1.Aromatic Substances and Their Clinical Application: A Review
Yundan GUO ; Lulu WANG ; Zhili ZHANG ; Chen GUO ; Zhihong PI ; Wei GONG ; Zongping WU ; Dayu WANG ; Tianle GAO ; Cai TIE ; Yuan LIN ; Jiandong JIANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(22):264-272
Aromatherapy refers to the method of using the aromatic components of plants in appropriate forms to act on the entire body or a specific area to prevent and treat diseases. Essential oils used in aromatherapy are hydrophobic liquids containing volatile aromatic molecules, such as limonene, linalool, linalool acetate, geraniol, and citronellol. These chemicals have been extensively studied and shown to have a variety of functions, including reducing anxiety, relieving depression, promoting sleep, and providing pain relief. Terpenoids are a class of organic molecules with relatively low lipid solubility. After being inhaled, they can pass through the nasal mucosa for transfer or penetrate the skin and enter the bloodstream upon local application. Some of these substances also have the ability to cross the blood-brain barrier, thereby exerting effects on the central nervous system. Currently, the academic community generally agrees that products such as essential oils and aromatherapy from aromatic plants have certain health benefits. However, the process of extracting a single component from it and successfully developing it into a drug still faces many challenges. Its safety and efficacy still need to be further verified through more rigorous and systematic experiments. This article systematically elaborated on the efficacy of aromatic substances, including plant extracts and natural small molecule compounds, in antibacterial and antiviral fields and the regulation of nervous system activity. As a result, a deeper understanding of aromatherapy was achieved. At the same time, the potential of these aromatic substances for drug development was thoroughly explored, providing important references and insights for possible future drug research and application.
2.Efficacy evaluation of extending or switching to tenofovir amibufenamide in patients with chronic hepatitis B: a phase Ⅲ randomized controlled study
Zhihong LIU ; Qinglong JIN ; Yuexin ZHANG ; Guozhong GONG ; Guicheng WU ; Lvfeng YAO ; Xiaofeng WEN ; Zhiliang GAO ; Yan HUANG ; Daokun YANG ; Enqiang CHEN ; Qing MAO ; Shide LIN ; Jia SHANG ; Huanyu GONG ; Lihua ZHONG ; Huafa YIN ; Fengmei WANG ; Peng HU ; Xiaoqing ZHANG ; Qunjie GAO ; Chaonan JIN ; Chuan LI ; Junqi NIU ; Jinlin HOU
Chinese Journal of Hepatology 2024;32(10):883-892
Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).
3.Safety profile of tenofovir amibufenamide therapy extension or switching in patients with chronic hepatitis B: a phase Ⅲ multicenter, randomized controlled trial
Zhihong LIU ; Qinglong JIN ; Yuexin ZHANG ; Guozhong GONG ; Guicheng WU ; Lvfeng YAO ; Xiaofeng WEN ; Zhiliang GAO ; Yan HUANG ; Daokun YANG ; Enqiang CHEN ; Qing MAO ; Shide LIN ; Jia SHANG ; Huanyu GONG ; Lihua ZHONG ; Huafa YIN ; Fengmei WANG ; Peng HU ; Xiaoqing ZHANG ; Qunjie GAO ; Peng XIA ; Chuan LI ; Junqi NIU ; Jinlin HOU
Chinese Journal of Hepatology 2024;32(10):893-903
Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated.Results:666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion:CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).
4.Effect of turmeric extract regulating Nrf2/Keap1 pathway on sepsis-induced acute lung injury in rats
Shu WANG ; Fuxing LI ; Meng WANG ; Yihua ZHOU ; Zhihong YU ; Yuanqi GONG
Chinese Journal of Immunology 2024;40(12):2580-2584,2590
Objective:To investigate effect of curcumin on sepsis-induced acute lung injury rats based on Nrf2/Keap1 signaling pathway.Methods:Thirty rats were randomly divided into sham operation group,model group,curcumin low,medium and high doses groups,with 6 rats in each group.Rats in sham operation group were exposed by removing cecum and then returned to abdominal cavity,while rest of rats were constructed a model of acute lung injury in sepsis,and drugs were administered immediately after surgery for 3 consecutive days.After anaesthesia with 40 mg/kg pentobarbital,blood and alveolar lavage fluid were collected from common carotid arteries,and lung tissues were taken after death.Severity of sepsis in rats was evaluated;total cell count and neutrophil count of alveo-lar lavage fluid were detected;HE staining was performed to observe pathological damage of lung tissues;colorimetric method was used to detect SOD and MDA activities of lung tissues;ELISA was used to detect TNF-α,IL-1β and IL-6 levels;qRT-PCR was used to detect Nrf2,Keap1 and HO-1 mRNA expressions in lung tissues;Western blot was used to detect Nrf2,Keap1 and HO-1 protein expressions in lung tissues.Results:Compared with sham operation group,severity scores of sepsis in model group,curcumin low,medium and high doses groups were increased,total number of cells and neutrophil number were increased,SOD level was decreased,MDA level was increased,TNF-α,IL-1β and IL-6 levels were increased,Nrf2,HO-1 mRNA and protein expressions were decreased,Keap1 mRNA and protein expressions were increased(P<0.05);compared with model group,sepsis severity scores of curcumin low,medium and high doses groups were decreased,total number of cells and neutrophil number were decreased,SOD level was increased,MDA level was decreased,TNF-α,IL-1β and IL-6 levels were decreased,Nrf2 and HO-1 mRNA and protein expressions were increased,Keap1 mRNA and protein expressions were decreased in a dose-dependent manner(P<0.05).Conclu-sion:Curcumin can improve acute lung injury in rats with sepsis,improve lung pathological injury and protect lung tissue,which may be achieved by regulating Nrf2/Keap1 pathway and expressions of related factors.
5.Clinicopathological and molecular genetic features of Crohn′s disease
Yuxi GONG ; Chunni CHEN ; Yefan YANG ; Shuning SUN ; Yang SHAO ; Liuqing ZHU ; Yuqian SHI ; Xiao LI ; Xue HAN ; Zhihong ZHANG
Chinese Journal of Pathology 2024;53(4):351-357
Objective:To investigate the clinicopathological and molecular genetic characteristics of Crohn′s disease (CD).Methods:A retrospective analysis was conducted on 52 CD patients who underwent surgical resection at the First Affiliated Hospital of Nanjing Medical University between January 2014 and June 2023. Clinical presentations and histopathological features were assessed. Whole-genome sequencing was performed on 17 of the samples, followed by sequencing and pathway enrichment analyses. Immunohistochemistry was used to assess the expression of frequently mutated genes.Results:Among the 52 patients, 34 were males and 18 were females, male-to-female ratio was 1.9∶1.0, with a median age of 45 years at surgery and 35 years at diagnosis. According to the Montreal classification, A3 (51.9%,27/52), B2 (61.5%, 32/52), and L3 (50.0%,26/52) subtypes were the most predominant. Abdominal pain and diarrhea were the common symptoms. Histopathological features seen in all 52 patients included transmural inflammation, disruption of cryptal architecture, lymphoplasmacytic infiltration, varying degrees of submucosal fibrosis and thickening, increased enteric nerve fibers and neuronal proliferation. Mucosal defects, fissure ulcers, abscesses, pseudopolyps, and adenomatous proliferation were also observed in 51 (98.1%), 38 (73.1%), 28 (53.8%), 45 (86.5%), and 28 (53.8%) cases, respectively. Thirty-one (59.6%) cases had non-caseating granulomas, and 3 (5.8%) cases had intestinal mucosal glandular epithelial dysplasia. Molecular analysis showed that 12/17 CD patients exhibited mutations in at least one mucin family gene (MUC2, MUC3A, MUC4, MUC6, MUC12, MUC17), and MUC4 was the most frequently mutated in 7/17 of cases. Immunohistochemical stains showed reduced MUC4 expression in epithelial cells, with increased MUC4 expression in the epithelial surface, particularly around areas of inflammatory cell aggregation; and minimal expression in the lower half of the epithelium.Conclusions:CD exhibits diverse clinical and pathological features, necessitating a comprehensive multidimensional analysis for diagnosis. Mutations and expression alterations in mucin family genes, particularly MUC4, may play crucial roles in the pathogenesis of CD.
6.Construction and validation of a predictive model for septic shock based on propensity score matching
Yang FANG ; Ying LI ; Zhihong CHEN ; Shengnan ZHENG ; Jian GONG ; Qihua WU ; Xiaoyu YANG ; Xiuping WEN ; Donghong LIN
Journal of Clinical Medicine in Practice 2024;28(21):53-59
Objective To construct a predictive model for septic shock based on the propensity score matching (PSM) method and validate its effectiveness. Methods A total of 114 patients with sepsis were enrolled as study objects, and were divided into septic shock group (40 patients) and sepsis group (74 patients) according to whether they developed septic shock. PSM was performed with a ratio of septic shock to sepsis of 1∶2, resulting in the inclusion of 30 patients in the septic shock group and 60 patients in the sepsis group after matching. The levels of C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), serum amyloid A (SAA), soluble endothelial protein C receptor (sEPCR), endothelial cell-specific molecule 1 (ESM-1), clusterin (CLU), and the Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score and Sequential Organ Failure Assessment (SOFA) score at admission were compared between the two groups. Cox proportional hazards regression analysis was used to identify the factors influencing septic shock, and a predictive model for septic shock was constructed and internally validated using the receiver operating characteristic (ROC) curve. Kaplan-Meier survival curves were plotted to analyze the differences in survival prognosis among patients with different expression levels of the indicators. Results After matching, there were no statistically significant differences in general information between the two groups (
7. Experimental study of irisin alleviates house dust mite-induced airway epithelial cells inflammation and apoptosis via the NF-κB and JNK signaling pathways
Ying LI ; Wei YAO ; Meng WANG ; Zhihong YU ; Yuanqi GONG ; Haibing LAN ; Xiefei QI
Chinese Journal of Clinical Pharmacology and Therapeutics 2022;27(10):1106-1112
AlM: To explore the effects of irisin on house dust mite (HDM)-induced inflammation and apoptosis in human airway epithelial cells. METHODS: The human bronchial epithelial cell (16HBE) were cultured with in RPMI1640 culture medium with 10% of fetal bovine serum. After cells reached 85% confluence, the medium was replaced with serum-free culture medium for 12 h. Then the 16HBE cells were treated with various concentrations of HDM (0, 400, 800, 12 00 U/mL) for 24 h. Reactive oxygen species assay kit was used to detected the intracellular ROS generation. And qPCR was used to measure the interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α) mRNA expression of the HDM-induced 16HBE cell. The cells were pre-treated with or without irisin for 2 h before exposure to various concentration of HDM for 24 h. Then reactive oxygen species assay kit was used to detected the intracellular ROS generation. The IL-6, TNF-α mRNA expression of 16HBE cell were measured by qPCR. Meanwhile, the phosphorylated and total P65 NF-κB and JNK proteins were detected by western blot. The pro-apoptosis protein cleaved-caspase3BAX and the anti-apoptosis protein were also detected by western blot. RESULTS: The quantitative assay showed that intracellular ROS in different concentrations of HDM stimulus group were obviously higher than NC group (P < 0.05). And RT-PCR analysis showed a higher expression level of pro-inflammatory cytokine TNF-α and IL-6 mRNA in different concentrations of HDM than in NC group (P < 0.05). Compared with the HDM group, Irisin significantly decreased the level of intracellular ROS of the 16HBE cells (P < 0.05). The released of the pro-inflammatory cytokine TNF-α and IL-6 mRNA was also decreased in irisin treated 16HBE cells (P < 0.05). And compared with control group, BCL-XL anti-apoptosis protein level was decreased and BAX and c-caspase3 pro-apoptosis protein levels were increased in HDM group (P < 0.05), irisin intervention significantly increased the level of BCL-XL and decreased the levels of BAX and cleaved-caspase 3 (P < 0.05). Compared the control group, phosphorylated P65 NF-κB and JNK protein levels were significantly increased after HDM stimulated (P < 0.05), and irisin intervention decreased the protein levels of phosphorylated P65 NF-κB and JNK (P < 0.05). CONCLUSlON: Irisin can effectively improve the inflammation and apoptosis of HDM-induced 16HBE cells, and this protective effect may be related to its inhibition of NF-κB and JNK MAPK signaling pathways. Irisin may be a potential drug for treating lung inflammation.
8.A comparison of clinicopathological features and prognosis between lymph node dissection extents of pancreatic cancer patients undergoing pancreaticoduodenectomy
Yefan YANG ; Sha ZHAO ; Yuxi GONG ; Boya ZHAI ; Zhihong ZHANG
Chinese Journal of General Surgery 2021;36(11):822-825
Objective:To compare the clinical, pathological features and prognosis of patients who underwent pancreaticoduodenectomy with standard or extended lymph node dissection for pancreatic ductal adenocarcinoma.Methods:A retrospective study was performed on 158 pancreatic head cancer patients who underwent radical resection at the First Affiliated Hospital of Nanjing Medical University from Jul 2017 to Feb 2019. The clinicopathological characteristics and prognosis between the standard dissection group and the extended dissection group were compared. The relationship between the number of examined lymph nodes, positive lymph nodes, and the lymph node ratio, together with their relationship with survival were analyzed.Results:Survival analysis showed no statistical difference in survival between the standard resection group and the extended resection group ( P=0.99). There were statistical differences in gender and age composition between the two group, but no significant differences in operation time, blood loss, or postoperative complications were found. Patients with less examined lymph nodes tended to be of stage N0. examined lymph nodes is positively correlated with positive lymph nodes but is not significantly correlated with lymph node ratio. Positive lymph nodes is strongly correlated with lymph node ratio. The location of lymph node metastasis was not survival-related. Conclusions:There is no prognostic difference between standard lymph node dissection and extended lymph node dissection in pancreatic cancinoma patients after Whipple procedure.
9.Progress of classification and prognosis of diffuse large B-cell lymphoma
Yuxi GONG ; Boya ZHAI ; Yefan YANG ; Zhihong ZHANG
Journal of Leukemia & Lymphoma 2021;30(9):565-568
Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma, with high clinical and biological heterogeneity. Only 60% of patients can benefit from standard immunochemotherapy. Looking for new clinical parameters and biomarkers to better classify and stratify the prognosis of DLBCL patients has been the focused area in recent years. This article reviews the classifications and their prognostic significances of DLBCL by analyzing the related studies of genome and transcriptome.
10.Relationship between clinicopathological features and prognosis of pancreatic ductal adenocarcinoma
Yefan YANG ; Sha ZHAO ; Boya ZHAI ; Yuxi GONG ; Xiang ZHANG ; Zhihong ZHANG
Chinese Journal of Pathology 2021;50(8):924-928
Objective:To investigate the relationship between clinicopathologic features and prognosis of pancreatic ductal adenocarcinoma located in the head of pancreas.Methods:A retrospective study was performed on 169 patients undergoing radical resection for pancreatic head cancer collected in the First Affiliated Hospital with Nanjing Medical University from January 2018 to April 2019. Univariate analysis and multivariate analysis were performed.Results:Patient′s age, tumor differentiation, tumor maximum diameter, resection margin (several resection margins including portal vein groove resection margin, posterior resection margin, and uncinate resection margin), number of positive lymph nodes, number of regional lymph node dissected, and some preoperative and postoperative indicators were associated with prognosis ( P<0.05). Direct tumor invasion of organs and surrounding tissues, perineural and vascular invasion, pathologic variants etc. had no statistical significance for survival time. Patient′s age, maximum tumor diameter, degree of differentiation, uncinate incision margin, number of regional lymph nodes dissected, and preoperative CA19-9 were independent factors affecting prognosis. Patients older than 74 years of age, with tumors larger than 3 cm in diameter, poorly differentiated, less than 7 regional lymph node dissected, positive uncinate margin, and preoperative CA19-9 higher than 1.5×10 5 U/L were independent risk factors in patients with pancreatic head cancer. Conclusions:Old age, tumor lager than 3 cm, poor differentiation, low examined lymph nodes, direct uncinate margin involvement and (or) with preoperative CA19-9 higher than 1.5×10 5 U/L are related to poor prognosis of head pancreatic cancer.


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