1.Mechanism of Qizhu Kang'ai Prescription for Inhibiting Proliferation of Hepatocellular Carcinoma by Regulating Tumor Metabolic Reprogramming via PCK1/Akt/p21 Signal Axis
Xin ZHONG ; Rui HU ; Jing LI ; Lanfen PENG ; Xingning LIU ; Qi HUANG ; Jialing SUN ; Xinfeng SUN ; Jianping CHEN ; Benqiang CAI ; Xiaozhou ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(3):26-36
ObjectiveTo study the effect of Qizhu Kang'ai prescription (QZAP) on the gluconeogenesis enzyme phosphoenolpyruvate carboxykinase 1 (PCK1) in the liver of mouse model of liver cancer induced by diethylnitrosamine (DEN) combined with carbon tetrachloride (CCl4) and Huh7 cells of human liver cancer, so as to explore the mechanism on regulating metabolic reprogramming and inhibiting cell proliferation of liver cancer cells. MethodDEN combined with CCl4 was used to construct a mouse model of liver cancer via intraperitoneal injection. A normal group, a model group, and a QZAP group were set up, in which QZAP (3.51 g·kg-1) or an equal volume of normal saline was administered daily by gavage, respectively. Serum and liver samples were collected after eight weeks of intervention. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (γ-GT), and alpha-fetoprotein (AFP) in mice were detected to evaluate liver function changes of mice in each group. Hematoxylin-eosin (HE) staining and Sirius red staining were used to observe pathological changes in liver tissue. In the cell experiment, Huh7 cells were divided into blank group, QZAP low, medium, and high dose groups and/or PCK1 inhibitor (SKF-34288 hydrochloride) group, and Sorafenib group. The corresponding drug-containing serum and drug treatment were given, respectively. Cell counting kit-8 (CCK-8) method, colony formation experiment, Edu fluorescent labeling detection, intracellular adenosine triphosphate (ATP) content detection, and cell cycle flow cytometry detection were used to evaluate the proliferation ability, energy metabolism changes, and change in the cell cycle of Huh7 cells in each group. Western blot was used to detect the protein expression levels of PCK1, serine/threonine kinase (Akt), phosphorylated Akt (p-Akt), and cell cycle-dependent protein kinase inhibitor 1A (p21). ResultCompared with the model group, the pathological changes such as cell atypia, necrosis, and collagen fiber deposition in liver cancer tissue of mice in the QZAP group were alleviated, and the number of liver tumors was reduced (P<0.01). The serum ALT, AST, γ-GT, and AFP levels were reduced (P<0.01). At the cell level, compared with the blank group, low, medium, and high-dose groups of QZAP-containing serum and the Sorafenib group could significantly reduce the survival rate of Huh7 cells (P<0.01) and the number of positive cells with Edu labeling (P<0.01) and inhibit clonal proliferation ability (P<0.01). The QZAP groups could also reduce the intracellular ATP content (P<0.05) and increase the distribution ratio of the G0/G1 phase of the cell cycle (P<0.05) in a dose-dependent manner. Compared with the model group and blank group, PCK1 and p21 protein levels of mouse liver cancer tissue and Huh7 cells in the QZAP groups were significantly reduced (P<0.05,P<0.01), and the p-Akt protein level was significantly increased (P<0.01). Compared with the blank group, the ATP content and cell survival rate of Huh7 cells in the SKF-34288 hydrochloride group were significantly increased (P<0.05), but there was no statistical difference in the ratio of Edu-positive cells and the proportion of G0/G1 phase distribution. Compared with the SKF-34288 hydrochloride group, the QZAP combined with the SKF-34288 hydrochloride group significantly reduced the ATP content, cell survival rate, and Edu-positive cell ratio of Huh7 cells (P<0.05) and significantly increased the G0/G1 phase distribution proportion (P<0.05). ConclusionQZAP may induce the metabolic reprogramming of liver cancer cells by activating PCK1 to promote Akt/p21-mediated tumor suppression, thereby exerting an anti-hepatocellular carcinoma proliferation mechanism.
2.Comparative Study on Flexible Ureteroscope Guided Peritoneal Dialysis Catheter Placement
Xiaozhou HAN ; Cheng ZHAO ; Jin QIU ; Jianxin LIU ; Shan LIN ; Yong ZHANG ; Changhai TIAN ; Wang LIU ; Huajun HU
Chinese Journal of Minimally Invasive Surgery 2024;24(1):29-33
Objective To explore the feasibility of peritoneal dialysis catheter placement assisted by flexible ureteroscope.Methods A retrospective analysis was conducted on clinical data of 54 cases of end-stage renal disease receiving peritoneal dialysis catheter placement from May 2019 to March 2023.The placement method was chosen by the patient.In the conventional group,23 cases were guided by a metal guide wire for insertion of the peritoneal dialysis catheter,while in the flexible ureteroscope group,31 cases were guided by flexible ureteroscope instead of guide wire for insertion of the peritoneal dialysis catheter.The success rate of catheterization,surgical time,use of postoperative analgesic,complications related to peritoneal dialysis catheter,and postoperative creatinine decrease were compared between the two groups.Results The catheter placement was successfully performed in both groups.The total incidence of complications related to peritoneal dialysis catheter in the flexible ureteroscope group was lower than that in the conventional group[6.5%(2/31)vs.30.4%(7/23),χ2 =3.878,P =0.049].Between the conventional group and the flexible ureteroscope group,there were no statistically significant differences in the surgical time,postoperative analgesic usage,and the decrease of creatinine at 2 weeks after surgery(P>0.05).The median postoperative follow-up period was10 months(range,3-24 months)in the two groups,and there were no complications such as peritoneal leakage,intestinal perforation,or intraperitoneal bleeding.Conclusion The placement of peritoneal dialysis catheter guided by the flexible ureteroscope instead of metal guide wire is a safe,visible,and accurate method,which can reduce complications related to peritoneal dialysis catheter,and detect and manage comorbidities in the abdominal cavity.
3.Assessment of dynamic cerebral autoregulation in pilots after acute positive acceleration exposure
Yanchun YOU ; Minghao YANG ; Xiao ZHANG ; Jinjin LIU ; Xiaozhou FAN ; Siguo SUN ; Xi LIU
Chinese Journal of Ultrasonography 2024;33(3):242-246
Objective:To explore the changes of dynamic cerebral autoregulation ability in pilots exposed to acute positive acceleration(+ Gz) by transcranial Doppler combined with beat-to-beat blood pressure.Methods:A total of 26 pilots enrolled in the + 8Gz manned centrifuge trial at the Air Force Medical Center, Air Force Medical University from June to October 2022 were prospectively included. Blood pressure and heart rate were monitored in the resting state before the trial and within 5 min after centrifugation. Transcranial Doppler combined with noninvasive continuous beat-to-beat blood pressure monitor were used to detect bilateral middle cerebral artery blood flow velocity and beat-to-beat pulse pressure respectively. The transfer function analysis was applied to derive the parameters of cerebral blood flow autoregulation in each frequency band from 0.02 to 0.50 Hz, and the phase, gain and coherence were calculated. The above parameters were compared between resting state and after acute + 8Gz positive acceleration exposure.Results:Compared with the resting state, in all of the 26 pilots after acute + 8Gz positive acceleration exposure, the systolic and diastolic blood pressure and heart rate increased significantly ( P<0.001), the phase significantly increased and the gain significantly decreased in the ultra-low frequency band (0.02-0.07 Hz) ( P<0.05); whereas there were no statistical differences of gain and phase in the low frequency band (0.07-0.20 Hz) and the high frequency band (0.20-0.50 Hz) (all P>0.05). Conclusions:Transcranial Doppler combined with beat-to-beat pulse pressure can be used for the assessment of changes in immediate dynamic cerebral autoregulation after acute + Gz exposure, and transfer function analysis of ultra-low frequency band parameters is suitable for this type of evaluation.
4.Study on quality evaluation of Buddleja officinalis from different habitats based on HPLC fingerprint and content determination
Cuijie WEI ; Xiaoxia LIU ; Zhiwen DUAN ; Yongwei FENG ; Xiaozhou JIA ; Yueyi LIANG ; Xiangdong CHEN ; Dongmei SUN ; Zhenyu LI
International Journal of Traditional Chinese Medicine 2024;46(2):215-221
Objective:To establish UPLC fingerprint method and 2 contents determination methods of Buddleja officinalis; To provide a reference for improving the quality control standard and evaluation of Buddleja officinalis from different habitats.Methods:UPLC method was used to establish the fingerprints of 17 batches of Buddleja officinalis. The similarity evaluation, clustering analysis, principal component analysis and orthogonal partial least squares discriminant analysis were used to compare the quality differences of Buddleja officinalis from different habitats. The contents of acteoside and linarin in Buddleja officinalis were determined.Results:There were 12 common peaks in UPLC fingerprints of Buddleja officinalis, six of which were identified as echinacoside, acteoside, cynaroside, isoacteoside, linarin, and apigenin. The fingerprint similarity of 17 batches of Buddleja officinalis was more than 0.9; Buddleja officinalis from different habitats were classified into 2 groups. Five differential markers were determined by OPLS-DA analysis. The order of significance was acteoside > peak 3 > echinacoside > isoacteoside > linarin. Edgeworthia chrysantha was identified by the method of fingerprint as counterfeit. The results of content determination showed that the content of Buddleja officinalis in Hubei and Sichuan was the high and stable.Conclusion:The method can effectively analyze the differences of Buddleja officinalis from different habitats, and provide reference for the quality control of Buddleja officinalis.
5.Long-term results of patent foramen ovale occlusion with the Pansy ? biodegradable occluder: a single-center clinical trial with 36-month follow-up
Ziang LI ; Xiaozhou ZHENG ; Qiang MIAO ; Yinsheng LEI ; Minghua WANG ; Xiankun LIU ; Zhigang GUO
Chinese Journal of Thoracic and Cardiovascular Surgery 2024;40(11):664-671
Objective:To test the feasibility, efficacy and safety of percutaneous patent foramen ovale(PFO) closure utilizing the Pansy biodegradable occluder(PBO) at 1-, 3-, 6-, 12-, 24-, and 36-month follow-up.Methods:In this single-center prospective clinical study, we enrolled 15 patients with PFO eligible for closure, all treated with the PBO, with device sizes ranging 24-34 mm. All clinical data were recorded in a 36-month follow-up period. Patients were summoned to the hospital in the 1, 3, 6, 12, 24, and 36 months after closure for transthoracic echocardiography(TTE), or transesophageal echocardiography(TEE), contrast transcranial doppler(cTCD) or contrast transthoracic echocardiography(cTTE), and a routine fasting blood sample.Results:The mean age was 27-68(44.0±16.4) years old. Indications for closure were cryptogenic stroke in 6 patients and migraine in 9 patients. Procedures were technically successful in 100%(15/15), in which course TTE showed that the position and shape of occluders were satisfactory. Small residual shunt was found by TTE in 2 patients with ASA in 1 month and 6 months after closure, respectively. 1 patient with cryptogenic stroke had another recurrent stroke 8 months after closure. At 12-month follow-up, 11 cases were closure. At 36-month follow-up, 13 cases were closure. 12 patients without atrial septal aneurysm(ASA) were closure. 1 patients with ASA was complete closure. No device-related complications occurred during the follow-up.Conclusion:PBO has good biocompatibility and suitable degradation time. A high technical success rate and closure rate can be achieved in those patients without ASA. Percutaneous closure of PFO using PBO is feasible, effective, and safe.
6.Medical equipment management practice in the establishment of a tertiary-A occupational disease specialized hospital
Meixia WANG ; Ruizhu FANG ; Diexian ZHONG ; Xu LIANG ; Liushan XIONG ; Shencheng HUANG ; Liping LIU ; Xiaozhou SU ; Hailin LIAO
China Occupational Medicine 2024;51(6):682-687
Passing the hospital grading evaluation, establishing a tertiary-A specialized hospital for occupational diseases, enhancing hospital's internal quality and sustainable development, and continuously improving medical service quality are important measures to promote the high-quality development of hospitals. The evaluation standards for occupational disease specialized tertiary-A hospital require standardized, scientific, and sustainable management of medical equipment. Guangdong Province Hospital for Occupational Disease Prevention and Treatment is the first tertiary-A hospital for occupational diseases specialized in Guangdong Province. Relative regulation on medical equipment management was systematically reviewed based on the requirement of tertiary-A specialized hospital for occupational diseases during hospital grading evaluation process. Building and completing the medical equipment management system, standardizing and strengthening government procurement management, completing the configuration management and safety management of large-scale medical equipment, strengthening the effectiveness analysis and evaluation of large equipment, enhancing training on medical equipment usage, establishing emergency allocation systems for first-aid and life support medical equipment, and forming a medical equipment quality and safety management team is the measure to systematically improve and implement each item in various regulation for the full lifecycle management of medical equipment. It provides vital support in passing the tertiary-A hospital evaluation for hospitals. During the hospital grading evaluation process, each issue identified in medical equipment management was addressed and improved. This process continuously enhanced the hospital's medical equipment management level, ensured the safe and effective use of medical equipment, and improved the quality of medical services, laying a solid foundation for the hospital to become a high level specialized medical institution for occupational diseases.
7.High preoperative neutrophile-lymphocyte ratio predicts poor prognosis of patients undergoing radical cystectomy for nonurothelial carcinoma of the bladder
Shuai LIU ; Xiaozhou ZHOU ; Guangjie DUAN ; Yuan LIU ; Peng HE ; Lang LANG ; Zhiwen CHEN
Journal of Modern Urology 2023;28(11):964-969
【Objective】 To investigate the predictive value of high preoperative neutrophile-lymphocyte ratio (NLR) for the prognosis of nonurothelial carcinoma of the bladder (NUBC) after radical cystectomy (RC). 【Methods】 Clinical and follow-up data of NUBC patients undergoing RC during Jan.2005 and Dec.2020 were collected. The optimal cut-off value of NLR was determined with the receiver operating characteristic (ROC) curve. The survival curve was drawn with Kaplan-Meier method to compare the differences in cancer specific survival (CSS) and overall survival (OS) between the high-NLR and low-NLR groups. The independent risk factors of CSS and OS were screened with Cox proportional hazard regression model. 【Results】 Of the 62 eligible cases,34 (54.8%) were diagnosed with adenocarcinoma,17 (27.4%) with squamous cell carcinoma, 6 (9.7%) with small cell carcinoma and 5 (8.1%) with sarcoma. Kaplan-Meier analysis results showed high NLR was associated with poor CSS (P=0.001) and OS (P<0.001). Cox regression results indicated that high NLR (HR=2.42, 95%CI: 1.12-5.23, P=0.025) and advanced pathologic tumor stage (HR=3.21, 95%CI:1.53-6.74,P=0.002) were independent risk factors of unfavorable CSS. Similarly, high NLR (HR=2.75, 95%CI: 1.35-5.56, P=0.005) and advanced pathologic tumor stage (HR=2.81, 95%CI:1.43-5.57, P=0.003) were independent risk factors of unfavorable OS. 【Conclusion】 As an independent risk factor of unfavorable CSS and OS in NUBC patients undergoing RC, high preoperative NLR is of great value in the prediction of long-term prognosis and may help to optimize individualized treatment.
8.Clinical characteristics of acute renal infarction: an analysis of 15 cases
Yinyin XIE ; Zhanwu LI ; Xiaozhou WANG ; Lei JIANG ; Qiang LIU ; Hao QIN ; Fangjun YANG
Chinese Journal of General Practitioners 2023;22(7):728-731
Clinical data of 15 patients diagnosed with acute renal infarction (ARI) in Affiliated Zhongshan Hospital of Dalian University from Jan 2011 to Dec 2021 were retrospectively analyzed. Of the included 15 patients, there were 14 cases of cardiac origin and 1 case of antiphospholipid syndrome. We found that there were 12 cases of atrial fibrillation, 2 cases of atrial premature beats, 12 cases of elevated level of D-dimer, 15 cases of elevated level of LDH, 11 cases of positive urine occult blood and positive urine protein. Among the 15 patients, catheter-directed thrombolysis was performed in 4 cases, of which 3 cases were revascularized successfully, intravenous thrombolysis in 2 cases and alone anticoagulation therapy in 9 cases. It is suggested that CECT or CTA can assist the early diagnosis of ARI especially in patients with acute onset and persistent abdominal pain with high risk factors of thromboembolism, high levels of LDH, microscopic hematuria and/or proteinuria. Despite prolonged embolic ischemia, try to reconstruct blood flow to save the kidney as much as possible. Late standardized anticoagulant therapy is of critical importance to prevent recurrent embolic episodes.
9.Ultrasonographic evaluation of cerebrovascular reactivity in flight crew after simulated acute altitude hypoxia
Weiwei YIN ; Yubin ZHOU ; Hua GUO ; Hongyu CHENG ; Manni DING ; Xiaozhou FAN ; Jia WANG ; Xi LIU
Chinese Journal of Ultrasonography 2022;31(1):25-29
Objective:To monitor the cerebral vascular blood flow parameters in the early stage of simulated acute exposure to high altitude hypoxia by transcranial color Doppler (TCCD), and to evaluate the change trend of cerebral hemodynamics and cerebrovascular reactivity.Methods:Sixty-four healthy volunteers were selected to observe the changes of peak systolic flow velocity(Vs), end diastolic flow velocity(Vd), mean flow velocity(Vm), resistance index (RI) and pulsatility index (PI) of middle cerebral artery (MCA) 30 minutes after they quickly entered the simulated altitude of 4 500 meters. Combined with breath holding test, breath holding index (BHI) was used to evaluate cerebrovascular reactivity (CVR), and subjects were divided into ≤30 years old group and >30 years old group, and the changes of CVR after hypoxia of the two groups were compared.Results:In the early stage of hypoxic environment, compared with baseline, SpO 2 decreased, heart rate increased, and blood flow velocity of middle cerebral artery(Vs, Vd, Vm) increased significantly, BHI showed a decreasing trend (all P<0.01). After hypoxia, the BHI rate of change in >30 years old was lower than that of the subjects ≤30 years old ( P<0.05). After breath holding, cerebral blood flow velocity increased significantly, PI and RI decreased significantly (all P<0.01). Conclusions:Cerebral blood flow is very sensitive to hypoxia. The application of TCCD technology can evaluate the trend of cerebral blood flow dynamics and cerebrovascular reserve capacity in real time and accurately, which is helpful to provide objective basis and research basis for the prevention and treatment of high altitude hypoxia.
10.Efficacy of Qingfei oral liquid for idiopathic pulmonary fibrosis in rats and related network pharmacology study.
Yiwen ZHANG ; Kongsheng SHENG ; Feifeng SONG ; Zongfu PAN ; Xiaozhou ZOU ; Yujia LIU ; Ping HUANG
Journal of Zhejiang University. Medical sciences 2022;51(1):53-61
To investigate the therapeutic effect and mechanism of Qingfei oral liquid in idiopathic pulmonary fibrosis. Seventy-two male SD rats were divided into control group, model group, pirofenidone group and Qingfei group with 18 animals in each group. The idiopathic pulmonary fibrosis was induced in last three groups by intratracheal injection of bleomycin; pirofenidone group was given oral administration of pirofenidone b.i.d for 21 d, and Qingfei group was given Qingfei oral liquid 3.6 mL/kg q.d for Lung tissues were obtained for HE staining, Masson staining and transforming growth factor (TGF)-β immunohistochemical staining. Superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) were detected in tissue homogenates. The BATMAN-TCM database was used to retrieve the chemical components and their corresponding targets of Qingfei oral solution by network pharmacology method, and then the component-target-disease network diagram was constructed. Finally, the pathway enrichment analysis was carried out to explore the molecular mechanism of Qingfei oral liquid against idiopathic fibrosis. Histopathology results showed that Qingfei oral liquid had a similar relieving effect on pulmonary fibrosis as the positive drug pirfenidone; TGF-β secretion had a significant reduction in lung tissues of Qingfei group; and Qingfei oral liquid had better regulatory effect on SOD, MDA and GSH than pirfenidone. The results of component-target-disease network and pathway enrichment analysis showed that the related molecular pathways were concentrated in inflammation, extracellular matrix and cytokines. Qingfei oral liquid has a good therapeutic effect on idiopathic pulmonary fibrosis in rats via regulation of inflammation, extracellular matrix and cytokines.
Animals
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Bleomycin/pharmacology*
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Cytokines
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Drugs, Chinese Herbal
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Glutathione
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Idiopathic Pulmonary Fibrosis/drug therapy*
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Inflammation
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Lung/pathology*
;
Male
;
Network Pharmacology
;
Rats
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Rats, Sprague-Dawley
;
Superoxide Dismutase/metabolism*
;
Transforming Growth Factor beta/pharmacology*

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