1.Effect and mechanism of Biejiajian Pill on subcutaneous xenograft tumor model of hepatocellular carcinoma Huh7 cells
Lu LU ; Huanling CHEN ; Jian XU ; Yuanqin DU ; Xiaoli LIU ; Yingsheng WU ; Chengting WU ; Wei BAN ; Jingjing HUANG ; Hongna HUANG
Journal of Clinical Hepatology 2026;42(1):125-133
ObjectiveTo investigate the inhibitory effect of Biejiajian Pills (BJJW) on the growth of liver cancer, as well as its potential mechanism in mediating the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway through mitochondrial energy metabolism. MethodsHuman hepatoma Huh7 cells were used to establish a nude mouse model of subcutaneous xenograft tumor. A total of 18 tumor-bearing nude mice were randomly divided into model group, BJJW group (2.2 g/kg), and metformin group (250 mg/kg), and the corresponding drug was given by gavage for 14 consecutive days. Tumor volume and weight were monitored during the experiment; HE staining was used to observe histopathological changes; the levels of reactive oxygen species (ROS) and adenosine triphosphate (ATP) in tumor tissue were measured; immunohistochemistry and Western blotting were used to measure the expression levels of proteins associated with the AMPK/mTOR pathway. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the Tukey’s test was used for further comparison between two groups; the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups, and the Dunn’s test was used for further comparison between two groups. ResultsCompared with the model group, the BJJW group had a tumor inhibition rate of 45.73%, with significant reductions in both tumor volume and weight (P<0.01). Pathological examination showed that compared with the model group, the BJJW group had a significant reduction in the number of tumor cells and the presence of extensive necrosis. Mechanistic studies showed that compared with the model group, the BJJW group had a significant increase in ROS level (P<0.001) and a significant reduction in ATP level (P<0.001), as well as significant increases in p-AMPK/AMPK ratio (0.81±0.20 vs 0.13±0.04, P<0.01) and p-ULK1/ULK1 ratio (0.69±0.17 vs 0.18±0.13, P<0.01) and a significant reduction in p-mTOR/mTOR ratio (1.34±0.16 vs 3.20±0.62, P<0.01). ConclusionBJJW may inhibit the growth of liver cancer by inducing mitochondrial energy metabolism dysfunction, increasing the level of ROS, reducing the level of ATP, and activating the AMPK/mTOR signaling pathway.
2.Distribution and drug resistance of pathogens causing bloodstream infections in neonatal intensive care units of Henan Province from 2014 to 2023
Lu XU ; Jing JIA ; Dongyu ZHANG ; Guizhen ZHANG ; Hongna SHI
Chinese Journal of Nosocomiology 2025;35(22):3436-3441
OBJECTIVE To explore the distribution and drug resistance trends of the main pathogens causing blood-stream infections(BSI)in neonatal intensive care unit(NICU)of Henan Province from 2014 to 2023 so as to pro-vide bases for prevention and control of hospital-associated infections in the neonates and reasonable use of antibi-otics in the whole province.METHODS The data regarding to the pathogens causing BSI in the NICU neonates and drug resistance were retrospectively collected from Jan.2014 to Dec.2023,and the statistical analysis was per-formed by SPSS 26.0 and WHONET 5.6 software.RESULTS Totally 27,984 strains of pathogens were collected from 2014 to 2023,13,547(48.41%)of which were gram-negative bacteria,and 14,437(51.59%)were gram-pos-itive bacteria.Klebsiella pneumoniae(4221 strains,15.08%),Escherichia coli(3735 strains,13.35%),Acine-tobacter baumannii(1288 strains,4.60%),Enterobacter cloacae(847 strains,3.12%)and Pseudomonas aerugi-nosa(655 strain,2.34%)were the major species of gram-negative bacteria;Staphylococcus aureus(4545 strains,16.24%),Staphylococcus epidermidis(3306 strains,11.81%),Staphylococcus haemolyticus(2048 strains,7.32%),Staphylococcus hominis(1085 strains,3.88%)and Enterococcus faecalis(946 strains,3.38%)were the predominant species of gram-positive bacteria.The drug resistant analysis indicated that the drug resistance rate of the K.pneumoniae strains to imipenem showed an upward trend during the past six years,peaking at 44.23%,and it began to decline in 2021;though the drug resistance rate of the E.coli strains to imipenem showed some fluctuations,it gener-ally presented a downward trend,peaking at 7.00%.The drug resistance rates of the K.pneumoniae strains to the third generation of cephalosporins and carbapenems were higher than those of the E.coli,and there was significant differ-ence in the antimicrobial prevalence trend between the two species of Enterobacter during the ten years(P<0.05).CONCLUSIONS K.pneumoniae and coagulase-negative Staphylococcus are dominant among the pathogens causing BSI in the ICU neonates of the whole province,and the isolation rates of drug-resistant strains are high.It is grossly necessary for the reasonable clinical use of antibiotics to carry out the bacterial drug resistance surveillance.
3.Distribution and drug resistance of pathogens causing bloodstream infections in neonatal intensive care units of Henan Province from 2014 to 2023
Lu XU ; Jing JIA ; Dongyu ZHANG ; Guizhen ZHANG ; Hongna SHI
Chinese Journal of Nosocomiology 2025;35(22):3436-3441
OBJECTIVE To explore the distribution and drug resistance trends of the main pathogens causing blood-stream infections(BSI)in neonatal intensive care unit(NICU)of Henan Province from 2014 to 2023 so as to pro-vide bases for prevention and control of hospital-associated infections in the neonates and reasonable use of antibi-otics in the whole province.METHODS The data regarding to the pathogens causing BSI in the NICU neonates and drug resistance were retrospectively collected from Jan.2014 to Dec.2023,and the statistical analysis was per-formed by SPSS 26.0 and WHONET 5.6 software.RESULTS Totally 27,984 strains of pathogens were collected from 2014 to 2023,13,547(48.41%)of which were gram-negative bacteria,and 14,437(51.59%)were gram-pos-itive bacteria.Klebsiella pneumoniae(4221 strains,15.08%),Escherichia coli(3735 strains,13.35%),Acine-tobacter baumannii(1288 strains,4.60%),Enterobacter cloacae(847 strains,3.12%)and Pseudomonas aerugi-nosa(655 strain,2.34%)were the major species of gram-negative bacteria;Staphylococcus aureus(4545 strains,16.24%),Staphylococcus epidermidis(3306 strains,11.81%),Staphylococcus haemolyticus(2048 strains,7.32%),Staphylococcus hominis(1085 strains,3.88%)and Enterococcus faecalis(946 strains,3.38%)were the predominant species of gram-positive bacteria.The drug resistant analysis indicated that the drug resistance rate of the K.pneumoniae strains to imipenem showed an upward trend during the past six years,peaking at 44.23%,and it began to decline in 2021;though the drug resistance rate of the E.coli strains to imipenem showed some fluctuations,it gener-ally presented a downward trend,peaking at 7.00%.The drug resistance rates of the K.pneumoniae strains to the third generation of cephalosporins and carbapenems were higher than those of the E.coli,and there was significant differ-ence in the antimicrobial prevalence trend between the two species of Enterobacter during the ten years(P<0.05).CONCLUSIONS K.pneumoniae and coagulase-negative Staphylococcus are dominant among the pathogens causing BSI in the ICU neonates of the whole province,and the isolation rates of drug-resistant strains are high.It is grossly necessary for the reasonable clinical use of antibiotics to carry out the bacterial drug resistance surveillance.
4.Effect of amino acid metabolic reprogramming on immune microenvironment of hepatocellular carcinoma
Xiaoli LIU ; Qinwen TAN ; Jian XU ; Huanling CHEN ; Jie YU ; Lu LU ; Mingkan DAI ; Jingjing HUANG ; Hongna HUANG ; Dewen MAO
Journal of Clinical Hepatology 2024;40(12):2531-2537
Tumor immune microenvironment is a local external tumor environment composed of tumor immune cells and the cytokines secreted by these cells, and it plays a regulatory role in the development and progression of tumors. In the treatment of hepatocellular carcinoma, amino acid metabolism and its reprogramming of proliferating cell metabolism have attracted more and more attention, showing potential in regulating the tumor immune microenvironment. Although amino acid metabolic reprogramming is regarded as a novel approach for tumor therapy, its specific mechanism remains unclear in the regulation of tumor immunity in hepatocellular carcinoma. This article discusses the mechanism of action of amino acid metabolism in the tumor immune microenvironment of hepatocellular carcinoma and its application prospect in clinical practice, in order to provide new ideas for immunotherapy for liver cancer.
5.Regulatory effects of short-chain fatty acids on oxidative stress and activation of pancreatic stellate cells
Hongna LU ; Feng XU ; Qiubo ZHANG ; Ting WENG ; Liangshun ZHANG ; Xianpeng LI
Chinese Journal of Pancreatology 2024;24(3):210-215
Objective:To explore regulatory effects of short-chain fatty acids (SCFA) on hypoxia-induced oxidative stress and activation of pancreatic stellate cells (PSCs) .Methods:PSCs were cultured in normoxia or hypoxia conditions to establish normoxia or hypoxia group. PSCs were pre-treated with SCFA working solution (10 mmol/L sodium acetate, 0.5 mmol/L sodium propionate and 0.5 mmol/L sodium butyrate), and then cultured in hypoxia conditions to establish the hypoxia-SCFA group. PSCs pre-treated by normal saline was set as the hypoxia-control group. The relative growth viability of the cells was detected by the CCK-8 assay. Relative levels of reactive oxygen species (ROS) were detected by DCFH-DA fluorescence probe method. The mitochondrial membrane potential was detected by JC-1 fluorescence probe. Protein expression of cyclin-associated marker cyclin A and cyclin D, hypoxic marker HIF1α, activation marker α-SMA, and antioxidant marker NRF2 and HO-1 was detected by western blotting.Results:The relative viability of PSCs in hypoxia group was significantly higher than that in normoxia group at 48 h (1.23±0.05 vs 0.99±0.04), but the relative viability of hypoxia-SCFA group was significantly lower than that of the hypoxic-control group at both 36 h and 48 h (0.69±0.01 vs 0.86±0.03, 0.86±0.02 vs 1.25±0.05). The relative level of ROS was significantly higher in hypoxia group than normoxia group (1.74±0.11 vs 1.00±0.10). The relative level of ROS was significantly lower in the hypoxia-SCFA group than the hypoxia-control group (1.39±0.14 vs 1.66±0.11). The fluorescence signals of JC-1 polymer in hypoxia group were significantly higher than those in normoxia group (1.36±0.05 vs 1.00±0.11), whereas the fluorescence signals of JC-1 polymer were significantly lower in hypoxia-SCFA group than in hypoxia-control group (1.11±0.03 vs 1.32±0.06). The expression of cyclin A, cyclin D, HIF1α, α-SMA, NRF2, and HO-1 was significantly higher in hypoxia group than those in normoxia group (1.19±0.01 vs 0.63±0.02, 0.93±0.02 vs 0.83±0.03, 1.18±0.07 vs 0.41±0.02, 1.19±0.14 vs 0.66±0.04, 1.22±0.11 vs 0.61±0.04, 1.28±0.12 vs 0.68±0.02), but the expression of cyclin A, cyclin D, α-SMA, NRF2, and HO-1 in Hypoxia-SCFA group was significantly lower than those in hypoxia-control group (0.79±0.04 vs 1.15±0.03, 0.88±0.01 vs 0.95±0.03, 0.87±0.01 vs 1.18±0.05, 0.84±0.01 vs 1.22±0.04, and 0.92±0.02 vs 1.27±0.06). All these differences were statistically significant (all P values <0.05) . Conclusions:SCFA significantly improves the oxidative stress state of PSCs under hypoxic conditions, maintains the stability of mitochondrial membrane potential, and inhibites hypoxia-induced activation of PSCs.
6.Value of AB classification combined with Arima classification for determining the invasion depth of superficial esophageal squamous cell carcinoma
Hongna LU ; Feng XU ; Xuesong ZHANG ; Yao WANG ; Yaohui WANG ; Xi DENG ; Wenying GUO ; Ting WENG ; Liangshun ZHANG ; Tingsheng LING
Chinese Journal of Digestive Endoscopy 2024;41(5):372-378
Objective:To investigate the clinical value of AB classification combined with Arima classification for predicting the invasion depth of superficial esophageal squamous cell carcinomas (SESCC).Methods:From July 2017 to December 2022, 76 cases of SESCC receiving endoscopic submucosal dissection and intra-epithelial papillary capillary loops (IPCL) AB classification as type B2 in Ningbo Medical Center Lihuili Hospital and Jiangsu Province Hospital of Chinese Medicine were included in the study. IPCL was reclassified according to Arima classification. The depth of infiltration determined by pathology was the gold standard. The sensitivity, the specificity, the positive predictive value and the negative predictive value of B2-Arima combined classification in predicting the invasion depth of SESCC were analyzed.Results:In the 76 cases of type B2 IPCL lesions, 31 cases (40.79%) were T1a-MM/T1b-SM1 SESCC. The sensitivity, the specificity, the positive predictive value, the negative predictive value and the diagnostic accuracy of type B2 IPCL to predict T1a-MM/T1b-SM1 SESCC were 70.45% (31/44), 79.64% (176/221), 40.79% (31/76), 93.12% (176/189), and 78.11% (207/265), respectively. After Arima classification, the above corresponding indicators of type B2-4ML and type B2-AVA-4M IPCL in predicting T1a-MM/T1b-SM1 SESCC were 61.36% (27/44), 88.24% (195/221), 50.94% (27/53), 91.98% (195/212), 83.77% (222/265) and 38.64% (17/44), 94.57% (209/221), 58.62% (17/29), 88.56% (209/236), 85.28% (226/265), respectively.Conclusion:B2 IPCL combined with Arima classification can improve the diagnostic accuracy of T1a-MM/T1b-SM1 ESSCC.
7.Application of preoperative pre-rehabilitation in elderly patients with knee arthroplasty combined with sarcopenia
Weihong ZHANG ; Peixia WANG ; Hongna MA ; Hui ZHAO ; Yaming TIAN ; Huiping XU
Chinese Journal of Modern Nursing 2023;29(7):867-872
Objective:To investigate the application effect of preoperative prerehabilitation in elderly patients with knee arthroplasty combined with sarcopenia.Methods:A total of 164 elderly patients who were hospitalized and underwent artificial knee arthroplasty combined with sarcopenia in Department of Orthopedics of the First Affiliated Hospital of Zhengzhou University from July 2020 to December 2021 were included by the convenient sampling method. According to random number table method, they were divided into the control group and the observation group, with 82 cases in each group. The control group received routine preoperative nursing, and the observation group received preoperative pre-rehabilitation intervention on the basis of the control group. Knee range of motion, Hospital for Special Surgery Knee Score (HSS) , skeletal muscle mass index and grip strength were evaluated before intervention and 1 month after operation. Length of stay and postoperative complications were recorded and compared between the two groups.Results:Knee range of motion, HSS of two groups at 1 month after operation were higher than those before intervention, and the differences were statistically significant ( P<0.05) . One month after surgery, the knee range of motion, HSS and grip strength of the observation group were higher than those of the control group, and the differences were statistically significant ( P<0.05) . The skeletal muscle mass index of the observation group was higher one month after surgery than before intervention, but the difference was not statistically significant ( P>0.05) . The hospitalization time of observation group was shorter than control group, and the difference was statistically significant ( P<0.05) . The incidence of complications in the observation group and control group was respectively 15.85% (13/82) and 39.02% (32/82) , and the difference was statistically significant ( P<0.05) . Conclusions:Preoperative rehabilitation can effectively improve the knee range of motion and joint function of elderly patients with sarcopenia after knee rarthroplasty, alleviate sarcopenia, shorten the length of hospital stay and reduce postoperative complications.
8.Effects of nurse-patient cooperative rehabilitation model based on rapid recovery concept in patients with avascular necrosis of femoral head
Weihong ZHANG ; Yang WANG ; Hongna MA ; Hui ZHAO ; Peixia WANG ; Huiping XU
Chinese Journal of Modern Nursing 2023;29(13):1782-1785
Objective:To explore the effect of nurse-patient cooperative rehabilitation model based on rapid recovery concept on the rehabilitation effect of patients with avascular necrosis of the femoral head undergoing artificial hip replacement.Methods:Convenience sampling was used to select 104 patients with avascular necrosis of the femoral head who were treated in the First Affiliated Hospital of Zhengzhou University from September 2019 to October 2021 and underwent artificial hip replacement. The patients were divided into control group and observation group according to the random number table method, with 52 cases in each group. The control group was given routine nursing, and the observation group was given nurse-patient cooperative rehabilitation model based on the concept of rapid recovery. The Visual Analogue Score and Harris Hip Score were compared between the two groups before and after the intervention.Results:Pain scores of the observation group were lower than those of the control group five and ten days after operation and one month after discharge, and the differences were statistically significant ( P<0.05) . After intervention, the joint pain, functional changes, deformity and joint range of motion of the observation group were better than those of the control group, and the differences were statistically significant ( P<0.05) . Conclusions:The nurse-patient cooperative rehabilitation model based on the concept of rapid recovery for patients with avascular necrosis of the femoral head can improve the hip joint function of patients, alleviate pain and promote rehabilitation.
9.Effects and significance of continuous hemoperfusion on patients with diquat poisoning
Weizhan WANG ; Qian LIU ; Wenpin XU ; Tiezhen LIU ; Baoyue ZHU ; Hongna QI ; Qingmian XIAO ; Pu WANG ; Yaqin LI
Chinese Critical Care Medicine 2022;34(12):1320-1324
Objective:To investigate the effect of continuous hemoperfusion (HP) on the levels of soluble CD14 isoform (sCD14-st) and neutrophil gelatinase-associated lipocalin (NGAL) on patients with diquat (DQ) poisoning and its significance.Methods:A total of 86 patients with acute DQ poisoning admitted to the department of emergency medicine, Harrison International Peace Hospital Affiliated to Hebei Medical University from May 2018 to August 2021 were enrolled and divided into the intermittent HP group (40 cases) and the continuous HP group (46 cases) according to the random number table method. All patients received basic treatment and continuous veno-venous hemofiltration (CVVH) within 24 hours after admission. On this basis, the intermittent HP group received HP treatment within 2 hours, lasting 2 hours each time for every 8 hours, 3 times in all; the continuous HP group received continued HP treatment until there was no DQ component in urine samples. Serum NGAL levels were detected in all patients before treatment and at 3 hours, 12 hours, 24 hours, 2 days, 3 days, 5 days, and 7 days after treatment. At the same time, serum sCD14-st, blood lactate (Lac), arterial partial pressure of oxygen (PaO 2), serum creatinine (SCr), MB isoenzyme of creatine kinase (CK-MB) and interleukin-18 (IL-18) levels were detected before treatment and at 24 hours, 3 days, and 7 days after treatment. Kaplan-Meier survival curve was drawn to analyze the 28-day survival of patients. Results:Before treatment, there was no significant difference in serum NGAL, sCD14-st, Lac, PaO 2, SCr, CK-MB and IL-18 levels between the two groups. With the prolongation of treatment, the serum levels of NGAL, sCD14-st, Lac, SCr, CK-MB and IL-18 in the intermittent HP group increased at first and then decreased. Serum levels of NGAL, sCD14-st, CK-MB and IL-18 reached their peaks at 24 hours after treatment, and the Lac and SCr levels reached their peaks at 3 days after treatment. In addition, the levels of the above indexes at each time point in the continuous HP group were all significantly lower than those in the intermittent HP group [after 24 hours of treatment: NGAL (μg/L) was 345.90±30.75 vs. 404.24±38.79, sCD14-st (ng/L) was 1 941.88±298.02 vs. 2 656.35±347.93, CK-MB (U/L) was 30.67±9.11 vs. 43.28±8.06, IL-18 (ng/L) was 139.49±16.29 vs. 177.98±27.85; 3 days of treatment: Lac (mmol/L) was 2.98±0.26 vs. 3.72±0.49, SCr (μmol/L) was 125.01±24.24 vs. 156.74±28.88; all P < 0.05]. However, there was no significant difference in PaO 2 levels between the two groups at each time point after treatment. The Kaplan-Meier survival curve showed that the 28-day mortality of patients in the continuous HP group was significantly lower than that in the intermittent HP group [26.09% (12/46) vs. 52.50% (21/40); Log-Rank test: χ2 = 7.288, P = 0.007]. Conclusion:Continuous HP could effectively reduce serum sCD14-st, NGAL levels and 28-day mortality in patients with DQ poisoning, with good curative effect.
10.Relationship between adjuvant radiotherapy dose and pathologic complete response in patients with locally advanced esophageal squamous cell cancer
Xiaoxiao ZENG ; Hongna SUN ; Hao WEI ; Yong XU ; Xiaojuan ZHOU ; Zhenyu DING ; Youling GONG ; Jin WANG ; Lin ZHOU ; You LU ; Yong YUAN ; Yang HU ; Yongmei LIU
Chinese Journal of Radiation Oncology 2020;29(8):644-648
Objective:To investigate the relationship between the dose of preoperative neoadjuvant radiotherapy and the pathologic complete response (pCR) rate in patients with locally advanced squamous cell esophageal cancer (ESCC).Methods:Clinical data of 116 patients with ESCC who received neoadjuvant chemoradiotherapy followed by esophagectomy in our cancer center from July 2017 to December 2019 were retrospectively analyzed. The radiation doses were divided into 2 ranges based on Grays (Gy) received: 40-45 Gy and 45 Gy or more.Results:The overall pCR rate was 38. 8%(45/116). pCR was observed in 35 out of 80(44%) patients treated with 40-45 Gy and 10 of 36(28%) patients treated with 45 Gy or more. The pCR rate did not significantly differ between two groups [(40-45 Gy) vs.( ≥ 45 Gy), P=0.105)]. Conclusions:Preoperative neoadjuvant radiotherapy with a higher dose (≥ 45 Gy) fails to increase the pCR rate in patients with locally advanced ESCC. Prospective randomized trials are required to determine the optimal dose of preoperative adjuvant radiotherapy.

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