1.Effects of formononetin on the apoptosis of intestinal epithelial cells in rats with inflammatory bowel disease by regulating the Hippo/YAP signaling pathway
Dong XIE ; Yuanyuan LIU ; Zhengxiang LI ; Hengjie YUAN ; Xiaocang CAO
China Pharmacy 2024;35(13):1564-1569
OBJECTIVE To investigate the effects of formononetin (FMN) on the apoptosis of intestinal epithelial cells in inflammatory bowel disease (IBD) rats and its possible mechanism. METHODS IBD rat model was constructed by using trinitrobenzene sulfonic acid (TNBS) induction. Forty-eight rats with successful modeling were divided into model group (normal saline), low-dose and high-dose FMN groups (20 and 40 mg/kg FMN), and high-dose FMN+YAP inhibitor Verteporfin (VTPF) group (40 mg/kg FMN+10 mg/kg VTPF), with 12 rats in each group. Another 12 rats were set as the normal group (normal saline). They were given drug/normal saline, once a day, for 7 consecutive days. After the last administration, the disease activity index (DAI) of rats was calculated, and the colon length of rats in each group was measured. The pathological changes in the colon tissue of rats were observed. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-10 in serum were detected, and the apoptosis of intestinal epithelial cells was detected. The expressions of Yes associated protein (YAP), cleaved cysteine-containing aspartate proteolytic enzyme 3 (cleaved-caspase-3), B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) were detected in colon tissue of rats. RESULTS Compared with the normal group, DAI score, the levels of TNF-α and IL- 6, the apoptotic rate of intestinal epithelial cells, and the expressions of cleaved-caspase-3 and Bax protein in the model group were increased greatly (P<0.05); the length of the colon was greatly decreased (P<0.05), and the serum level of IL-10 and the protein expressions of YAP and Bcl-2 were greatly reduced (P<0.05). The cell morphology of colon tissue was abnormal, with disordered arrangement and inflammatory cell infiltration. Compared with IBD group, the above indexes of rats were improved significantly in low-dose and high-dose FMN groups (P<0.05), in dose-dependent manner (P<0.05). VTPF significantly alleviated the effects of FMN on the above indexes of IBD rats (P<0.05). CONCLUSIONS FMN may promote the expression of YAP by inhibiting the Hippo/YAP signaling pathway, thereby inhibiting apoptosis of intestinal epithelial cells in IBD rats.
2.Prognosis and risk factors of Coronavirus Disease-19 associated acute pancreatitis
Jianfeng TU ; Zhaowang TAN ; Yunyun MAO ; Yueliang ZHENG ; Qian LI ; Sheng’ang ZHOU ; Hengjie LI ; Wenwei CAI
Chinese Journal of Emergency Medicine 2024;33(9):1291-1296
Objective:To analyze the clinical features, prognosis and risk factors of SARS-CoV-2 associated acute pancreatitis (SAAP), and provide a basis for early prevention and treatment of SAAP.Methods:Patients with coronavirus disease 19 infection (COVID-19) admitted to Zhejiang Provincial People's Hospital from December 1, 2022 to January 31, 2023 were retrospectively analyzed. Clinical characteristics such as age, gender and other data were recorded, and the indexes of blood routine, liver and kidney function, inflammatory factor, coagulation function, blood gas analysis, immunoglobulin and complement were collected after admission. Patients were divided into pancreatic injury group and non-pancreatic injury group according to the level of serum amylase/lipase. The difference of prognosis and related hematological parameters between the two groups was compared. Multifactorial logistic regression equation was constructed to analyze the risk factors of SAAP.Results:A total of 2 101 patients with COVID-19 who met the criteria were included, including 298 patients in the pancreatic injury group and 1 803 patients in the non-pancreatic injury group. 17 cases (5.7%) in the pancreatic injury group met the diagnostic criteria for AP. The age, male percentage and mortality rate of the pancreatic injury group were all significantly higher than those of the non-pancreatic injury group (all P<0.05). In the pancreatic injury group, white blood cell count, neutrophil-to-lymphocyte ratio, C-reactive protein (CRP), calcitoninogen, erythrocyte sedimentation rate, inflammatory cytokines, tumour necrosis factor, liver and kidney functions, coagulation (D-dimer and plasma fibrinogen degradation products), and lactate level were significantly higher than those in the non-pancreatic injury group (all P<0.05). Serum complement C3, albumin, albumin globule ratio and arterial oxygenation index were lower in the pancreatic injury group (all P<0.05). Multifactorial logistic regression analysis showed that gender, age, CRP, calcitoninogen, total bilirubin, creatinine, PaO 2, PaO 2/FiO 2 and lactate were independent risk factors for the occurrence of pancreatic injury in patients with COVID-19 (all P<0.05). Conclusions:Inflammation-related markers, D-dimer and fibrinogen degradation products were significantly higher in COVID-19 patients comorbid with pancreatic injury than in the patients without pancreatic injury. The risk of SAAP was significantly higher in male patients of senior age. Sex, age, CRP, calcitoninogen, total bilirubin, creatinine, oxygenation index, and lactic acid were independent risk factors for the onset of pancreatic injury in COVID-19 patients.
3.Research on cognitive characteristics and influencing factors of CSF1R related diseasess
Duxin JI ; Jingying WU ; Xin CHENG ; Hengjie WANG ; Li CAO
Journal of Chinese Physician 2024;26(7):969-973
Objective:To analyze the characteristics and possible influencing factors of cognitive impairment in patients with CSF1R related diseases (CRD), and provide a basis for the diagnosis, evaluation, treatment, and prognosis of CRD.Methods:A retrospective analysis was conducted on CRD patients diagnosed at the Shanghai Sixth People′s Hospital from April 1, 2018 to May 1, 2024. Information such as gender, age of onset, family history, Montreal Cognitive Assessment (MoCA) score, Mini Mental State Examination (MMSE) score, imaging features, and CSF1R gene mutations were collected to analyze the phenotypic characteristics of CRD patients with different cognitive levels. Multiple linear regression was used to identify factors that may be related to CRD cognitive dysfunction.Results:A total of 40 patients were collected, including 22 males and 18 females. 42.5%(17/40) of the patients had a family history, with an onset age of (39.6±7.9)years and an overall median disease duration of 1.25(1.00, 2.00)years. The MMSE score was (17.90±7.89)points and the MoCA score was (15.16±7.76)points. All patients had frontal leukoencephalopathies and no cerebellar involvement. The cognitive impairment of patients was multidimensional, mainly characterized by orientation disorders, structural barriers attention and calculation disorders, visual spatial and executive dysfunction, delayed recall disorders, and language dysfunction. Patients with onset age ≥40 years old had poorer abstract ability. In addition, patients with a positive family history had poorer immediate memory and naming abilities, while those with ventricular dilation had poorer scores in MMSE total score, MoCA total score, orientation, delayed recall ability, and naming ability.Conclusions:CRD patients generally exhibit significant impairment in multiple cognitive domains, mainly characterized by deficits in orientation, structure attention, and computational abilities. Patients with early onset, long course of illness, positive family history, and ventricular enlargement are more likely to experience partial cognitive decline.
4.Analysis and evaluation of the application of polymyxin B in inpatients based on clinical guidelines and consensuses
Meng LI ; Longxi PENG ; Gaoshuang LAN ; Jie YU ; Zhengxiang LI ; Hengjie YUAN
China Pharmacy 2023;34(6):730-734
OBJECTIVE To evaluate the rationality of clinical application of polymyxin B in the inpatients of a third grade class A hospital,so as to provide evidence for the optimization of clinical scheme of the drug. METHODS A retrospective method was conducted on the electronic medical records of inpatients treated with Polymyxin B sulfate for injection from January 2020 to March 2022 to collect the basic information of patients, inpatient departments and time, infection diagnosis, results of pathogenic bacteria test, laboratory test indicators, usage and dosage, and combined medication,etc. Based on the drug instructions, according to relevant guidelines and consensus, the rationality, efficacy and safety of polymyxin B in inpatient were evaluated. RESULTS & CONCLUSIONS A total of 101 inpatients were included, respiratory system infection was the main cause (62.4%). All patients had received the etiological examination, and the pathogen with the highest detection rate was carbapenem‑resistant Acinetobacter baumannii (40.6%). One hundred patients were treated by intravenous drip, and 4 patients were treated by combination of aerosol inhalation or intrathecal injection; 99 patients were given the dose of 500 thousand units by continuous intravenous infusion, q12 h. Totally 51.5% of patients were treated for 7-14 days; and 77 patients were treated with other anti-Gram-negative drugs. There were unreasonable phenomena including too short time of medication (29.7%), no combination of medication (23.8%), and no indication of medication (17.8%). The clinical effective rate of 101 patients treated with polymyxin B was 49.5%, and 16 patients (15.8%) had acute kidney injury during the treatment. Clinical pharmacists should actively participate in the clinical treatment of polymyxin B, formulate individualized treatment plans according to the guidelines/consensus and in combination with the patient’s condition and infection status to improve the rationality of clinical medication.
5.Association between cancer fatalism and optimistic attitudes in colorectal cancer patients and the moderating effects
Hengjie JIA ; Mingwei TIAN ; Xiaozhe GU ; Jingyu ZHANG ; Shuhua LI ; Yun YANG
International Journal of Surgery 2023;50(4):252-258
Objective:To investigate the association between cancer fatalism and optimistic attitudes among colorectal cancer patients, and how the above linkage is moderated by the involvement of patients′ opinions, the family members′ opinions and the physicians′ opinions in treatment decision-making.Methods:A cross-sectional survey was conducted on 64 patients diagnosed with colorectal cancer and awaiting radical colorectal cancer surgery in the Department of General Surgery of Beijing Friendship Hospital Affiliated to Capital Medical University, from January 2021 to December 2021. There were 38 males and 26 females, aged (61.2±13.0) years from 30 to 84 years. Cancer fatalism, optimism attitudes, and the involvement of patients′ opinions, the family members′ opinions and the physicians′ opinions in treatment decision-making were assessed. The patients′ cancer fatalism beliefs were measured by the " Chance" subscale of the Form C of the Multidimensional Health Locus of Control (MHLC-C), optimism attitudes were assessed by the Chinese version of the revised Life Orientation Test (CLOT-R), and the influence of patients′, family members′, and physicians′ opinions in the medical decision-making process was measured by a self-designed single factor scale. Measurement data of normal distribution were expressed as mean±standard deviation ( ± s). Measurement data of skewed distribution were expressed as M( Q1, Q3). Spearman correlation analysis and Chi-square test was used to examine the association between the main outcome variable (patients′ optimistic attitudes) and demographic and clinical characteristics. Interaction was examined by hierarchical linear regression analysis combined with simple slope tests. Results:Cancer fatalism was negatively associated with patients′ optimistic attitudes ( r=-0.35, P<0.01). Optimistic attitude of patients was significantly and negatively correlated with the influence of family members′ opinions on medical decision-making ( r=-0.25, P<0.05). There were significant positive correlations between the influence of patients′ and family members′ opinions ( r=0.50, P<0.01), family members′ and physicians′ opinions ( r=0.67, P<0.01), and physicians′ and patients′ opinions ( r=0.38, P<0.01) in medical decision making. Hierarchical linear regression analysis showed a negative association between cancer fatalism and optimism ( β=-0.32, P=0.01). This association was further moderated by the involvement of family members′ opinions ( β=-0.56, P<0.01) and the involvement of physicians′ opinions ( β=-0.36, P=0.04) in medical decision-making. Simple slope tests revealed that the negative impact of fatalistic attitudes on patients′ optimism attitudes may be potentiated when family members′ opinions have high influence on medical decision-making, while the negative impact may be buffered to some extent when physicians′ opinions have high influence on medical decision-making. Conclusions:Cancer fatalism had a negative effect on patients′ optimism. The high influence of physicians in treatment decision-making buffered the negative effect of cancer fatalism on optimism; the high influence of family members in treatment decision-making potentiated the negative effect of cancer fatalism on optimism. In the process of doctor-patient communication and shared decision-making, for patients with strong fatalistic attitudes, consideration should be given to appropriately increasing direct informational communication between physicians and patients and reducing excessive family intervention in medical decision-making, so as to enhance patients′ autonomy for treatment, promote optimism, and reduce the negative effects of cancer fatalism.
6.Analysis of Non-target Proteins in Human Albumin and Human Immunoglobulin by UHPLC-LTQ- Orbitrap-MS
ZHANG Hengjie ; TANG Yao ; WANG Juexiao ; JIANG Jiaxing ; LONG Lijuan ; MA Jing ; WANG Shuqiao ; LI Yan ; YANG Lei
Chinese Journal of Modern Applied Pharmacy 2023;40(19):2713-2720
OBJECTIVE To analyze and identify non-target proteins in human albumin and human immunoglobulin by ultra high performance liquid chromatography tandem linear ion trap orbitrap mass spectrometry. METHODS The extract was separated on a ACQUITY UPLC peptide BEH C18(300Å, 1.7 μm, 2.1 mm×100 mm) column and the gradient elution was performed with mobile phase consisting of 0.1% formic acid aqueous solution-0.1% formic acid acetonitrile. The analytes were detected in Full MS/dd-MS2(TopN). RESULTS A total of 52 non-target proteins were identified from human albumin and human immunoglobulin. Among them, 25 non-target proteins were identified in human albumin samples, and 27 non-target proteins were identified in human immunoglobulin samples. CONCLUSION The established qualitative method can rapidly, accurately and systematically identify various proteins in human albumin and human immunoglobulin. The results provide reference for the quality control of the preparation as well as its further clinical application.
7.Ischemic myocardial contracture occurred in early stage of asphyxia-induced cardiac arrest in rats
Hengjie LI ; Hui MAO ; Yong NAN ; Nannan HAN ; Wenwei CAI
Chinese Journal of Emergency Medicine 2020;29(8):1078-1081
Objective:To investigate the characteristics of ischemic myocardial contracture after asphyxia-induced cardiac arrest (CA).Methods:Asphyxia and ventricular fibrillation (VF) induced cardiac arrest model was established. Thirty-one male Wistar rats were randomly(random number) assigned to the sham, asphyxia and VF groups. Electrocardiogram and blood pressure during CA stage were recorded. Arterial blood was drawn for blood gas analysis at 0 min after CA. The length and width of the heart were measured at 0,2,4,6 and 8 min after CA. The myocardial ATP contents were measured at 0 and 8 min after CA.Results:Compared with the VF group, the time of CA induction was longer in the asphyxia group[ (237±20 ) s vs (3±1) s, P<0.05]. At 0 min after CA, severe hypoxemia, carbon dioxide retention and acidosis had occurred in the asphyxia group, while these indexes in the VF group were basically normal. The length and width of the heart in the asphyxia group decreased gradually after CA, the myocardial contracture reached the limit around 6 min after CA, while the cardiac morphology of the VF group did not change significantly during the observation period of 8 min after CA. Myocardial ATP content in the asphyxia group decreased significantly at 0 min after CA ( P<0.05), while the difference between the VF group and the sham group was not statistically significant ( P>0.05). Conclusions:Myocardial contracture occurrs in the early stage of asphyxia CA, which may be related to ATP consumption in the asphyxia stage.
8.Efficacy and Safety of Rivaroxaban versus Low Molecular Weight Heparin in the Prevention of Venous Thromboembolism in Patients with Hip Fracture :A Meta-analysis
Liliang WANG ; Jin JIN ; Yang YANG ; Zhengxiang LI ; Hengjie YUAN
China Pharmacy 2019;30(1):120-124
OBJECTIVE: To systematically evaluate the efficacy and safety of rivaroxaban versus low molecular weight heparin in the prevention of venous thromboembolism (VTE) in patients with hip fractures, and to provide evidence-based reference for clinical application. METHODS: Retrieved from Cochrane library, PubMed, Embase, CNKI, VIP and Wanfang database, randomized controlled trials (RCTs) about rivaroxaban (test group) versus low molecular weight heparin (control group) in the prevention of VTE in patients with hip fracture were collected during database establishment to Jun. 2018. After data extraction and quality evaluation with Cochrane system evaluator manual 5.1.0, Meta-analysis was performed by using Rev Man 5.3 statistical software for the incidence of deep venous thrombosis (DVT), postoperative discharge, activated partial thromboplastin time (APTT), prothrombin time (PT) and the incidence of ADR. RESULTS: Totally 8 RCTs were included, involving 949 patients. Results of Meta-analysis showed that compared with low molecular weight heparin, rivaroxaban could significantly decreased the incidence of DVT [RR=0.55, 95%CI (0.36, 0.83), P=0.004]. There was no statistical significance in postoperative discharge [MD=-0.24, 95%CI (-5.27, 4.8), P=0.93], APTT [MD=0.56, 95%CI (-0.75, 1.86), P=0.40], PT [MD=0.04, 95%CI(-0.03, 0.11), P=0.25] or the incidence of ADR [RR=1.73,95%CI(0.15,20.48), P=0.66] between 2 groups. CONCLUSIONS: Rivaroxaban has a better preventive effect on VTE in patients with hip fracture than low molecular weight heparin, and has a similar safety as low molecular weight heparin.
9.The characteristics of myocardial injury in rats resuscitated from cardiac arrest
Hengjie LI ; Hui MAO ; Wenwei CAI ; Hongyan WEI ; Gang DAI ; Yuanzheng LU ; Bo LI ; Xiaoxing LIAO
Chinese Journal of Emergency Medicine 2019;28(1):25-29
Objective To investigate the characteristics of myocardial injury and its underlying mechanism in rats resuscitated from cardiac arrest. Methods Forty-two male Wistar rats were randomly(random number) assigned into the post-resuscitation (PR) 4 h, PR 24 h, PR 48 h, and sham groups. Ventricular fibrillation was induced by transcutaneous electrical epicardium stimulation and untreated for 6 min, followed by cardiopulmonary resuscitation (CPR). Myocardial function, glucose metabolism, myocardial ultrastructure, the status of mitochondrial permeability transition pore (MPTP) and mitochondrial membrane potential (MMP) were evaluated at different time points. Results Myocardial dysfunction was found at 4 h after restoration of spontaneous circulation (ROSC). The ejection fraction and cardiac output were decreased (all P<0.01), the diastole left ventricular posterior wall became thicker (P<0.01), and the end-diastolic volume was reduced (P<0.05). However, cardiac function was recovered almost completely at 48 h after ROSC. The PR 4 h group had a higher SUVmax, a more obvious decreased absorbance, and a lower MMP than the sham group (all P<0.01), but no statistically significant differences were noted between the PR 48 h group and the sham group (P>0.05). At 4 h and 24 h after ROSC, the mitochondria was swollen and the mitochondrial crista was sparse, but the myocardial ultrastructure was complete. Conclusions Post resuscitation myocardial dysfunction occurs after ROSC and the myocardial dysfunction is completely reversible at 48 h after ROSC, which may be related to the reversibility of myocardial injury and the gradual recovery of mitochondrial structure and function.
10.Sevoflurane reduces cerebral injuries in rats resuscitated from cardiac arrest through down regulating the expression of Bax and Bak
Hengjie LI ; Hui MAO ; Yong NAN ; Hongyan WEI ; Gang DAI ; Yan YANG ; Bo LI ; Xiaoxing LIAO
Chinese Journal of Emergency Medicine 2019;28(5):579-583
Objective To investigate the neuroprotective mechanism of sevoflurane in rats resuscitated from cardiac arrest (CA).Methods A ventricular fibrillation-induced CA model was established.Forty Wistar rats were randomly divided into the sham group,sevoflurane group and control group.Apoptosis-related proteins were measured by Western blot at 24 h after restoration of spontaneous circulation (ROSC).The status of mitochondrial permeability transition pore (MPTP) were measured using a spectrophotometer,and the mitochondrial membrane potential (MMP) were measured with JC-1 fluorescent probe.At 72 h after ROSC,the apoptotic index of neurons in hippocampal CA1 region was counted by TUNEL staining.Results The protein expression of Bax,Bak,cleaved-caspase 9,cleavedcaspase 3 and cytosolic cytochrome c were lower in the sevoflurane group (all P<0.05),the protein expression of Bcl-2 was higher in the sevoflurane group compared with the control group (P<0.05).The sevoflurane group had a less opening status of MPTP and a higher MMP compared with the control group (all P<0.05).The sevoflurane group had less apoptotic neurons compared with the control group (P<0.05).Conclusion By up-regulating the expression of Bcl-2,down-regulating Bax and Bak,sevoflurane could reduce the apoptosis of neurons and decrease the opening of MPTP,eventually reduce cerebral injuries.


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