Panax notoginseng saponin relieving the inflammatory pain caused by complete Freund’s adjuvant by inhibiting the activation of astrocytes in mice / 解剖学报

Objective To analyse the analgesic effect and possible mechanism of panax notoginseng saponin (PNS) on mouse models of chronic inflammatory pain caused by complete Freund’s adjuvant (CFA). Methods A total of 48 male C57BL/ 6J mice were divided randomly into four groups: normal saline control group (Ctrl), CFA group (CFA), CFA + PNS group (CFA+PNS), CFA + dexamethasone (DEX) group (CFA+DEX). Von Frey filaments were used to detect mechanical pain in mice. Immunohistochemistry was used to detect the number and morphological changes of glial fibrillary acidic protein (GFAP) positive astrocytes. Western blotting was used to detect the expressions of GFAP, nucleotide-binding and oligomerization domain(NOD)-like receptor thermal protein domain associated protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), Caspase-1, interleukin (IL)-1β, and IL-18 in mice’s spinal cord segments in each group. Results Compared with the Ctrl group, mice in the CFA group showed a significant decrease in mechanical pain thresholds at day 1, day 3, day 5, day 7, and day 14. Additionally, there was a significant decrease in NLRP3, ASC, Caspase-1, IL-1β and IL-18 in the spinal cord of the mice. PNS intervention could relieve mechanical pain and down-regulate the expressions of NLRP3, ASC, Caspase-1, IL-1β and IL-18 in the spinal cord of mice, with no significant difference compared with the CFA+DEX group. CFA group mice had significantly more GFAP positive cells in their posterior horns than Ctrl group mice, as measured by immunohistochemistry; PNS intervention decreased the number of GFAP positive cells in the posterior horn of the spinal cord in model mice;DEX had no effect on the number of GFAP positive cells in the dorsal horn of spinal cord. According to Western blotting results, GFAP expression in the spinal cord of the CFA group was significantly more than that of the Ctrl group; PNS intervention significantly reduced GFAP expression in the spinal cord of CFA group mice;DEX had no effect on the expression of GFAP in the posterior horn of spinal cord. Conclusion PNS has a good alleviating effect on inflammatory pain, and its mechanism may be related to inhibition of astrocyte activation and NLRP3 inflammasome activation.

Research progress in clinical application and pharmacological effect of Yiyi Fuzi Baijiang Powder / 中国中药杂志

Yiyi Fuzi Baijiang Powder(YFBP), originating from Synopsis of the Golden Chamber, is a classic prescription composed of Coicis Semen, Aconiti Lateralis Radix Praeparata, and Patriniae Herba for the treatment of abscesses and pus discharge. This article presented a systematic analysis of the clinical application of YFBP, including the indicated diseases, the number of cases, efficacy, dosage, administration methods, and compatibility with other drugs. The analysis reveals that YFBP has a wide range of clinical applications. It is commonly used, often with modifications or in combination with western medicine, for diseases in the fields of gastroente-rology, gynecology, urology, dermatology, and others. And most of the Traditional Chinese Medicine(TCM) evidence involved in these diseases are damp-heat evudence. The prescription shows rich variations in clinical administration methods, and most of which are the treatment of aqueous decoction of it. The therapeutic effect is also significant, and the total effective rate of clinical treatment is re-latively high. Additionally, this article summarized the pharmacological research on YFBP and found that it possessed various pharmacological effects, including anti-inflammatory, antioxidant, anticancer, and immune-modulating properties. Finally, correlation analysis was conducted on the main diseases, TCM types, prescription doses, pharmacological effects and action targets of YFBP, which to show the relationship between these five aspects in a visual form, reflecting the relationship between its clinical application and modern pharmacological effects. These findings provide a reference basis for further development and research on YFBP.

Reform and Practice of Ideological and Political Education of Core Courses of Biopharmaceutical Specialty———Taking The Course of Biotechnology Pharmacy as An Example / 中国生物化学与分子生物学报

As mentioned in this paper, the curriculum team of biotechnological pharmaceutics in Binzhou University reoriented the curriculum objective based on the educational policy: fostering virtue through education and consolidating fundamental spirit and soul. Additionally, the team drew on cutting-edge scientific and technological developments, social hotspots, national spirit, innovative thinking, dedication spirit and other elements, conducted in-depth study on the ideological and political elements of the subject and organically integrated them with the contents such as genetic engineering, cellular engineering, fermentation engineering, enzyme engineering, protein engineering, and established online and offline ideological and political database. Furthermore, with the aid of teaching apps like ‘Rain Classroom’, the teaching models include lecture, case-based teaching, group discussion, and blended teaching for the subject. In the meantime, the ideological and political educational requirements were integrated into the curriculum evaluation system. Taking the genetic engineering pharmaceutics as an example, reform and practice for the ideological and political education for the undergraduate subject, biotechnological pharmaceutics, was applied. This paper expatiated the teaching practice of the ideological and political education, and reviewed the outcomes of the curriculum reform over these years in an effort to formulate a set of all-round programs for the reform and practice of the ideological and political education that can be replicated and improved continuously. This paper aims not only in developing high-caliber biomedical talents with a strong sense of patriotism and social responsibility, but also in providing a reference for the teaching reform of related subjects.

Effects of astragalus polysaccharides on improvement of liver and kidney injury and regulation of intestinal flora structure in cadmium-exposed rats / 中国药理学通报

Aim To investigate the effects of astragalus polysaccharides on the improvement of liver and kidney injury and the regulation of intestinal flora structure in cadmium exposed rats. Methods Rats exposed to cadmium were established by intraperitoneal injection of CdCl2. After continuous intragastric administration of astragalus polysaccharides for five weeks, urine, liver, kidney and feces were collected. The cadmium residues in urine, liver and kidney were detected by Graphite Furnace Atomic absorption spectrometry, the pathological changes of liver and kidney were observed by HE staining, and Illumina PE250 sequencing and bioinformatics software were used to analyze the structure of intestinal flora. Results After intraperitoneal injection of CdCl2, the accumulation of cadmium in urine, liver and kidney increased significantly, some liver and kidney cells showed pathological damage such as swelling, necrosis and inflammatory cell infiltration. Chao, ace and shannon indexes decreased significantly, while simpson index increased significantly. The number of OTU decreased. And the abundance of Ruminococcus, Bacteroides, Flavonifractor, Roseburia and Elusmicrobium decreased significantly, but Lactobacillus, that of Lachnospiracea_incertae_sedis, Parasutterella, Clostridium XlVb, Clostridium XI, Integinimonas and Fusobacterium increased significantly. Compared with the normal control group, the differences was statistically significant(P<0.05 or P<0.01). After intragastric administration of astragalus polysaccharides, cadmium accumulation in urine, liver and kidney decreased significantly, liver and kidney cell damage alleviated, and inflammatory cell infiltration reduced. Chao, ace and shannon index increased markedly, and simpson index decreased significantly. OTU number increased. And the bundance of Prevotella, Bacteroides, Parasutterella, Elismicrobium and Barnesiella raised significantly, that of Ruminococcus, Oscillibacter, Flavonifractor, Clostridium XlVa, Roseburia, Lactobacillus, Ruminococcus2, Lachnospiracea_incertae_sedis, Clostridium IV, Clostridium XlVb, Clostridium XI and integinimonas decreased significantly, which was statistically significant compared with the group exposed to cadmium alone(P<0.05 or P<0.01). Conclusions Astragalus polysaccharides may improve liver and kidney injury by reducing cadmium accumulation and regulating the structure of intestinal flora in cadmium exposed rats.

Effect of different courses of Budesonide on endoscopic dacryocystorhinostomy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To compare the effect of different courses of budesonide nasal spray on the postoperative efficacy of endoscopic dacryocystorhinostomy.METHOD: Prospective study. A total of 90 patients(90 eyes)with chronic dacryocystitis who underwent endoscopic dacryocystorhinostomy in our hospital from January 2019 to April 2022 were selected, and they were randomly divided into three groups. In group A, 30 patients(30 eyes)continued to use budesonide nasal spray for 2mo after surgery; in group B, 30 patients(30 eyes)continued to use budesonide nasal spray for 3mo after surgery; in group C, 30 patients(30 eyes)continued to use budesonide nasal spray for 4mo after surgery. Follow-up for 6mo after surgery, Lund-Kenndey score, surgical efficacy and complications of the three groups were compared.RESULT: At 3, 4 and 6mo after surgery, the Lund-Kenndey score of group C was lower than that of group A(P&#x003C;0.05), and there was no statistical difference between group C and group B(P&#x003E;0.05). Following up to 6mo, the surgical efficacy of group C was better than that of group A, and the incidence of complications was lower than that of group A(P&#x003C;0.05); There was no statistically significant difference in efficacy and complications between group C and group B(P&#x003E;0.05).CONCLUSION: Budesonide combined with endoscopic dacryocystorhinostomy has acceptable efficacy in the treatment of chronic dacryocystitis. After 3mo of treatment, inflammation can be well controlled, which can reduce the occurrence of postoperative complications and improve the effective rate of surgery. However, increasing the treatment course cannot further improve the effective rate of surgery.

The role of phosphatidylcholine 34:1 in the occurrence, development and treatment of ulcerative colitis

Lipid homeostasis is considered to be related to intestinal metabolic balance, while its role in the pathogenesis and treatment of ulcerative colitis (UC) remains largely unexplored. The present study aimed to identify the target lipids related to the occurrence, development and treatment of UC by comparing the lipidomics of UC patients, mice and colonic organoids with the corresponding healthy controls. Here, multi-dimensional lipidomics based on LC-QTOF/MS, LC-MS/MS and iMScope systems were constructed and used to decipher the alteration of lipidomic profiles. The results indicated that UC patients and mice were often accompanied by dysregulation of lipid homeostasis, in which triglycerides and phosphatidylcholines were significantly reduced. Notably, phosphatidylcholine 34:1 (PC34:1) was characterized by high abundance and closely correlation with UC disease. Our results also revealed that down-regulation of PC synthase PCYT1α and Pemt caused by UC modeling was the main factor leading to the reduction of PC34:1, and exogenous PC34:1 could greatly enhance the fumarate level via inhibiting the transformation of glutamate to N-acetylglutamate, thus exerting an anti-UC effect. Collectively, our study not only supplies common technologies and strategies for exploring lipid metabolism in mammals, but also provides opportunities for the discovery of therapeutic agents and biomarkers of UC.

Hepatoprotective activity of Zha Xun and its different solvent-eluting components / 药学学报

A pharmacophore-based study was conducted to investigate the therapeutic activity of the traditional Tibetan medicine Zha Xun (ZX) in liver diseases. In the present study, the protective effect of ZX on the acute liver injury induced by concanavalin A (ConA) and 0.15% carbon tetrachloride (0.15% CCl4) in ICR mice was evaluated, and the results showed that ZX significantly reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the ConA-induced acute immune liver injury model and the CCl4-induced acute oxidative liver injury model (P < 0.05). Subsequently, the protective effects of aqueous, 95% ethanol, 60% ethanol and 30% ethanol eluting fractions of ZX, and fulvic acid, the main water-soluble constituent of ZX, were evaluated against acute oxidative liver injury induced by 0.15% CCl4 in mice. The results showed that different solvent-eluting fractions of ZX showed certain hepatoprotective activities, among which the aqueous extract of ZX and 30% ethanol extract of ZX significantly reduced the serum levels of ALT, AST, and lactate dehydrogenase (LDH) in mice (P < 0.05), and the serum levels of LDH in mice were significantly reduced by fulvic acid (P < 0.05), which showed significant hepatoprotective activity. The protective activities and preliminary mechanisms of the total extract of ZX, the aqueous extract of ZX, the 30% ethanol extract of ZX, and fulvic acid against hepatocellular injury in vitro were further evaluated by using the H2O2-induced hepatocellular injury model. The results showed that the components could significantly inhibit H2O2-induced hepatocellular injury, reduce the levels of ALT, alkaline phosphatase (ALP), and LDH, improve the survival rate of hepatocellular cells, and reduce the content of intracellular reactive oxygen species (ROS) in cell culture. At the same time, it can inhibit hepatocyte apoptosis by increasing the expression ratio of Bcl-2/BAX protein and decreasing the expression ratio of cleaved caspase-3/pro caspase-3 protein. The present study showed that ZX has clear hepatoprotective activity in vitro and in vivo, and the different solvent elution fractions of ZX showed certain hepatoprotective activity, among which the aqueous extract of ZX, 30% ethanol extract of ZX had better hepatoprotective activity, and the activity of 60% ethanol extract of ZX was stronger than that of 95% ethanol extract of ZX. The activity of ZX and its water-soluble elution site exerted hepatoprotective effects by inhibiting hepatocyte apoptosis and oxidative stress. The animals used in this experiment and related disposal meet the requirements of animal welfare, and have been reviewed and approved by the Laboratory Animal Management and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences (approval number: 00004018).

Rapid identification of components in Wuzhuyu Decoction using UHPLC Q-Exactive Orbitrap MS~n and molecular network technology / 中国中药杂志

Wuzhuyu Decoction, the classical formula recorded in the Treatise on Febrile Diseases(Shang Han Lun), has been included in the Catalogue of Ancient Classic Prescriptions(the First Batch). Consisting of Euodiae Fructus, Ginseng Radix et Rhizoma, Zingiberis Rhizoma Recens, and Jujubae Fructus, it is effective in warming the middle, tonifying deficiency, dispelling cold, and descending adverse Qi, and is widely applied clinically with remarkable efficacies. For a classical formula, the chemical composition is the material basis and an important premise for quantity value transfer. This study aimed to establish a rapid identification method of chemical components in Wuzhuyu Decoction by high-resolution mass spectrometry(HR-MS) and molecular network. AQUITY UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 μm) was used for sample separation, and acetonitrile-0.1% formic acid in water was used as mobile phases for gradient elution. Q-Exactive Orbitrap MS data were collected in positive and negative ion modes, and GNPS molecular network was plotted according to the similarity of MS/MS fragmentation modes. Cytoscape 3.6.1 was used to screen molecular clusters with similar structures. Finally, the chemical components of Wuzhuyu Decoction were rapidly identified according to the controls, as well as the information of retention time, accurate relative molecular weight of HR-MS, and MS/MS multistage fragments. A total of 105 chemical components were identified in Wuzhuyu Decoction. This study can provide data for the follow-up quality control, standard substance research, and pharmacodynamic material research on Wuzhuyu Decoction, as well as references for the rapid qualitative analysis of the chemical components of Chinese medicine.

A nomogram for preoperative prediction of lymph node metastasis in patients with intrahepatic cholangiocarcinoma based on inflammation-related markers / 中华外科杂志

Objectives: To construct a nomogram for prediction of intrahepatic cholangiocarcinoma (ICC) lymph node metastasis based on inflammation-related markers,and to conduct its clinical verification. Methods: Clinical and pathological data of 858 ICC patients who underwent radical resection were retrospectively collected at 10 domestic tertiary hospitals in China from January 2010 to December 2018. Among the 508 patients who underwent lymph node dissection,207 cases had complete variable clinical data for constructing the nomogram,including 84 males,123 females,109 patients≥60 years old,98 patients<60 years old and 69 patients were pathologically diagnosed with positive lymph nodes after surgery. Receiver operating characteristic curve was drawn to calculate the accuracy of preoperative imaging examinations to determine lymph node status,and the difference in overall survival time was compared by Log-rank test. Partial regression squares and statistically significant preoperative variables were screened by backward stepwise regression analysis. R software was applied to construct a nomogram,clinical decision curve and clinical influence curve,and Bootstrap method was used for internal verification. Moreover,retrospectively collecting clinical information of 107 ICC patients with intraoperative lymph node dissection admitted to 9 tertiary hospitals in China from January 2019 to June 2021 was for external verification to verify the accuracy of the nomogram. 80 patients with complete clinical data but without lymph node dissection were divided into lymph node metastasis high-risk group and low-risk group according to the score of the nomogram among the 858 patients. Log-rank test was used to compare the overall survival of patients with or without lymph node metastasis diagnosed by pathology. Results: The area under the curve of preoperative imaging examinations for lymph node status assessment of 440 patients was 0.615,with a false negative rate of 62.8% (113/180) and a false positive rate of 14.2% (37/260). The median survival time of 207 patients used to construct a nomogram with positive or negative postoperative pathological lymph node metastases was 18.5 months and 27.1 months,respectively (P<0.05). Five variables related to lymph node metastasis were screened out by backward stepwise regression analysis,which were combined calculi,neutrophil/lymphocyte ratio,albumin,liver capsule invasion and systemic immune inflammation index,according to which a nomogram was constructed with concordance index(C-index) of 0.737 (95%CI: 0.667 to 0.806). The C-index of external verification was 0.674 (95%CI:0.569 to 0.779). The calibration prediction curve was in good agreement with the reference curve. The results of the clinical decision curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.32,the maximum net benefit could be obtained by 0.11,and the cost/benefit ratio was 1∶2. The results of clinical influence curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.6,the probability of correctly predicting lymph node metastasis could reach more than 90%. There was no significant difference in overall survival time between patients with high/low risk of lymph node metastasis assessed by the nomogram and those with pathologically confirmed lymph node metastasis or without lymph node metastasis (Log-rank test:P=0.082 and 0.510,respectively). Conclusion: The prediction accuracy of preoperative nomogram for ICC lymph node metastasis based on inflammation-related markers is satisfactory,which can be used as a supplementary method for preoperative diagnosis of lymph node metastasis and is helpful for clinicians to make personalized decision of lymph node dissection for patients with ICC.

Survival analysis of patients with intrahepatic cholangiocarcinoma treated with adjuvant chemotherapy after radical resection based on CoxPH model and deep learning algorithm / 中华外科杂志

Objective: To establish a predictive model for survival benefit of patients with intrahepatic cholangiocarcinoma (ICC) who received adjuvant chemotherapy after radical resection. Methods: The clinical and pathological data of 249 patients with ICC who underwent radical resection and adjuvant chemotherapy at 8 hospitals in China from January 2010 to December 2018 were retrospectively collected. There were 121 males and 128 females,with 88 cases>60 years old and 161 cases≤60 years old. Feature selection was performed by univariate and multivariate Cox regression analysis. Overall survival time and survival status were used as outcome indicators,then target clinical features were selected. Patients were stratified into high-risk group and low-risk group,survival differences between the two groups were analyzed. Using the selected clinical features, the traditional CoxPH model and deep learning DeepSurv survival prediction model were constructed, and the performance of the models were evaluated according to concordance index(C-index). Results: Portal vein invasion, carcinoembryonic antigen>5 μg/L,abnormal lymphocyte count, low grade tumor pathological differentiation and positive lymph nodes>0 were independent adverse prognostic factors for overall survival in 249 patients with adjuvant chemotherapy after radical resection (all P<0.05). The survival benefit of adjuvant chemotherapy in the high-risk group was significantly lower than that in the low-risk group (P<0.05). Using the above five features, the traditional CoxPH model and the deep learning DeepSurv survival prediction model were constructed. The C-index values of the training set were 0.687 and 0.770, and the C-index values of the test set were 0.606 and 0.763,respectively. Conclusion: Compared with the traditional Cox model, the DeepSurv model can more accurately predict the survival probability of patients with ICC undergoing adjuvant chemotherapy at a certain time point, and more accurately judge the survival benefit of adjuvant chemotherapy.

Exploring the significance of chemotherapy in the perioperative application of biliary tract carcinomas / 中华外科杂志

Biliary tract cancer is extremely malignant with a poor prognosis. At the moment, the only curative method available is radical resection. Targeted and immunotherapy are currently advancing quickly, but chemotherapy still holds a key role in the perioperative management of biliary cancer. Perioperative chemotherapy aims to decrease tumor volume before surgery so that patients can have their tumors surgically removed or have a higher radical resection rate. It also aims to remove any tumor cells that remain after surgery and prevent the growth of new tumors. Chemotherapy-based combination treatment techniques have been increasingly investigated in recent years to improve perioperative care and patient survival. From the standpoint of chemotherapy regimens and clinical trial success in the perioperative phase of radical surgery, the value of chemotherapy in the perioperative period of biliary tract cancer were explored in this paper.

Impact of individual and combined assessment of age- and sex-specific brachial-ankle pulse wave velocity and pulse pressure on all-cause mortality / 中华心血管病杂志

Objective: To evaluate the impact of individual and combined assessment of age- and sex-specific brachial-ankle pulse wave velocity (baPWV) and pulse pressure (PP) on all-cause mortality. Methods: This study is a prospective cohort study. Individuals participated in the Kailuan Study and completed baPWV measurements between 2010 and 2016 were included in this study. After stratifying by sex, 75th percentile baPWV and PP values for different age group were calculated at five years interval. BaPWV and PP values below the 75th percentile were defined as normal, and those above or equal to the 75th percentile were defined as increased. The participants were allocated to four groups according to their PP and baPWV status: normal baPWV/PP group, high baPWV/normal PP group, normal baPWV/high PP group and high baPWV/PP group. The primary outcome was all-cause mortality during the follow-up period. Cox proportional hazards models were used to explore the impact of individual and combined assessment of baPWV and PP on all-cause mortality events. Results: A total of 39 339 participants were enrolled in this study, aged (49.3±12.8) years, of which 28 731 (73.03%) were males. There were 23 268, 6 025, 6 210 and 3 836 cases in the normal baPWV/PP group, high baPWV/normal PP group, normal baPWV/high PP group and high baPWV/PP group, respectively. The average follow-up duration was (4.98±2.53) years. During the follow-up period, all-cause mortality occurred in 998 individuals. Multivariate Cox regression analysis showed increased risk of all-cause mortality in the high baPWV/normal PP group (HR=1.27, 95%CI 1.07-1.50), and in the high baPWV/PP group (HR=1.33, 95%CI 1.08-1.65) compared to the normal baPWV/PP group. Increased pulse pressure alone had no impcat on all-cause death (HR=1.06, 95%CI 0.87-1.29). Conclusions: The risk of all-cause mortality significantly increases with increased age-and sex-specific baPWV and PP values. BaPWV may be a better predictor of all-cause mortality than PP in this cohort.

Hepatoprotective activity of cis-(trans)-emodin-emodin dianthrone from Polygonum multiflorum Thunb / 药学学报

The cis-emodin-emodin dianthrone (compound 1) and trans-emodin-emodin dianthrone (compound 2) were extracted from Polygonum multiflorum Thunb. The protective effect and mechanism of compound 1 and compound 2 (emodin-emodin dianthrones) on acute liver injury induced by concanavalin A (ConA) in ICR mice was first investigated. The results indicated that emodin-emodin dianthrones at 1 mg·kg-1 significantly reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level (P < 0.05). Emodin-emodin dianthrones also improved liver histopathological damage in liver-injured mice. The level of Bcl-2-associated X protein (Bax) mRNA in liver was significantly reduced by 1 mg·kg-1 of emodin-emodin dianthrones, while the level of B-cell lymphoma-2 (Bcl-2) mRNA expression was significantly increased (P < 0.05). The protective activity of compounds 1 and 2 against hepatocyte injury was further evaluated by hydrogen peroxide (H2O2)-induced hepatocyte injury. Compounds 1 and 2 significantly inhibited H2O2-induced hepatocyte injury and reduced the levels of ALT, AST, alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) in cell culture. Compounds 1 and 2 also significantly improved the cell survival rate and decreased H2O2-induced oxidative stress in hepatocytes. Compound 1 (0.5 µmol·L-1) significantly increased the enzymatic activity of superoxide dismutase (SOD) in hepatocytes (P < 0.01), and 0.5 µmol·L-1 of compound 2 significantly decreased the intracellular reactive oxygen species (ROS), increased SOD enzyme activity, and glutathione (GSH) content (P < 0.01). Compounds 1 and 2 at 0.5 µmol·L-1 also inhibited hepatocyte apoptosis by increasing the protein expression ratio of Bcl-2/Bax (P < 0.05) and decreasing the protein expression ratio of cleaved caspase-3 and pro caspase-3 (P < 0.05). This study indicates that the emodin-emodin dianthrones from Polygonum multiflorum Thunb. have liver-protective activity. Compounds 1 and 2 exerted hepatoprotective effects by inhibiting apoptosis and oxidative stress. The study provides an important material basis for the hepatoprotective effect of commonly used amounts of Polygonum multiflorum Thunb.

Advances in applications of molecular dynamics simulation techniques to the research of self-assembled nano-drug delivery systems / 药学学报

Molecular dynamics simulation technology relies on Newtonian mechanics to simulate the motion of molecular system of the real system by computer simulation. It has been used in the research of self-assembly processes illustration and macroscopic performance prediction of self-assembly nano-drug delivery systems (NDDS) in recent years, which contributes to the facilitation and accurate design of preparations. In this review, the definitions, catalogues, and the modules of molecular dynamics simulation techniques are introduced, and the current status of their applications are summarized in the acquisition and analysis of microscale information, such as particle size, morphology, the formation of microdomains, and molecule distribution of the self-assembly NDDS and the prediction of their macroscale performances, including stability, drug loading capacity, drug release kinetics and transmembrane properties. Moreover, the existing applications of the molecular dynamic simulation technology in the formulation prediction of self-assembled NDDS were also summarized. It is expected that the new strategies will promote the prediction of NDDS formulation and lay a theoretical foundation for an appropriate approach in NDDS studies and a reference for the wider application of molecular dynamics simulation technology in pharmaceutics.

Intestinal Cckbr-specific knockout mouse as a novel model of salt-sensitive hypertension via sodium over-absorption / 老年心脏病学杂志（英文版）

OBJECTIVES@#To investigate the value of CCKBRfl/fl villin-Cre mice as a mouse model of salt-sensitive hypertension (SSH).@*METHODS@#In the first part, 2-month-old CCKBRfl/fl villin-Cre mice (CKO) and control CCKBRfl/fl mice (WT) were fed with normal diet (0.4% NaCl) or high salt diet (4% NaCl), separately for 6 weeks. In the rescue study, one week of hydrochlorothiazide or saline injection were treated with the CKO mice fed high salt diet. The blood pressure, biochemical indexes, and the expression of small intestinal sodium transporters (NHE3, NKCC1, eNaC) was detected. The organ injury markers (MMP2/MMP9) and the histopathological changes of kidneys were observed, whereas the changes of duodenal sodium absorption were detected by small intestinal perfusion in vivo.@*RESULTS@#The CCKBRfl/fl villin-Cre mice with high salt intake exhibited high blood pressure, increased duodenal sodium absorption and urinary sodium excretion, and with renal injury. The protein expression of NHE3, NKCC1 and eNaC were also significant increase in the intestine of CKO-HS mice. Treatment with hydrochlorothiazide remarkably attenuated the elevated blood pressure by high salt absorption in the CCKBRfl/fl villin-Cre mice, but no significant histopathological changes were observed.@*CONCLUSIONS@#These results support a crucial role of intestinal Cckbr deficiency on SSH development and the diuretic antihypertension effect in CCKBRfl/fl villin-Cre mice. The CCKBRfl/fl villin-Cre mice with the high salt intake may serve as a stable model of salt-sensitive hypertensive induced by sodium overloading.

Establishment and Clinical Significance of Prognostic Nomogram Model for Diffuse Large B-Cell Lymphoma Based on Immunohistochemistry Markers and International Prognostic Index Scores / 中国实验血液学杂志

OBJECTIVE@#To retrospectively analyze clinical characteristics and survival time of patients with diffuse large B-cell lymphoma (DLBCL), detect prognosis-related markers, and establish a nomogram prognostic model of clinical factors combined with biomarkers.@*METHODS@#One hundred and thirty-seven patients with DLBCL were included in this study from January 2014 to March 2019 in the First Affiliated Hospital of Nanchang University. The expression of GCET1, LMO2, BCL-6, BCL-2 and MYC protein were detected by immunohistochemistry (IHC), then the influences of these proteins on the survival and prognosis of the patients were analyzed. Univariate and multivariate Cox regression analysis were used to gradually screen the prognostic factors in nomogram model. Finally, nomogram model was established according to the result of multivariate analysis.@*RESULTS@#The positive expression of GCET1 protein was more common in patients with Ann Arbor staging I/II (P =0.011). Compared with negative patients, patients with positive expression of LMO2 protein did not often show B symptoms (P =0.042), and could achieve better short-term curative effect (P =0.005). The overall survival (OS) time of patients with positive expression of LMO2 protein was significantly longer than those with negative expression of LMO2 protein (P =0.018), though the expression of LMO2 protein did not correlate with progression-free survival (PFS) (P >0.05). However, the expression of GCET1 protein had no significant correlation with OS and PFS. Multivariate Cox regression analysis showed that nomogram model consisted of 5 prognostic factors, including international prognostic index (IPI), LMO2 protein, BCL-2 protein, MYC protein and rituximab. The C-index applied to the nomogram model for predicting 4-year OS rate was 0.847. Moreover, the calibrated curve of 4-year OS showed that nomogram prediction had good agreement with actual prognosis.@*CONCLUSION@#The nomogram model incorporating clinical characteristics and IHC biomarkers has good discrimination and calibration, which provides a useful tool for the risk stratification of DLBCL.

Expression and Clinical Significance of Exosome Derived MiR-181b-5p in Children with Acute Lymphoblastic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the expression level of exosome derived miR-181b-5p in different disease stages of children with acute lymphoblastic leukemia and its relationship with clinical characteristics.@*METHODS@#Bone marrow plasma samples of 86 children with ALL were collected. Exosomes were extracted by exosome extraction kit, and RNA in exosomes was extracted by TRIzol method. The levels of miR-181b-5p in the blood plasma exosomes of the patients in the newly diagnosed group, relapse group, remission group and control group were detected by qRT- PCR. The difference of miR-181b-5p expression level in each group was compared and analyzed, and the relationship between miR-181b-5p expression level and clinical characteristics was analyzed.@*RESULTS@#The expression level of exosomal miR-181b-5p in the newly diagnosed group and the relapsed group was significantly lower than that in the remission group and the control group (P< 0.05). The expression level of exosomal miR-181b-5p in T-ALL children was higher than that in B-ALL children (P<0.05). The expression level of plasma exosomal miR-181b-5p in male children was higher than that in female children (P<0.01).@*CONCLUSION@#Exosome derived miR-181b-5p changes dynamically in the course of ALL children, and can be used as a marker miRNA to monitor disease status. Exosomes can transmit information in the tumor microenvironment and serve as a potential carrier for biomolecular targeted therapy.

Inositol 1,4,5-triphosphate receptor 3 promotes renal cyst development in autosomal dominant polycystic kidney disease / 生理学报

The purpose of the present study was to determine the role of inositol 1,4,5-trisphosphate receptor 3 (IP3R3) in renal cyst development in autosomal dominant polycystic kidney disease (ADPKD). 2-aminoethoxy-diphenyl borate (2-APB) and shRNA were used to suppress the expression of IP3R3. The effect of IP3R3 on cyst growth was investigated in Madin-Darby canine kidney (MDCK) cyst model, embryonic kidney cyst model and kidney specific Pkd1 knockout (PKD) mouse model. The underlying mechanism of IP3R3 in promoting renal cyst development was investigated by Western blot and immunofluorescence staining. The results showed that the expression level of IP3R3 was significantly increased in the kidneys of PKD mice. Inhibiting IP3R3 by 2-APB or shRNA significantly retarded cyst expansion in MDCK cyst model and embryonic kidney cyst model. Western blot and immunofluorescence staining results showed that hyperactivated cAMP-PKA signaling pathway in the growth process of ADPKD cyst promoted the expression of IP3R3, which was accompanied by a subcellular redistribution process in which IP3R3 was translocated from endoplasmic reticulum to intercellular junction. The abnormal expression and subcellular localization of IP3R3 further promoted cyst epithelial cell proliferation by activating MAPK and mTOR signaling pathways and accelerating cell cycle. These results suggest that the expression and subcellular distribution of IP3R3 are involved in promoting renal cyst development, which implies IP3R3 as a potential therapeutic target of ADPKD.

Comprehensive review and prospect of acupuncture and moxibustion discipline: a review of Discipline History of Acupuncture and Moxibustion in China / 中国针灸

After reviewing and evaluating the Discipline History of Acupuncture and Moxibustion in China, the authors concludes that this book has the following characteristics: the scientific research focuses on the combination of internal and external history, and the conclusions are rigorous; the narrative style and structure featured by the division of discipline history of ancient times, modern times and current times are quite characteristic and enlightening; the reference materials are detailed and advanced, which showes profound thoughts and concerns about the difficulties and challenges faced by the development of acupuncture and moxibustion discipline and the internal path selection of acupuncture and moxibustion research. In addition, this book discusses the unique importance of the cultural attribute behind acupuncture and moxibustion technology in the process of theoretical research of acupuncture and moxibustion.

Incidence and prognosis of olfactory and gustatory dysfunctions related to infection of SARS-CoV-2 Omicron strain: a national multi-center survey of 35 566 population / 中华耳鼻咽喉头颈外科杂志

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.