1.Protective effect of Qingjie Huagong decoction on pancreatic tissue of mice with severe acute pancreatitis by regulating the NOD-like receptor protein 3/Toll-like receptor 4/nuclear factor-kappa B signaling pathway
Minchao FENG ; Baijun QIN ; Fang LUO ; Kai LI ; Ning WANG ; Guozhong CHEN ; Xiping TANG
Journal of Clinical Hepatology 2024;40(2):343-350
ObjectiveTo investigate the therapeutic effect of Qingjie Huagong decoction (QJHGD) on a mouse model of severe acute pancreatitis (SAP) and the mechanism of action of QJHGD against inflammatory response. MethodsA total of 36 male C57BL/6J mice were randomly divided into blank group, model group, Western medicine group (ulinastatin), and low-, middle-, and high-dose QJHGD groups, with 6 mice in each group. All mice except those in the blank group were given 5% sodium taurocholate by retrograde pancreaticobiliary injection to establish a model of SAP. After modeling, the mice in the low-, middle-, and high-dose groups were given QJHGD (1, 2, and 4 g/kg, respectively) by gavage, and those in the Western medicine group were given intraperitoneal injection of ulinastatin (5×104 U/kg), for 7 days in total. HE staining was used to observe the histopathological changes of the pancreas; ELISA was used to measure the levels of α-amylase, lipase, interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-18 (IL-18), and tumor necrosis factor-α (TNF-α) in mice; RT-qPCR was used to measure the mRNA expression levels of NOD-like receptor protein3 (NLRP3), Toll-like receptor 4 (TLR4), and nuclear factor-kappa B (NF-κB) in pancreatic tissue; immunohistochemistry was used to measure the positive expression rates of NLRP3, TLR4, and NF-κB in pancreatic tissue; Western blot was used to measure the protein expression levels of NLRP3, TLR4, NF-κB, IL-1β, and IL-6. An analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the blank group, the model group had diffuse destruction of pancreatic tissue structure, focal dilatation of pancreatic lobular septum, pancreatic acinar atrophy, and massive inflammatory cell infiltration, as well as significant increases in the content of α-amylase, lipase, IL-1β, IL-6, IL-8, IL-18, and TNF-α (all P<0.05), the mRNA expression levels and positive expression rates of NLRP3, TLR4, and NF-κB (all P<0.05), and the protein expression levels of NLRP3, TLR4, NF-κB, IL-1β, and IL-6 (all P<0.05). Compared with the model group, the low-, middle-, and high-dose QJHGD groups and the Western medicine group had slightly tighter and more intact structure of pancreatic tissue, ordered arrangement of pancreatic acinar cells, a small amount of inflammatory cell infiltration, and hemorrhagic foci of pancreatic lobules, as well as significant reductions in the content of α-amylase, lipase, IL-1β, IL-6, IL-8, IL-18, and TNF-α (all P<0.05), the mRNA expression levels and positive expression rates of NLRP3, TLR4, and NF-κB (all P<0.05), and the protein expression levels of NLRP3, TLR4, NF-κB, IL-1β, and IL-6 (all P<0.05). ConclusionQJHGD may exert a protective effect on the pancreatic tissue of SAP mice by inhibiting the activation of NLRP3/TLR4/NF-κB signaling pathway-related proteins, reducing the release of inflammatory mediators, and preventing the enhancement of inflammatory cascade response.
2.Effects of Yishen Jiangu Pills on AMPK/Cyclin Y/CDK16 Pathway Expressions and Chondrocyte Autophagy and Apoptosis in Cartilage Tissue of Knee Osteoarthritis Rats
Xiping CHAI ; Shenghua LI ; Mingwang ZHOU ; Wei CHEN ; Xuewen SONG ; Yingying CHAI
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(10):89-95
Objective To investigate the effects of Yishen Jiangu Pills on the expressions of AMPK/Cyclin Y/CDK16 pathway and autophagy and apoptosis-related proteins in cartilage tissue of rats with knee osteoarthritis(KOA);To discuss its mechanism for the treatment of KOA.Methods Totally 60 2-month-old SD rats were selected and randomly divided into sham-operation group,model group,agonist group,and TCM low-,medium-and high-dosage groups,with 10 rats in each group.Except for the sham-operation group,each group underwent medial meniscectomy and cruciate ligamentotomy to establish the KOA rat model,and the corresponding interventions were given for 14 d.Lequesne MG score was used to evaluate rat behavior,morphology of cartilage tissue was observed by HE and Safranin O-fixed green staining,and Mankin score was performed,Western blot was performed to detect expression of AMPK/Cyclin Y/CDK16 pathway proteins and autophagy proteins such as ULK-1,Beclin-1,LC3B,p62 and apoptotic proteins such as Bcl-2,Bax,Caspase-3,Caspase-9 in cartilage tissue,and autophagosome were observed using transmission electron microscopy.Results Compared with the sham-operation group,Lequesne MG score significantly increased in the model group(P<0.01),there was a significant defect in the surface layer of cartilage,thinning of the cartilage layer,disordered arrangement and irregular morphology of chondrocytes,and a significant increase in Mankin score(P<0.01),the expressions of AMPK,Cyclin Y,CDK16,ULK1,Beclin-1,LC3BⅡ/Ⅰ and Bcl-2 protein in cartilage tissue decreased,while the expressions of p62,Bax,Caspase-3 and Caspase-9 protein increased(P<0.01).Compared with the model group,the Lequesne MG scores of rats in the agonist group and TCM high-dosage group were significantly decreased(P<0.01),the TCM high-dosage group showed smoother cartilage surface,more regular arrangement of chondrocytes,basic integrity of cartilage layer structure,weakened cartilage tissue proliferation,and significantly decreased Mankin score(P<0.01),the expressions of AMPK,Cyclin Y,CDK16,ULK1,Beclin-1,LC3BⅡ/Ⅰ and Bcl-2 protein in cartilage tissue of rats in the agonist group and TCM medium-and high-dosage groups significantly increased(P<0.05,P<0.01),while the expressions of p62,Bax,Caspase-3 and Caspase-9 protein significantly decreased(P<0.05,P<0.01).Conclusion Yishen Jiangu Pills may promote chondrocyte autophagy and inhibit cell apoptosis by activating the AMPK/Cyclin Y/CDK16 pathway in cartilage tissue of KOA model rats,thus reduce cartilage damage.
3.Effect of Banxia Xiexintang-containing Intestinal Absorption Solution on Migration and Invasion of PMN-MDSCs in Gastric Cancer Microenvironment
Jingjing WEI ; Zhongbo ZHU ; Xiping LIU ; Peiqing LI ; Qiming CHEN ; Lirong DAI ; Lijuan SHI ; Haijing DUAN ; Qingmiao WANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(10):48-57
ObjectiveTo observe the effect of Banxia Xiexintang containing intestinal absorption solution (BXCIAS) on migration and invasion of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in gastric cancer microenvironment. MethodThe complex solution (containing 0.63 g·mL-1 crude drug) was prepared. Gastric cancer cells were subjected to non-contact co-culture with PMN-MDSCs in Transwell chamber to create gastric cancer microenvironment. Cell counting kit-8 (CCK-8) assay was used to screen the optimal intervention concentration and time of BXCIAS on PMN-MDSCs for subsequent experiment. The blank group, model group, FAK inhibitor group, and BXCIAS groups (26%, 18%, and 10%) were designed. Scratch assay and Transwell assay were employed to detect the migration and invasion ability of PMN-MDSCs, and enzyme-linked immunosorbent assay (ELISA) to measure the expression of vascular endothelial cell growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in tumor microenvironment. The expression levels of PMN-MDSCs pathway-related proteins FAK, phosphorylated (p)-FAK, protein tyrosine kinase (Src), and p-Src were detected by Western blot. ResultThe inhibition rates of PMN-MDSCs by 5%, 50%, 75%, and 100% BXCIAS at 48 h were higher than those at 24 h (P<0.05, P<0.01). The inhibition rate of PMN-MDSCs by 50% BXCIAS at 72 h was lower than that at 48 h (P<0.01), and the inhibition rates by 5% and 100% BXCIAS at 72 h were higher than those at 48 h (P<0.05, P<0.01). There was no significant difference in the inhibition rate by other concentration levels at 48 h. The half-maximal inhibitory concentration (IC50) at 48 h was 18.09%, indicating that 18% BXCIAS and 48 h were the optimal concentration and time, respectively. The migration distance of PMN-MDSCs was large (P<0.01), and the number of migrating and invading cells increased (P<0.01) in the mode group compared with those in the blank group. Compared with model group, FAK inhibitor and BXCIAS at different concentration decreased the migration distance of PMN-MDSCs (P<0.01), and the number of migrating and invading cells (P<0.01), especially the 26% BXCIAS (P<0.01). The expression of PMN-MDSCs pathway-related proteins FAK, p-FAK, Src and p-Src (P<0.01) and the expression of VEGF and MMP-9 (P<0.01) were higher in the model group than in the blank group. Compared with model group, FAK inhibitor and BXCIAS (26%, 18%, 10%) decreased the expression of FAK, p-FAK, and Src (P<0.01), and FAK inhibitor and 18% BXCIAS reduced the expression of p-Src (P<0.01), and the expression of VEGF and MMP-9 (P<0.01). ConclusionBXCIAS can inhibit the migration and invasion of PMN-MDSCs by down-regulating the expression of FAK, p-FAK, Src, and p-Src proteins in the FAK signaling pathway of PMN-MDSCs in gastric cancer microenvironment.
4.Effect of Banxia Xiexintang-containing Intestinal Absorption Solution on PMN-MDSCs Apoptosis in Gastric Cancer Microenvironment
Jingjing WEI ; Zhongbo ZHU ; Xiping LIU ; Peiqing LI ; Qiming CHEN ; Lirong DAI ; Lijuan SHI ; Haijing DUAN ; Qingmiao WANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(10):58-64
ObjectiveTo observe the effect of Banxia Xiexintang (BXT)-containing intestinal absorption solution on the apoptosis of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in gastric cancer microenvironment. MethodBXT-containing intestinal absorption solution was prepared, and gastric cancer cells and PMN-MDSCs were non-contact co-cultured in Transwell chamber to establish gastric cancer microenvironment. Cell counting kit-8 (CCK-8) assay was used to screen the optimal intervention concentration and time of 0-100% BXT-containing intestinal absorption solution prepared by 0.63 g·mL-1 reconstitution solution. Cells were classified into blank group, model group, oxaliplatin group (10 mg·L-1), and BXT (26%, 18%, 10% BXT-containing intestinal absorption solution) group, and the apoptosis of PMN-MDSCs was detected by flow cytometry. The expression of apoptosis-related B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and cysteine-aspartic acid protease-3 (Caspase-3) in PMN-MDSCs was detected by Western blot. ResultAfter treatment for 24 h and 48 h, the PMN-MDSCs-inhibiting rate was increased by 5%, 50%, 75%, and 100% BXT-containing intestinal absorption solution compared with that in the blank group (P<0.05, P<0.01). At 72 h, the PMN-MDSCs-inhibiting rate by 50% BXT-containing intestinal absorption solution was lower than that at 48 h (P<0.01), and the PMN-MDSCs-inhibiting rate by 5%, 75%, and 100% BXT-containing intestinal absorption solution showed no significant difference from that at 48 h. Moreover, the half-maximal inhibitory concentration (IC50) at 48 h was 18.40%. Thus, 18% BXT-containing intestinal absorption solution and 48 h were the optimal intervention concentration and time. The survival rate of PMN-MDSCs in model group was higher than that in the blank group (P<0.05), and the apoptosis rate was lower than that in the blank group (P<0.05). Compared with model group, BXT containing intestinal absorption solution lowered the survival rate and raised apoptosis rate of PMN-MDSCs (P<0.05), particularly the 26% BXT-containing intestinal absorption solution (P<0.05). The expression of Bax and Caspase-3 in PMN-MDSCs was lower in the model group than in the blank group (P<0.05), and the expression of Bcl-2 was higher in the model group than in the blank group (P<0.05). The expression of Caspase-3 in PMN-MDSCs increased (P<0.05) and the expression of Bcl-2 decreased (P<0.05) in oxaliplatin group and BXT group compared with those in the model group. The expression of Bax rose in oxaliplatin group and BXT group (10% BXT-containing intestinal absorption solution) (P<0.05). ConclusionBXT can induce the apoptosis of PMN-MDSCs by regulating the expression of apoptosis-related proteins Bax, Caspase-3, and Bcl-2 in gastric cancer microenvironment.
5.Effect and mechanism of oxycodone hydrochloride on inflammation and neuronal apoptosis in epileptic rats
Xiping CHEN ; Jinzhu HUANG ; Yongge LI
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2023;25(10):1093-1097
Objective To explore the effect of oxycodone hydrochloride on inflammation and neuro-nal apoptosis in epileptic rats through c-Jun amino terminal kinase(JNK)/p38 mitogen activated protein kinase(p38 MAPK)signaling pathway.Methods After epileptic rat model was success-fully constructed,72 epileptic rats were randomly divided into model group,low-,medium-and high-dose oxycodone hydrochloride groups(0.125,0.25 and 0.5 mg/kg),anisomycin(JNK activa-tor 5 mg/kg)and combined group(0.5 mg/kg oxycodone hydrochloride+5 mg/kg anisomycin),with 12 rats in each group.Another 12 healthy rats were selected as control group.In 24 h after the end of administration,the frequency and duration of seizures were recorded for all rats.ELISA was used to detect the serum levels of TNF-α and IL-6,HE staining was employed to observe the his-topathological changes in hippocampal CA1 region,and TUNEL staining was applied to detect the apoptosis of CA1 region neurons.The expression of JNK,p-JNK,p38 MAPK,p-p38 MAPK and Caspase-3 in hippocampal CA1 region was detected by Western blotting.Results Compared with the rats from the control group,those of the model group showed higher frequency and longer du-ration of seizures,higher serum TNF-α and IL-6 levels,increased apoptotic rate of hippocampal CA1 neurons,and elevated p-JNK/JNK ratio,p-p38 MAPK/p38 MAPK ratio and Caspase-3 expression(P<0.05).While low-,medium-and high-dose oxycodone hydrochloride treatment re-versed above changes in frequency and duration of seizures,serum TNF-α and IL-6 levels,neuro-nal apoptosis,p-JNK/JNK ratio,p-p38 MAPK/p38 MAPK ratio and Caspase-3 expression(P<0.05).In the anisomycin group,higher frequency and longer duration of seizures,elevated serum TNF-α and IL-6 levels,increased neuronal apoptotic rate in hippocampal CA1 region,and en-hanced p-JNK/JNK ratio,p-p38 MAPK/p38 MAPK ratio and Caspase-3 expression(P<0.05).Lower frequency and shorter duration of seizures,decreased serum TNF-α and IL-6 levels,and re-duced neuronal apoptotic rate in hippocampal CA1 region were observed in the combined group than the anisomycin group(P<0.05).The combined group obtained statistically lower p-JNK/JNK ratio,p-p38 MAPK/p38 MAPK ratio and Caspase-3 expression in hippocampal CA1 region than the high-dose group,and opposite results than the anisomycin group(0.89±0.12 vs 0.25± 0.05 vs 1.08±0.16,0.81±0.08 vs 0.21±0.04 vs 0.94±0.12,0.79±0.12 vs 0.26±0.04 vs 0.89± 0.14,P<0.05).Conclusion Oxycodone hydrochloride can reduce inflammatory response,im-prove epileptic symptoms and pathological damages,and protect neurons in epileptic rats,which is related to the inhibition of JNK/p38 MAPK signaling pathway.
6.Expression of calcium-binding protein A9 in cervical cancer and its relationship with therapeutic effect
Cancer Research and Clinic 2023;35(11):827-832
Objective:To investigate the expression of calcium binding-protein A9 (S100A9) in cervical cancer and its relationship with the efficacy of TC (paclitaxel+carboplatin) regimen chemotherapy in patients.Methods:A total of 119 patients with cervical cancer who were scheduled to undergo TC regimen chemotherapy in the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture from July 2017 to May 2021 were selected to conduct a prospective study. The tissue samples of all patients were obtained by biopsy before treatment, and the expressions of S100A9, matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) in cervical cancer tissues and paracancerous normal tissues were detected by immunohistochemistry. The correlation of S100A9 expression with MMP-9 and VEGF expressions in cervical cancer tissues were analyzed by using Spearman method. The patients were divided into the effective group (complete remission+partial remission) and the ineffective group (stable disease+progressive disease) according to the effectiveness of chemotherapy, and the expressions of S100A9, MMP-9 and VEGF in cervical cancer tissues of the two groups were compared. The influencing factors for TC regimen chemotherapy efficacy were analyzed by using multivariate logistic regression method.Results:Compared with paracancerous tissues, the positive expression rates of S100A9 [90.76% (108/119) vs. 45.38% (54/119)], MMP-9 [55.46% (66/119) vs. 17.65% (21/119)] and VEGF [78.99% (94/119) vs. 24.37% (29/119)] were all elevated in cervical cancer tissues ( χ2 values were 47.03, 36.69 and 71.09, all P < 0.001). The S100A9 expression in cervical cancer tissues was positively correlated with MMP-9 and VEGF expressions ( r values were 0.619 and 0.784, both P < 0.001). The effective rate of TC regimen chemotherapy was 47.06% (56/119). The positive expression rate of S100A9 in cervical cancer tissues of the effective group was higher than that of the ineffective group [98.21% (55/56) vs. 84.13% (53/63), P < 0.05], while the positive expression rates of MMP-9 [35.71% (20/56) vs. 73.02% (46/63)] and VEGF [67.86% (38/56) vs. 88.89% (56/63)] were lower than those of the ineffective group (both P < 0.001). Multivariate logistic regression analysis showed that clinical stage Ⅳ ( OR = 2.707, 95% CI 1.865-4.119, P < 0.05), lymph node metastasis ( OR = 4.468, 95% CI 3.221-5.823, P < 0.001), deep myometrial invasion ( OR = 5.686, 95% CI 4.308-7.247, P < 0.001), vascular tumor thrombus or parauterine invasion ( OR = 3.758, 95% CI 2.584-5.163, P < 0.001), MMP-9 positive expression in cancer tissues ( OR = 3.904, 95% CI 2.876-5.228, P < 0.001) and VEGF positive expression in cancer tissues ( OR = 2.609, 95% CI 1.793-4.052, P < 0.05) were the risk factors affecting the TC regimen chemotherapy efficacy, while the S100A9 positive expression in cancer tissues was the protective factor for TC regimen chemotherapy efficacy ( OR = 0.660, 95% CI 0.417-0.854, P < 0.05). Conclusions:The expression of S100A9 in cervical cancer tissues increases and correlates with MMP-9 and VEGF expressions. The high expression of S100A9 could increase the effectiveness of TC regimen chemotherapy in cervical cancer patients, while clinical stage Ⅳ, lymph node metastasis, deep muscle invasion, vascular tumor thrombus or parauterine invasion, MMP-9 positive expression and VEGF positive expression may increase the risk of ineffective chemotherapy with TC regimen in patients.
7.Clinical observation of Qingjie Huagong Decoction combined with western medicine in the treatment of severe acute pancreatitis complicated with cholelithiasis (bile duct stones)
Rihui ZHENG ; Guozhong CHEN ; Xiping TANG ; Tiechao YUAN ; Xin YANG ; Baijun QIN ; Caixing XIE
International Journal of Traditional Chinese Medicine 2022;44(2):145-149
Objective:To evaluate the clinical efficacy of TCM Qingjie Huagong Decoction combined with routine internal medicine in the treatment of severe acute pancreatitis with cholelithiasis (bile duct stones) in the early stage.Methods:Thirty-two patients with severe acute pancreatitis combined with cholelithiasis in the first affiliated Hospital of GuangXi University of Traditional Chinese Medicine were selected and randomly divided into two groups with 16 in each, both groups were treated for 14 days. Serum amylase (AMS) was detected by iodine-starch colorimetry, GOT and GPT were detected by continuous monitoring method, and CRP, IL-6 and procalcitonin (PCT) were detected by immune transmission turbidimetry. Acute Physiological and Chronic Health Score Ⅱ (APACHE Ⅱ), CT Severity Index Score (CTSI) and Modified Marshall Score were used to evaluate the severity of SAP. The recovery time of body temperature, the relief time of abdominal distension pain, the recovery time of bowel sounds and the total hospital stay were observed and recorded to evaluate the clinical effect.Results:The total effective rate was 93.8% (15/16) in the treatment group and 75.0% (12/16) in the control group. There was significant difference between the two groups ( χ2=8.19, P=0.042). After treatment, the level of AMS, WBC, CRP, PCT, AST, ALT and IL-6 in the treatment group were lower than those in the control group ( t values were 14.3, 7.24, 9.63, 5.48, 7.05, 7.33, 28.34, respectively, all Ps<0.05); After treatment, the time for body temperature to return to normal [(2.91±0.12)d vs. (3.78±0.38)d, t=8.76], the time for relief of abdominal distension pain [(4.77±0.68)d vs. (7.13±1.55)d, t=9.52], the time for recovery of bowel sounds [(3.90±1.80)d vs. (4.89±1.38)d, t=2.98] and the total hospital stay [(22.60±2.80)d vs. (30.37±3.89)d, t=7.88] in the treatment group were all significantly shorter than those in the control group ( P<0.01); APACHE Ⅱ, CTSI and the Modified Marshall Score in the treatment group were lower than those in the control group ( t values were 11.82, 12.72, 7.71, respectively, all Ps<0.01). Conclusion:Qingjie Huagong Decoction combined with ERCP and conventional western medicine therapy can reduce the level of inflammation in patients with cholelithiasis in the early stage of SAP, relieve clinical symptoms and improve clinical efficacy.
8.Diagnosing lung cancer through metabolic fingerprint based on machine learning
Yuxin ZHANG ; Chengwen HE ; Lin HUANG ; Kun QIAN ; Wei CHEN ; Yin JIA ; Jingjing HU ; Qin WEI ; Xiping WANG ; Shanrong LIU
Chinese Journal of Laboratory Medicine 2022;45(3):226-233
Objective:To screen out the differentially regulated metabolites by the analysis of serum metabolic fingerprints, and to provide potential biomarkers for diagnosis of lung cancer.Methods:A total of 228 subjects were enrolled in Changhai Hospital from January 27, 2021 to June 4, 2021, including 97 newly diagnosed lung cancer patients and 131 healthy individuals. Serum samples were collected from the enrolled cohort according to a standard procedure, and the enrolled cohort was divided into a training set and a completely independent validation set by stratified random sampling. The metabolic fingerprints of serum samples were collected by previously developed nano-assisted laser desorption/ionization mass spectrometry (nano-LDI MS). After age and gender matching of the training set, a diagnostic model based on serum metabolic fingerprints was established by machine learning algorithm, and the classification performance of the model was evaluated by receiver operating characteristic (ROC) curve.Results:Serum metabolic fingerprint for each sample was obtained in 1 minute using a novel nano-LDI MS, with consumption of only 1 μl original serum sample. For the training set, the area under ROC curve (AUC) of the constructed classifier for diagnosis of lung cancer was 0.92 (95% CI 0.87-0.97), with a sensitivity of 89% and specificity of 89%. For the independent validation set, the AUC reached 0.96 (95% CI 0.90-1.00) with a sensitivity of 91% and specificity of 94%, which showed no significant decrease compared to training set. We also identified a biomarker panel of 5 metabolites, demonstrating a unique metabolic fingerprint of lung cancer patients. Conclusion:Serum metabolic fingerprints and machine learning were combined to establish a diagnostic model, which can be used to distinguish between lung cancer patients and healthy controls. This work sheds lights on the rapid metabolic analysis for clinical application towards in vitro diagnosis.
9.Study on the effects of Qingjie huagong decoction on the regulation of intestinal flora and intestinal mucosal barrier in severe acute pancreatitis model rats
Baijun QIN ; Xiping TANG ; Xin YANG ; Lei YANG ; Minchao FENG ; Chi ZHANG ; Xiaohua HONG ; Yanmei LAN ; Guozhong CHEN
China Pharmacy 2022;33(15):1825-1832
OBJECTIVE To explore the the reg ulation of intestinal flora and effects of Qingjie huagong decoction on intestinal mucosal barrier in severe acute pancreatitis (SAP)mode rats . METHODS SAP rat model was induced by intraperitoneal injection of caerulein and lipopolysaccharide.The survival state of rats in each group were observed.The levels of serum amylase ,interleukin 10(IL-10),IL-18 and IL- 1β in serum were all detected. The pathological changes of pancreatic and small intestinal tissue were observed. The expressions of Occludin,ZO-1 and HMGB1 were detected in small intestinal tissue of rats. The structure and relative abundance of intestinal microflora in rats were detected by 16S rRNA high throughput sequencing. RESULTS After the intervention of Qingjie huagong decoction ,abdominal distension symptoms of SAP model rats were significantly relieved ,and their mental state recovered better ;the levels of serum amylase and IL- 18 in serum were decreased significantly (P<0.05),while the level of IL- 10 was increased significantly (P<0.05). The necrotic area of pancreatic tissue and the infiltration of inflammatory cells were reduced , the degree of intestinal epithelial cell structural disorder was alleviated ,and the shedding of intestinal mucosal epithelium was reduced.The protein expression of HMGB 1 in small intestinal tissue was decreased significantly (P<0.05),and the protein expression of Occludin and ZO- 1 were increased significantly . Results of 16S rRNA high throughput sequencing showed that Qingjie huagong decoction could increased the relative abundance of probiotics such as Bacteroidea and Lactobacillus in rat intestine ,reduced the colonization of harmful bacteria such as Firmicutes. CONCLUSIONS Qingjie huagong decoction can improve the intestinal barrier by up-regulating the expression of Occludin and ZO- 1 in small intestinal tissue and down-regulating the protein expression of HMGB 1. It can also adjust the relative abundances of different flora to protect the intestinal tract.
10.The clinical application value of potentially inappropriate drug assessment system in elderly inpatients
Pengying GU ; Shilian HU ; Xiping DING ; Peng CHEN ; Song JIN ; Zhetao ZHANG ; Nan LI ; Sijie YAO
Chinese Journal of Geriatrics 2021;40(8):1045-1049
Objective:To explore the clinical value of the geriatric potentially inappropriate medication(PIM)evaluation system in elderly inpatients.Methods:As a prospective cohort study, 203 elderly inpatients with polypharmacy were randomly divided into the control group and experimental group.Geriatric PIM evaluation system(based on the criteria for judging potential inappropriate drug use in Chinese elderly 2017 edition)on wechat platform was applied to patients of experimental group.During the 6 months, the number of elderly syndromes, types of drugs, the days in hospitalization, readmission rates and all-cause mortality were compared between two groups.Results:The age of 203 elderly inpatients ranged from 60 to 94(77.30±10.34)years, including 121 males and 82 females.The morbidity proportion of top five diseases were 69.95%(142/203)in cerebral infarction(non-acute phase), 62.07%(126/203)in hypertension, 24.14%(49/203)in coronary heart disease, 9.85%(20/203)in atrial fibrillation, and 6.40%(13/203)in cardiac insufficiency.The 97.53%(198/203)of elderly hospitalized patients had at least one senile syndrome, the average was 4.3±2.0.Insomnia, fall and frailty accounted for 32.87%(15/198), 28.45%(56/198)and 13.66%(27/198)respectively.Compared with the control group, the average length of stay in hospital in the experimental group significantly decreased[(16.38±4.29) vs.(21.32±6.10)d, t=2.438、 P=0.025], the number of senile syndrome, the score of fall, weakness and the re-admission rate were also decreased significantly(3.11±2.14 vs.4.32±1.50, t=0.854、 P=0.032; 6.19±1.35 vs.8.61±3.22, t=4.078、 P=0.044; 3.94±1.92 vs.5.65±1.34, t=2.843、 P=0.038; 9.81%(10/102) vs.1.98%(2/101), χ2=4.772、 P=0.029), and the frequency of PIM was significantly different between two groups(417.36±49.21 vs.210.25±38.23, t=2.136、 P=0.034). Conclusions:After making the drug adjustment on the elderly inpatients with multiple drugs, PIM evaluation system for the elderly are able to reduce the incidence of geriatric syndrome, shorten the length of stay in hospital, improve the rational use of drugs, and enhance the quality of life of the elderly patients.

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