1.Application of Carbon Nanoparticle-Manganese Dioxide Injection in Gastrointestinal Staining-Based Marking and Localization in Rats and Pigs
Wanlin CHEN ; Qingrui DONG ; Mengtao LI ; Nan LIN ; Hu ZHAO ; Zaizhong ZHANG ; Lingjun ZENG ; Pei LI ; Jin YANG ; Yu WANG ; Aiwen HUANG
Laboratory Animal and Comparative Medicine 2026;46(5):727-739
ObjectiveTo develop a carbon nanoparticle-manganese dioxide (CN-MnO2) injection integrating visually identifiable staining and magnetic resonance (MR) T1/T2 dual-modal imaging, and to systematically evaluate its physicochemical properties, critical quality attributes, biocompatibility, and efficacy for gastrointestinal marking and localization. MethodsCN-MnO2 was prepared using a mild liquid-phase in situ redox deposition strategy and characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential analysis, X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD). The pH of CN-MnO2 was directly measured using a pH meter. The osmolality pressure of CN-MnO2 was determined by the freezing point depression method. The bacterial endotoxin was detected using the gel-clot Limulus amebocyte lysate test, which did not rely on absorbance readings. The appearance of the CN-MnO2 injection solution stored at 4 ℃ under light shielding and sealed for 0, 5, and 10 days was observed, and its hydrated particle size, polydispersity index, zeta potential, and pH were also measured. With gadopentetate dimeglumine (Gd-DTPA) as the positive control, different concentration gradients were established, and T1 and T2 relaxation times were measured to construct concentration-dependent plots of the longitudinal and transverse relaxation rates (R1 and R2) and calculate the corresponding relaxivities (r1 and r2), compare relaxivity performance, and determine the working concentration for subsequent in vivo experiments. Cytocompatibility was assessed using the methyl thiazolyl tetrazolium (MTT) assay and live/dead staining. Sixteen male 6-week-old SD rats were randomly assigned to an experimental group and a control group (n=8 per group) and subcutaneously injected with CN-MnO2 injection at a total Mn concentration of 0.80 mmol/L or an equal volume of normal saline, respectively. Short-term in vivo safety was evaluated by regular body weight monitoring, hematoxylin-eosin (HE) staining of major organs, hematological and serum biochemical analyses, inflammatory cytokine detection, and inductively coupled plasma optical emission spectrometry (ICP-OES) analysis. Eight male 5–6-month-old Bama minipigs were randomly assigned to a CN-MnO2 group (n=6) and a carbon nanoparticle suspension injection (CNSI) group (n=2). CN-MnO2 injection or CNSI was injected subserosally into the stomach, small intestine, and colon. Within 5 min after each injection, the maximum staining diameter at each injection site was measured and recorded. MR T1WI/T2WI scans were performed on days 3 and 7 after injection to evaluate MR visualization at the injection sites. At the end of observation, the injection sites and major organs were collected for histopathological evaluation by hematoxylin-eosin staining. ResultsCN-MnO2 appeared as a black suspension, with no obvious aggregation or sedimentation after standing at room temperature (20-25 ℃) for 15 days. Its average hydrodynamic diameter was approximately (228.7±15.3) nm, the polydispersity index was 0.184±0.021, and the zeta potential was (-24.6±2.8) mV. XPS showed that CN-MnO2 was mainly composed of C, O, and Mn, with oxygen accounting for approximately 68.82%. The Mn 2p spectrum exhibited two characteristic peaks at 642.4 and 653.1 eV. XRD indicated that low-crystallinity δ-MnO2 was dispersed within the carbon matrix. The pH was 6.82±0.06, the osmolality was (298.4±6.7) mOsm/kg, and the bacterial endotoxin level was below the detection limit. In vitro MR imaging showed a clear concentration-dependent response, with r1 and r2 values of 9.6 L·mmol-1·s-1 and 17.2 L·mmol-1·s-1, respectively, indicating favorable T1/T2 contrast performance superior to that of Gd-DTPA. At 0.80 mmol/L, CN-MnO2 showed no obvious cytotoxicity in vitro. Short-term safety evaluation in SD rats revealed no obvious inflammatory response, impairment of liver or renal function, or abnormal manganese accumulation in major organs. In Bama minipigs, the mean staining diameters of the CN-MnO2 group in the stomach, small intestine, and colon were (0.65±0.12) cm, (0.61±0.11) cm, and (0.58±0.10) cm, respectively, with no significant difference among the three injection sites (P>0.05). The overall mean staining diameter was smaller in the CN-MnO2 group than in the CNSI group (P<0.05). MR examinations showed that the injection sites were identifiable on both day 3 and day 7, with stronger signals observed on day 3. At the end of observation, no obvious pathological abnormalities were observed at the injection sites or in major organs. ConclusionA CN-MnO2 injection with uniform particle size and stable physicochemical properties can be successfully prepared. This formulation integrates visible gastrointestinal staining with MR T1/T2 dual-modal imaging, providing a new strategy for preoperative gastrointestinal marking and localization as well as precise intraoperative resection.
2.Epidemiological Analysis of Pathogens in Acute Respiratory Infections During the 2023-2024 Autumn-Winter Season in Beijing:A Case Series of 5556 Patients at Peking Union Medical College Hospital
Yan CAO ; Yu CHEN ; Jie YI ; Lingjun KONG ; Ziyi WANG ; Rui ZHANG ; Qi YU ; Yiwei LIU ; Maimaiti MULATIJIANG ; Chenglin YANG ; Yujie SUN ; Yingchun XU ; Qiwen YANG ; Juan DU
Medical Journal of Peking Union Medical College Hospital 2025;16(3):680-686
Objective To analyze the epidemiological characteristics of acute respiratory infections(ARIs)during the autumn-winter season in Beijing,providing evidence for the prevention,control,diagnosis,and treatment of ARIs.Methods A convenience sampling method was employed,enrolling patients who visited Peking Union Medical College Hospital(PUMCH)between September 2023 and February 2024 due to ARIs.Na-sopharyngeal swabs were collected,and real-time fluorescence quantitative PCR was used to detect six common respiratory pathogens[influenza A virus(FluA),influenza B virus(FluB),human rhinovirus(HRV),Myco-plasma pneumoniae(MP),respiratory syncytial virus(RSV),and adenovirus(ADV)],as well as SARS-CoV-2 infection.The distribution patterns of pathogen infections were analyzed.Results A total of 5556 eligible patients were included.The overall positivity rate for the six common respiratory pathogens was 63.7%,with sin-gle-pathogen positivity at 54.0%,dual-pathogen positivity at 8.9%,and triple or more pathogen positivity at 0.7%.The predominant pathogens detected were FluA(16.1%)and RSV(15.7%),followed by ADV(11.1%),MP(11.1%),HRV(10.0%),and FluB(10.0%).No significant difference in overall pathogen positivity was observed between genders.However,significant differences were found between autumn and winter(x2=34.617,P<0.001)and among pediatric,young/middle-aged,and elderly patients(x2=422.38,P<0.001).Specifically,MP(x2=8.647,P=0.003),FluA(x2=131.932,P<0.001),and HRV(x2=174.199,P<0.001)exhibited significantly higher positivity rates in autumn than in winter,whereas FluB was more prevalent in winter(x2=287.894,P<0.001).In pediatric patients,MP,RSV,HRV,and ADV positivity rates were significantly higher than in young/middle-aged and elderly patients(all P<0.001),whereas FluB was more common in young/middle-aged patients(both P<0.001).The positivity rates of the six common respiratory pathogens significantly declined during the SARS-CoV-2 epidemic period,exhibiting an asynchronous seasonal pattern.Conclusions The prevalence of respiratory pathogens in Beijing is associated with age and season.Tar-geted preventive measures should be implemented in different seasons and for key populations.
3.Research Progress in Anti-tumor Mechanisms of Prunellae Spica and Its Active Components
Mengqi LI ; Yu SHI ; Shiyu YANG ; Jieyu LI ; Yu HU ; Wenxiu SUN ; Lingjun LI
Chinese Journal of Modern Applied Pharmacy 2024;41(5):716-726
As a common clinical Chinese medicine, Prunellae Spica has the effects of clearing liver-fire, improving eyesight, resolving massesand detumescence, and has strong anti-tumor effects against thyroid cancer, breast cancer, liver cancer and other cancers. Extracts of Prunellae Spica and its active components can play an anti-tumor role in a variety of ways, including cell apoptosis, inhibiting cell invasion and metastasis, inhibiting cell proliferation, inducing autophagy, anti tumor angiogenesis, reversing tumor multidrug resistance and regulating immune function, by regulating miRNA and Wnt/β-catenin, PI3/AKT, AMPK/mTOR/ULK1, RANKL/RANK/OPG and other signal pathways . In this paper, the anti-tumor mechanism of Prunellae Spica extract was reviewed, in order to provide reference for further research and application.
4.Advances on Chemical Constituents of Volatile Oil from Angelicae Sinensis Radix and Their Pharmacological Effect
Yu SHI ; Mengqi LI ; Shiyu YANG ; Yu HU ; Wenxiu SUN ; Lingjun LI
Chinese Journal of Modern Applied Pharmacy 2024;41(7):1006-1014
Angelicae Sinensis Radix, drived from a medicinal and edible plant Angelica sinensis, with the reputation of "nine Angelica recipes out of ten". The volatile oils from Angelicae Sinensis Radix was the main medicinal component of Angelicae Sinensis Radix, mainly including benzene phthalides, terpenoids and alkanes, its chemical composition was complex. Such factors as growth environment, concoction process, extraction methods and other factors all can trigger changes in volatile oil constituents and content from Angelicae Sinensis Radix. Angelicae Sinensis Radix essential oil has diverse pharmacological activities such as anti-hypotension, protection of ischemia-reperfusion injury, asthma, anti-inflammatory and anti-cancer, etc., implying its high clinical application value. This paper reviewed the literature on the volatile oil of Angelicae Sinensis Radix in the past ten years, the chemical components of Angelicae Sinensis Radix were sorted out and the factors affecting the chemical components were summarized, focusing on its anti-hypotensive, ischemia-reperfusion injury protection, asthma and other active effects, in order to provide reference for the further development and utilization of the volatile oil of Angelicae Sinensis Radix.
5.Recombinant Schistosoma japonicum cystatin alleviates acute liver injury in mice by inhibiting endoplasmic reticulum stress,inflammation and hepatocyte apoptosis
Lingjun LU ; Xiaodi YANG ; Huaping ZHANG ; Yuan LIANG ; Xiulan SHI ; Xin ZHOU
Journal of Southern Medical University 2024;44(6):1126-1134
Objective To investigate the protective effect of recombinant Schistosoma japonicum cystatin(rSj-Cys)against acute liver injury induced by lipopolysaccharide(LPS)and D-GalN in mice.Methods Adult male C57BL/6J mice with or without LPS/D-GaIN-induced acute liver injury were given intraperitoneal injections of rSj-Cys or PBS 30 min after modeling(n=18),and serum and liver tissues samples were collected from 8 mice in each group 6 h after modeling.The survival of the remaining 10 mice in each group within 24 h was observed.Serum levels of ALT,AST,TNF-α and IL-6 of the mice were measured,and liver pathologies was observed with HE staining.The hepatic expressions of macrophage marker CD68,Bax,Bcl-2 and endoplasmic reticulum stress(ERS)-related proteins were detected using immunohistochemistry or immunoblotting,and TUNEL staining was used to detect hepatocyte apoptosis.Results The survival rates of PBS-and rSj-Cys-treated mouse models of acute liver injury were 30%and 80%at 12 h and were 10%and 60%at 24 h after modeling,respectively;no death occurred in the two control groups within 24 h.The mouse models showed significantly increased serum levels of AST,ALT,IL-6 and TNF-α and serious liver pathologies with increased hepatic expressions of CD68 and Bax,lowered expression of Bcl-2,increased hepatocyte apoptosis,and up-regulated expressions of ERS-related signaling pathway proteins GRP78,CHOP and NF-κB p-p65.Treatment of the mouse models significantly lowered the levels of AST,ALT,IL-6 and TNF-α,alleviated liver pathologies,reduced hepatic expressions of CD68,Bax,GRP78,CHOP and NF-κB p-p65,and enhanced the expression of Bcl-2.In the normal control mice,rSj-Cys injection did not produce any significant changes in these parameters compared with PBS.Conclusion rSj-Cys alleviates LPS/D-GalN-induced acute liver injury in mice by suppressing ERS,attenuating inflammation and inhibiting hepatocyte apoptosis.
6.Analysis of sleep status and impact factor of patients in clinical trials of antineoplastic drugs
Lingjun LI ; Weiying ZHANG ; Wenjin WANG ; Xiuyue YANG ; Yuting HU ; Jing WANG ; Xinlu YAN
Chinese Journal of Practical Nursing 2024;40(29):2279-2284
Objective:To explore the sleep status and impact factor analysis of patients in clinical trials of antineoplastic drugs, and provide a basis for improving the sleep status and impact analysis of patients in clinical trials of antineoplastic drugs.Methods:From April to May 2023, 107 oncology patients in the Phase I Clinical Trial Ward of the Affiliated East Hospital of Tongji University were selected as the research objects by convenient sampling method. The general information questionnaire, Pittsburgh Sleep Quality Index Scale (PSQI), Numeric rating scale (NRS), Generalized Anxiety Disorder Scale (GAD-7) and Depression Self-Ration Tool Scale (PHQ-9). Multivariate Logistic regression analysis methods were used to carry out a cross-sectional investigation and the relevant factors affecting patients′sleep.Results:Totally 103 questionnaires were effectively collected. The 103 patients′ age ranged from 20 to 75 years old, including 61 males and 42 females. 47.57% (49/103) patients in clinical trials of antineoplastic drugs had abnormal sleep. The average score of patients (PSQI) (7.66 ± 3.93) was higher than the average score of the domestic norm (3.88 ± 2.52), and there was significant statistical difference ( t = 9.76, P<0.01). Logistic regression analysis showed that pain ( OR = 3.004, 95% CI 1.135-7.948, P<0.05) and trial cycle ( OR = 0.432, 95% CI 0.191-0.978, P<0.05) were significant risk factors for abnormal sleep quality. Conclusions:The incidence of abnormal sleep quality in patients of clinical trials of antineoplastic drugs is high, but the sleep quality is poor. The factors that affect the sleep quality of patients in clinical trials of antineoplastic drugs are mainly related to the patient′s trial cycle and cancer pain. According to these characteristics, individualized programs should be developed to improve the sleep quality of patients with advanced cancer, so as to improve the quality of life of patients with advanced cancer.
7.Recombinant Schistosoma japonicum cystatin alleviates acute liver injury in mice by inhibiting endoplasmic reticulum stress,inflammation and hepatocyte apoptosis
Lingjun LU ; Xiaodi YANG ; Huaping ZHANG ; Yuan LIANG ; Xiulan SHI ; Xin ZHOU
Journal of Southern Medical University 2024;44(6):1126-1134
Objective To investigate the protective effect of recombinant Schistosoma japonicum cystatin(rSj-Cys)against acute liver injury induced by lipopolysaccharide(LPS)and D-GalN in mice.Methods Adult male C57BL/6J mice with or without LPS/D-GaIN-induced acute liver injury were given intraperitoneal injections of rSj-Cys or PBS 30 min after modeling(n=18),and serum and liver tissues samples were collected from 8 mice in each group 6 h after modeling.The survival of the remaining 10 mice in each group within 24 h was observed.Serum levels of ALT,AST,TNF-α and IL-6 of the mice were measured,and liver pathologies was observed with HE staining.The hepatic expressions of macrophage marker CD68,Bax,Bcl-2 and endoplasmic reticulum stress(ERS)-related proteins were detected using immunohistochemistry or immunoblotting,and TUNEL staining was used to detect hepatocyte apoptosis.Results The survival rates of PBS-and rSj-Cys-treated mouse models of acute liver injury were 30%and 80%at 12 h and were 10%and 60%at 24 h after modeling,respectively;no death occurred in the two control groups within 24 h.The mouse models showed significantly increased serum levels of AST,ALT,IL-6 and TNF-α and serious liver pathologies with increased hepatic expressions of CD68 and Bax,lowered expression of Bcl-2,increased hepatocyte apoptosis,and up-regulated expressions of ERS-related signaling pathway proteins GRP78,CHOP and NF-κB p-p65.Treatment of the mouse models significantly lowered the levels of AST,ALT,IL-6 and TNF-α,alleviated liver pathologies,reduced hepatic expressions of CD68,Bax,GRP78,CHOP and NF-κB p-p65,and enhanced the expression of Bcl-2.In the normal control mice,rSj-Cys injection did not produce any significant changes in these parameters compared with PBS.Conclusion rSj-Cys alleviates LPS/D-GalN-induced acute liver injury in mice by suppressing ERS,attenuating inflammation and inhibiting hepatocyte apoptosis.
8.Epidemiological Analysis of Pathogens in Acute Respiratory Infections During the 2023—2024 Autumn-Winter Season in Beijing: A Case Series of 5556 Patients at Peking Union Medical College Hospital
Yan CAO ; Yu CHEN ; Jie YI ; Lingjun KONG ; Ziyi WANG ; Rui ZHANG ; Qi YU ; Yiwei LIU ; MULATIJIANG MAIMAITI ; Chenglin YANG ; Yujie SUN ; Yingchun XU ; Qiwen YANG ; Juan DU
Medical Journal of Peking Union Medical College Hospital 2024;16(3):680-686
To analyze the epidemiological characteristics of acute respiratory infections (ARIs) during the autumn-winter season in Beijing, providing evidence for the prevention, control, diagnosis, and treatment of ARIs. A convenience sampling method was employed, enrolling patients who visited Peking Union Medical College Hospital (PUMCH) between September 2023 and February 2024 due to ARIs. Nasopharyngeal swabs were collected, and real-time fluorescence quantitative PCR was used to detect six common respiratory pathogens[influenza A virus (FluA), influenza B virus (FluB), human rhinovirus (HRV), A total of 5556 eligible patients were included. The overall positivity rate for the six common respiratory pathogens was 63.7%, with single-pathogen positivity at 54.0%, dual-pathogen positivity at 8.9%, and triple or more pathogen positivity at 0.7%. The predominant pathogens detected were FluA(16.1%) and RSV(15.7%), followed by ADV(11.1%), MP(11.1%), HRV(10.0%), and FluB(10.0%).No significant difference in overall pathogen positivity was observed between genders.However, significant differences were found between autumn and winter( The prevalence of respiratory pathogens in Beijing is associated with age and season. Targeted preventive measures should be implemented in different seasons and for key populations.
9.Establishment and evaluation of a nomogram model for predicting the risk of sepsis in diabetic foot patients
Lingjun LIN ; Junwei WANG ; Yongli WAN ; Yang GAO
Chinese Critical Care Medicine 2024;36(7):693-698
Objective:To establish a nomogram model for predicting the risk of sepsis in diabetic foot patients, and to provide reference for clinical prevention and treatment.Methods:The clinical data of 430 patients with diabetic foot who were hospitalized in Chu Hsien-I Memorial Hospital of Tianjin Medical University from January 2022 to March 2023 were reviewed and collected, including age, gender, past medical history, smoking and drinking history, family history, diabetes course, Texas grade of diabetic foot and laboratory indicators within 24 hours after admission. Patients were divided into sepsis group and non-sepsis group according to the presence or absence of sepsis during hospitalization. The differences in clinical data between the two groups were compared. Multivariate Logistic regression analysis was used to screen the influencing factors of sepsis in patients with diabetic foot during hospitalization, and a nomogram predictive model was established. The performance of the prediction model was evaluated by receiver operator characteristic curve (ROC curve), calibration curve and decision curve analysis (DCA). Internal validation was performed by using Bootstrap method.Results:A total of 430 patients were enrolled, among which 90 patients developed sepsis during hospitalization and 340 patients did not. There were statistically significant differences in diabetes course, Texas grade of diabetic foot, white blood cell count (WBC), neutrophil count (NEU), lymphocyte count (LYM), neutrophil to lymphocyte ratio (NLR), hemoglobin (Hb), albumin (Alb), glycosylated hemoglobin (HbA1c), C-reactive protein (CRP), and blood urea nitrogen (BUN) between the two groups. Multivariate Logistic regression analysis showed that diabetes course [odds ratio ( OR) = 2.774, 95% confidence interval (95% CI) was 1.053-7.308, P = 0.039], Texas grade of diabetic foot ( OR = 2.312, 95% CI was 1.014-5.273, P = 0.046), WBC ( OR = 1.160, 95% CI was 1.042-1.291, P = 0.007), HbA1c ( OR = 1.510, 95% CI was 1.278-1.784, P < 0.001), CRP ( OR = 1.007, 95% CI was 1.000-1.014, P = 0.036) were independent risk factors for sepsis in patients with diabetic foot during hospitalization, while Alb was a protective factor ( OR = 0.885, 95% CI was 0.805-0.972, P = 0.011). A nomogram predictive model was constructed based on the above 6 indicators. The ROC curve showed that the area under ROC curve (AUC) of the nomogram predictive model for identifying the sepsis patients was 0.919 (95% CI was 0.889-0.948). The AUC of the nomogram predictive model after internal verification was 0.918 (95% CI was 0.887-0.946). Hosmer-Lemeshow test showed χ2 = 2.978, P = 0.936, indicating that the calibration degree of the predictive model was good. Calibration curve showed that the predicted probability of sepsis was in good agreement with the actual probability. DCA curve showed that the nomogram predictive model had good clinical usefulness. Conclusion:The nomogram predictive model based on the risk factors of diabetes course, Texas grade of diabetic foot, WBC, HbA1c, CRP and Alb has good predictive value for the occurrence of sepsis in patients with diabetic foot during hospitalization, which is helpful for clinical screening of the possibility of diabetic foot patients progressing to sepsis, and timely personalized intervention for different patients.
10.Laxation Atherosclerosis of Guizhi Tongluo Tablets by Inhibiting Neutrophil Extracellular Trapping Nets
Qiuyun LYU ; Lin YANG ; Dong SHEN ; Xiaojing HUANG ; Xianmei PAN ; Senjie ZHONG ; Jie CHEN ; Lingjun WANG ; Shaoxiang XIAN ; Wenhua XU ; Hongcheng FANG
Herald of Medicine 2024;43(12):1898-1903
Objective To investigate the mechanism of Guizhi Tongluo Tablets(GZTLP)on improving atherosclerosis in APOE knockout mice by regulating neutrophil extracellular trapping nets(NETs).Methods After modeling,24 APOE knockout mice aged 8 weeks were randomly divided into 4 groups:GZTLP high-dose group,low-dose group,model control group and normal control group,with 6 mice in each group.GZTLP was given 1.87 mg·g-1 and 0.47 mg·g-1 intragastric administration in high-dose group and low-dose group,respectively.The normal control group and model control group were given 0.9%sodium chloride solution intragastric administration for 6 weeks,and the lipid plaque deposition in aorta was observed by gross oil red O staining.Lipid deposition in aortic root was observed by oil red O staining.The pathological changes of lipid plaques in aortic root were observed by HE staining.The levels of interleukin-1β(IL-1β)and tumor necrosis factor α(TNF-α)in peripheral blood of mice were detected by enzyme-linked immunosorbent assay(ELISA).The expression of lymphocyte antigen 6G(Ly6G),myeloperoxidase(MPO)and citrulinated histone(Cit-H3)in plaques of the aortic arch and the colocalization of Ly6G,MPO and Cit-H3 were detected by immunofluorescence assay.Results Compared with the normal control group,the aorta of mice in the model control group showed serious lipid plaque deposition,morphological damage,and a large number of inflammatory cells infiltration,the contents of serum inflammatory factors IL-1β and TNF-α were increased,and the protein expressions of Ly6G,Cit-H3 and MPO were significantly increased.Compared with model control group,GZTLP group reduced the amount of lipid plaque deposition in aorta,the arrangement of aortic cells was more regular,the inflammatory cell infiltration was improved,and the contents of serum inflammatory factors IL-1β and TNF-α were significantly decreased(P<0.05).The colocalization and the protein expression of Ly6G,MPO and Cit-H3 were significantly decreased in aortic tissues(P<0.01).Conclusions GZTLP can improve atherosclerosis,and its mechanism may be related to the inhibition of neutrophil extracellular trapping nets.


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