to January 2021 in the Department of Orthodontics, Capital Medical University School of Stomatology, and met the inclusion criteria were collected. Five postgraduate orthodontic students were the annotators to manually locate 61 possible landmarks in 481 lateral cephalograms. Two assistant professors in the department as reviewers performed calibration. Two professors as arbitrators, made final decision. Data sets were established (341 were used as training set, 40 as validation set, and 100 as test set). In this paper, an automatic landmarks identification and location model based on convolutional neural networks (CNN), CephaNET, was developed. The model was trained by feeding the original image into the feature extraction module and convolutional pose machine (CPM) module to locate landmarks with high accuracy using deep supervision. Training set was enhanced to 1 684 images by histogram equalization, cropping, and adjustment of brightness. The model was trained to compare the Gaussian heat maps output from the network with the set threshold to identify landmark missing cases. Test set of 100 lateral cephalograms was used to test the accuracy of the model. The evaluation criteria used were success detection rate of missing landmark, mean radial error (MRE) and success detection rate (SDR) in the range of 2.0, 2.5, 3.0, 3.5 and 4.0 mm.Results:The model identified and located 61 commonly used landmarks in 0.13 seconds on average. It had an average accuracy of 93.5% in identifying missing landmarks. The MRE of our testing set was (1.19±0.91) mm. SDR of 2.0, 2.5, 3.0, 3.5 and 4.0 mm were 85.4%, 90.2%, 93.5%, 95.4%, 97.0% respectively.Conclusions:The model proposed in this paper could adapt to the absence of landmark in lateral cephalograms and locate 61 commonly used landmarks with high accuracy to meet the requirements of different cephalometric analysis methods.

Filamentous fungi are one of the platforms for producing fermented products. The specific characteristic of their submerged fermentation is the aggregation of mycelia that is affected by environmental conditions, leading to significantly different rheology for fermentation broth. Such a rheological change not only affects the transfer of mass, heat and momentum, but also the biosynthesis of target products and the efficiency of their production. In this article, strategies for morphological regulation of filamentous fungi are reviewed, and the impact of calcium signal transduction and chitin biosynthesis on apical growth of hyphae and branching of mycelia for their aggregation are further commented.
Fermentation ; Fungi ; physiology ; Hot Temperature ; Mycelium ; metabolism ; Rheology

Objective:To evaluate the efficacy and safety of discriminative application of Chinese patent medicines in female patients after percutaneous coronary intervention (PCI) due to acute coronary syndrome (ACS).Methods:The study population was from the Chinese Patent Medicine (CPM) trial. CPM trial was a multicenter prospective cohort study, which enrolled patients from 40 centers in mainland China between February 2012 and December 2015, with the discriminative use of Chinese patent medicines as the exposure factor. Female patients with ACS after PCI who completed 36-month follow-up were included in this analysis, and were divided into a conventional treatment group (using conventional western medicine recommended by the guidelines) and a group with the discriminative use of proprietary Chinese medicines (on the basis of conventional western medicine treatment, discriminative use of Qishen Yiqi dropping pills for Qi deficiency and blood stasis syndrome, Guanxin Danshen dropping pills for blood stasis syndrome, and Danlou tablets for phlegm and blood stasis syndrome combined with the conventional western medicine). The primary endpoint event was a composite endpoint event including cardiovascular death, nonfatal myocardial infarction, and emergency revascularization surgery. Secondary endpoint events were composite endpoint events including readmission for ACS, heart failure, stroke, and other thrombotic events. Adverse events were collected. Cox proportional risk model was used to assess the effect of discriminatory application of Chinese patent medicine on endpoint events, and sensitivity analysis was performed by comparing the results with propensity score matching analysis.Results:A total of 748 female ACS post-PCI patients were included in the analysis, aged (63.2±8.3) years. There were 370 patients in the group of discriminative application of Chinese patent medicines and 378 patients in the conventional treatment group. There were 37 cases (10.0%) and 58 cases (15.3%) of primary endpoint events in the discriminatory application of Chinese patent medicines group and the conventional treatment group, respectively. Cox analysis showed that the risk of primary endpoint in the discriminatory application of Chinese patent medicines group was lower than that in the conventional treatment group after adjusting for confounding factors (adjusted HR=0.62, 95% CI 0.40-0.96, P=0.031). There were 38 (10.3%) and 57 (15.1%) cases of secondary endpoint events in the two groups, respectively. Cox regression analysis showed that the risk of secondary endpoint events in the discriminatory application of Chinese patent medicine group was lower than that in the conventional treatment group after adjusting for confounders (adjusted HR=0.56, 95% CI 0.37-0.87, P=0.001). The results of propensity score matching analysis also showed that Chinese patent medicines based on discriminatory application could reduce the risk of primary endpoint ( HR=0.62,95% CI 0.40-0.97 ,P=0.033) and second endpoint ( HR=0.56, 95% CI 0.37-0.87, P=0.009) significantly. There was no significant difference in adverse events between the two groups (12.4% (46/370) vs. 10.3% (39/378), P=0.362). Conclusion:On the basis of conventional western medicine treatment, discriminatory application of Chinese patent medicines can reduce the risk of endpoints in female patients after PCI due to ACS without significant adverse effects.

ObjectiveTo investigate the effect of Dendrobium officinale polysaccharide （DOP）on CCl₄-induced hepatic fibrosis（HF）and its mechanism. MethodsA total of 56 male SD rats were randomly divided into seven groups： normal group（NG），model group（MG），colchicine group（CG， 0.1 mg/kg）， Fuzheng Huayu group（FG， 0.45 g/kg），low-dose DOP group（LDG， 0.05 g/kg），middle-dose DOP group（MDG， 0.1 g/kg）and high-dose DOP group（HDG，0.2 g/kg），with 8 rats in each group. HF rat model was established by subcutaneous injection with 40% CCl₄ olive oil mixture， every 3-day for 10 weeks. At the end of the sixth week， the drug groups were treated with colchicine， Fuzheng Huayu and DOP solution by gavage respectively， once a day for 4 weeks. NG and MG groups were similarly handled with an equal amount of 0.9 % normal saline. Liver histopathology was detected using hematoxylin-eosin （HE）， Masson and Sirius red staining； blood biochemistry was tested for liver function and four indicators of HF； RT-qPCR and Western Blot were used to measure the expression of α-SMA， Col-I， E-cadherin， and ZEB1 genes and proteins in the liver tissues of rats， respectively. ResultsHE， Masson， and Sirius red staining showed that the liver tissue of MG rats had typical pathologic features of HF， and the degree of HF was alleviated in LDG， MDG， and HDG rats， respectively. Liver function test results showed that the serum AST， TBIL， and AKP levels were significantly lower in LDG， MDG， and HDG， compared with those of the MG （P < 0.05 or < 0.01）. Meanwhile， ALT levels in serum deceased remarkably except in LDG （P < 0.05 or < 0.01）. The four results of HF showed that the serum HA， LN， PC-Ⅲ， and COL-Ⅳ levels in LDG， MDG， and HDG rats were significantly decreased compared with those of the MG （P < 0.05 or < 0.01）. The relative expressions of α-SMA， COL-I， and ZEB1 genes and proteins were significantly decreased in the liver tissues of LDG， MDG， and HDG （P < 0.05 or < 0.01）， and the relative expression of E-cadherin gene and protein increased （P < 0.05 or < 0.01）. In addition， the expressions of HA， α-SMA， COL-I， ZEB1 and E-cadherin were dependent on the dose of DOP. ConclusionDOP alleviated the degree of CCl₄ induced HF in rats by inhibiting the epithelial-mesenchymal transition in liver tissue.

Objective:To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT).Methods:A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ 2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results:A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment.Conclusion:ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.

Background Under the background of global climate change, temperature has increased dramatically. Most studies about association between temperature and human health are conducted in low-altitude areas, but rarely focus on plateau areas. Objective To examine the association between temperature and non-accidental mortality risk in Tibet Plateau, China and to identify vulnerable populations for formulating targeted policies of climate change adaptation. Methods The mortality data, meteorological data, and pollutant data of Tibet area between 2013 to 2019 were collected. Based on time-stratified case-crossover design, conditional logistic regression models were used to analyze the exposure-response relationship between temperature and cause-specific mortality, which was linearized to obtain excess risk for 1 ℃ change; attributable fraction was calculated for assessing burden attributable to temperature; and stratified analyses were further conducted by gender, age (＜65 years old, ≥65 years old), and causes of death (cardiovascular diseases, cerebrovascular diseases, and respiratory diseases). Sensitivity analyses were conducted by adjusting model parameters and variables. Results A total of 26 045 non-accidental deaths were collected in Tibet during 2013 and 2019, and the P₅₀ of temperature was 5.0 ℃. The non-accidental mortality risk increased as temperature become colder. A 1 ℃ decrease in temperature was associated with a 2.01% (95%CI: 0.94%-3.07%) increase in total non-accidental mortality, while the association changed to 2.05% (95%CI: 0.62%-3.47%) for male and 1.96% (95%CI: 0.34%-3.56%) for female, both of statistial significance; 1.45% (95%CI: −0.10%-2.98%) for the people <65 years old (not of significance) and 2.52% (95% CI : 1.04%-3.99%) for the people ≥65 years old (of significance); the excess risk for cardiovascular mortality was 2.65% (95%CI: 1.03%-4.24%), for cerebrovascular mortality was 3.70% (95%CI: 0.74%-6.57%), both of statistical significance, and for respiratory mortality was 2.18% (95%CI: −0.14%-4.44%), without significance. The total attribution number of non-accidental mortality was 5340 (95%CI: 2719-7528), and the total attributable fraction was 20.50% (95%CI: 10.44%-28.91%). The attributable fractions were higher in specific subgroups like male (20.72%), people ≥65 years (23.33%), and people with cardiovascular diseases (26.07%). Conclusion The exposure-response relationship between temperature and non-accidental mortality in Tibet showes that the non-accidental mortality risk increase as temperature become colder. The attributable burden of disease is heavy. Residents being male, ≥65 years, with cardiovascular diseases and respiratory diseases may be vulnerable to nonoptimal temperature.