1.Arterial aging in naturally aging Wistar rats and the intervention effect of Rhizoma Polygonati
Zhen QIN ; Yongfang SHI ; Qin ZHAO ; Na LI ; Jianwei XU ; Libing YE
Acta Laboratorium Animalis Scientia Sinica 2025;33(10):1422-1430
Objective To explore the effect of Rhizoma Polygonati(RP)on arterial aging in naturally aging Wistar rats.Methods SPF Wistar rats aged 72 weeks were divided randomly divided into 4 groups:an old group and RP low,medium,and high-dose groups(n=14 rats per group).Another 14 male SPF Wistar rats aged 8~12 weeks were selected as the young group.Rats in the RP high,medium,and low-dose groups were administered with 4,2,and 1 g/kg RP,respectively,by gavage,and rats in the old and young groups were given the same amount of distilled water once a day for 12 weeks.Seven rats from each group were sacrificed under anesthesia at weeks 4 and 12 and aortas were isolated.The relative smooth muscle cell(SMC)and collagen fiber(CF)contents were analyzed,total antioxidant capacity(T-AOC),glutathione peroxidase(GSH-Px),superoxide dismutase(SOD),and malondialdehyde(MDA)levels were measured,and the expression levels of cell cycle-associated proteins in arterial tissue were detected by Western Blot.Results Rats in the old group showed obvious signs of vascular aging but there was no significant changes in arterial vascular tissue indexes in the old group with increased age.Aortas were obviously injured,relative contents of SMC and CF were significantly increased(P<0.01),T-AOC,SOD,and GSH-Px contents were significantly decreased and MDA was increased(P<0.01)in the old group compared with the young group at 4 and 8 weeks,and expression levels of cell cycle-associated proteins were significantly up-regulated(P<0.01).RP intervention significantly decreased the relative SMC and CF contents and MDA levels(P<0.05 or P<0.01)and significantly increased T-AOC,SOD,and GSH-Px(P<0.05 or P<0.01).Expression levels of cell cycle-associated proteins were also significantly decreased(P<0.05 or P<0.01).High-dose RP had the greatest effect.Conclusions Arterial aging is relatively stable in the short term in naturally aging rats.RP could delay arterial aging in naturally aging rats by regulating the level of oxidative stress and the expression of cell cycle-associated proteins.
2.Arterial aging in naturally aging Wistar rats and the intervention effect of Rhizoma Polygonati
Zhen QIN ; Yongfang SHI ; Qin ZHAO ; Na LI ; Jianwei XU ; Libing YE
Acta Laboratorium Animalis Scientia Sinica 2025;33(10):1422-1430
Objective To explore the effect of Rhizoma Polygonati(RP)on arterial aging in naturally aging Wistar rats.Methods SPF Wistar rats aged 72 weeks were divided randomly divided into 4 groups:an old group and RP low,medium,and high-dose groups(n=14 rats per group).Another 14 male SPF Wistar rats aged 8~12 weeks were selected as the young group.Rats in the RP high,medium,and low-dose groups were administered with 4,2,and 1 g/kg RP,respectively,by gavage,and rats in the old and young groups were given the same amount of distilled water once a day for 12 weeks.Seven rats from each group were sacrificed under anesthesia at weeks 4 and 12 and aortas were isolated.The relative smooth muscle cell(SMC)and collagen fiber(CF)contents were analyzed,total antioxidant capacity(T-AOC),glutathione peroxidase(GSH-Px),superoxide dismutase(SOD),and malondialdehyde(MDA)levels were measured,and the expression levels of cell cycle-associated proteins in arterial tissue were detected by Western Blot.Results Rats in the old group showed obvious signs of vascular aging but there was no significant changes in arterial vascular tissue indexes in the old group with increased age.Aortas were obviously injured,relative contents of SMC and CF were significantly increased(P<0.01),T-AOC,SOD,and GSH-Px contents were significantly decreased and MDA was increased(P<0.01)in the old group compared with the young group at 4 and 8 weeks,and expression levels of cell cycle-associated proteins were significantly up-regulated(P<0.01).RP intervention significantly decreased the relative SMC and CF contents and MDA levels(P<0.05 or P<0.01)and significantly increased T-AOC,SOD,and GSH-Px(P<0.05 or P<0.01).Expression levels of cell cycle-associated proteins were also significantly decreased(P<0.05 or P<0.01).High-dose RP had the greatest effect.Conclusions Arterial aging is relatively stable in the short term in naturally aging rats.RP could delay arterial aging in naturally aging rats by regulating the level of oxidative stress and the expression of cell cycle-associated proteins.
3.Research progress on the pathogenesis of hydroxychloroquine retinopathy and the related fundus changes
Yongfang ZHONG ; Xuemei XU ; Haibin WANG
Chinese Journal of Ocular Fundus Diseases 2024;40(9):729-732
Hydroxychloroquine retinopathy is an ocular lesions that develops following long-term or excessive use of hydroxychloroquine. The early clinical presentation of this lesion is nonspecific and is often detected when severe central vision impairment occurs in late stage. It currently mainly includes hydroxychloroquine binding to melanin, inducing degeneration of the retinal pigment epithelium, increasing the pH of lysosomes in the retinal pigment epithelium and interfering with the visual cycle. In recent years, with the development of retinal imaging technology and the in-depth study of hydroxychloroquine retinopathy, characteristic fundus structural changes such as retinal and choroidal thickness and blood vessels may occur in the early stage. This not only provides an important basis for the early diagnosis of hydroxychloroquine retinopathy, but also provides important clues for investigating its pathogenesis. Clinicians' proficiency in relevant fundus changes and pathogenesis will facilitate early diagnosis and treatment, while also minimizing irreversible central vision impairment in patients.
4.Study on the influencing factors and predictive biomarkers of immune-related adverse events caused by tislelizumab in patients with malignant tumors
Hui ZHU ; Yongfang YUAN ; Ying XU
Adverse Drug Reactions Journal 2024;26(1):18-24
Objective:To explore the occurrence, influencing factors, and predictive biomarkers of immune-related adverse events (irAEs) in malignant tumor patients treated with tislelizumab.Methods:The electronic medical records of adult patients with malignant tumors, who received tislelizumab for at least one cycle from June 2020 to June 2023 at Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine, were collected, and the occurrence and clinical characteristics of irAEs were retrospectively analyzed. Patients were divided into irAEs group and non-irAEs group according to whether they had irAEs. The clinical characteristics and detection value of biomarkers in patients of the 2 groups were compared. Multivariate logistic regression was used to analyze the risk factors of irAEs in patients. The receiver operating characteristic (ROC) curve was used to find the cutoff point of the biomarkers for predicting the irAEs.Results:A total of 107 patients were entered, including 81 males (75.7%) and 26 females (24.3%), aged (61±15) years. Among them, 25 patients (23.4%) were diagnosed with tislelizumab-related irAEs, of which 6 patients (5.6%) had irAEs with a severity of grade 3 and above. A total of 28 irAEs occurred in the 25 patients, including 9 cases of thyroid dysfunction, 4 cases of immune-related enteritis, 4 cases of rashes, 3 cases of immune-related pneumonitis, 3 cases of kidney injury, 3 cases of liver injury, 1 case of immune-related myositis, and 1 case of hypertension. The median treatment cycle from the start of tislelizumab to the occurrence of irAEs was 3 (1, 5) cycles. After discontinuation of tislelizumab and/or glucocorticoids and symptomatic treatments, all 25 patients were improved. No deaths occurred due to irAEs. The results of multivariate logistic regression analysis showed that a high neutrophil-to-lymphocyte ratio (NLP) at baseline was a protective factor for irAEs [odds ratio ( OR)=0.453, 95% confidence interval ( CI): 0.279-0.735, P=0.001], while a high platelet-to-lymphocyte ratio (PLR) at baseline was a risk factor ( OR=1.006, 95% CI: 1.002-1.011, P=0.008). The ROC curve analysis results showed that the cutoff points of NLR and PLR at baseline for predicting the occurrence of irAEs were 1.58 (sensitivity: 0.988; specificity: 0.644) and 159.40 (sensitivity: 0.800; specificity: 0.524), respectively. Conclusions:The incidence of irAEs in the tislelizumab treatment for adult malignant tumors was 23.4%. Thyroid dysfunction is most common and attentions should also be paid to immune-related enteritis, rashes, immune-related pneumonitis, kidney injury, and liver injury. Baseline levels of NLR and PLR may be biomarkers for predicting irAEs.
5.Current situation of water resource utilization and its improvement suggestion in a certain naval station
Xiao PENG ; Xiaochuan HOU ; Yina ZHU ; Zhaoyun PENG ; Yuan YAO ; Yongfang WANG ; Zheng XU ; Liang XIAO
Journal of Navy Medicine 2024;45(5):464-468
In light of the scarcity of freshwater resources and challenges in ensuring potable water supply at naval stations,the entire process of drinking water supply at a naval station was comprehensively investigated by field surveys and inquiries.The drinking water supply of the naval station was significantly affected by low and high water periods,and the water quality was poor.The water purification was insufficient.The freshwater collected through groundwater or rainwater had a poor taste,which resulted in a low level of satisfaction among officers and soldiers.In consideration of the meteorological characteristics and water resources utilization status at the island observation station,this study presents recommendations for enhancing the drinking water supply for officers and soldiers stationed there.Furthermore,this study discusses the feasibility of implementing air-to-water production technology to improve the quality of drinking water at the naval island stations,thereby safeguarding personnel health and maintaining combat effectiveness.
6.Study on the influencing factors and predictive biomarkers of immune-related adverse events caused by tislelizumab in patients with malignant tumors
Hui ZHU ; Yongfang YUAN ; Ying XU
Adverse Drug Reactions Journal 2024;26(1):18-24
Objective:To explore the occurrence, influencing factors, and predictive biomarkers of immune-related adverse events (irAEs) in malignant tumor patients treated with tislelizumab.Methods:The electronic medical records of adult patients with malignant tumors, who received tislelizumab for at least one cycle from June 2020 to June 2023 at Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine, were collected, and the occurrence and clinical characteristics of irAEs were retrospectively analyzed. Patients were divided into irAEs group and non-irAEs group according to whether they had irAEs. The clinical characteristics and detection value of biomarkers in patients of the 2 groups were compared. Multivariate logistic regression was used to analyze the risk factors of irAEs in patients. The receiver operating characteristic (ROC) curve was used to find the cutoff point of the biomarkers for predicting the irAEs.Results:A total of 107 patients were entered, including 81 males (75.7%) and 26 females (24.3%), aged (61±15) years. Among them, 25 patients (23.4%) were diagnosed with tislelizumab-related irAEs, of which 6 patients (5.6%) had irAEs with a severity of grade 3 and above. A total of 28 irAEs occurred in the 25 patients, including 9 cases of thyroid dysfunction, 4 cases of immune-related enteritis, 4 cases of rashes, 3 cases of immune-related pneumonitis, 3 cases of kidney injury, 3 cases of liver injury, 1 case of immune-related myositis, and 1 case of hypertension. The median treatment cycle from the start of tislelizumab to the occurrence of irAEs was 3 (1, 5) cycles. After discontinuation of tislelizumab and/or glucocorticoids and symptomatic treatments, all 25 patients were improved. No deaths occurred due to irAEs. The results of multivariate logistic regression analysis showed that a high neutrophil-to-lymphocyte ratio (NLP) at baseline was a protective factor for irAEs [odds ratio ( OR)=0.453, 95% confidence interval ( CI): 0.279-0.735, P=0.001], while a high platelet-to-lymphocyte ratio (PLR) at baseline was a risk factor ( OR=1.006, 95% CI: 1.002-1.011, P=0.008). The ROC curve analysis results showed that the cutoff points of NLR and PLR at baseline for predicting the occurrence of irAEs were 1.58 (sensitivity: 0.988; specificity: 0.644) and 159.40 (sensitivity: 0.800; specificity: 0.524), respectively. Conclusions:The incidence of irAEs in the tislelizumab treatment for adult malignant tumors was 23.4%. Thyroid dysfunction is most common and attentions should also be paid to immune-related enteritis, rashes, immune-related pneumonitis, kidney injury, and liver injury. Baseline levels of NLR and PLR may be biomarkers for predicting irAEs.
7.Comparison of clinical effects of a novel stent assisted intestinal bypass and temporary loop ileostomy in laparoscopic low anterior resection of rectal cancer
Liushiyang XU ; Shiyu HU ; Wanbo HUANG ; Jianming XIE ; Jiabin YANG ; Yongfang YIN ; Haixiang DING ; Zhilong YAN
Chinese Journal of General Surgery 2023;38(6):401-406
Objective:To compare the clinical value of stent assisted intestinal bypass and temporary loop ileostomy in laparoscopic low anterior resection of rectal cancer.Method:In this retrospective analysis, 57 patients undergoing laparoscopic low anterior resection for rectal cancer in the First Affiliated Hospital of Ningbo University from Jan 2020 to Jan 2022 were divided into intestinal bypass group (36 cases) and loop ileostomy group (21 cases).Result:There were no significant differences in postoperative GI function recovery and postoperative complication rate between the two groups (all P>0.05). The levels of albumin, prealbumin and hemoglobin in the intestinal bypass group were better than those in the ileostomy group when evaluated on 3rd months after operation [(40.5±2.3) g/L vs. (38.1±2.6)g/L、(26.4±2.7)mg/dl vs. (24.5±2.0)mg/dl、(137.6±5.9) g/L vs. (134.0±7.0) g/L, t=3.605、2.743、2.085, all P<0.05]. Hospital expenses of the intestinal bypass group was lower [(571 000±7 500) yuan vs. (69 300±9 100) yuan, t=-5.477, P<0.05]. Conclusion:Compared with traditional ileostomy, the stent assisted intestinal bypass reduces trauma with lower expenses and improves patients' status after laparoscopic low anterior resection for rectal cancer.
8.Combating COVID-19 with integrated traditional Chinese and Western medicine in China.
Liqiang NI ; Lili CHEN ; Xia HUANG ; Chouping HAN ; Jianrong XU ; Hong ZHANG ; Xin LUAN ; Yongfang ZHAO ; Jianguang XU ; Weian YUAN ; Hongzhuan CHEN
Acta Pharmaceutica Sinica B 2020;10(7):1149-1162
COVID-19, an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread throughout the world. China has achieved rapid containment of this highly infectious disease following the principles of early detection, early quarantine and early treatment with integrated traditional Chinese and Western medicine. The inclusion of traditional Chinese medicine (TCM) in the Chinese protocol is based on its successful historic experience in fighting against pestilence. Current findings have shown that the Chinese medicine can reduce the incidence of severe or critical events, improve clinical recovery and help alleviate symptoms such as cough or fever. To date there are over 133 ongoing registered clinical studies on TCM/integrated traditional Chinese and Western medicine. The three Chinese patent medicines (/ (Forsythiae and Honeysuckle Flower Pestilence-Clearing Granules/Capsules), (Honeysuckle Flower Cold-Relieving Granules) and (Stasis-Resolving & Toxin-Removing) were officially approved by the National Medical Products Administration to list COVID-19 as an additional indication. The pharmacological studies have suggested that Chinese medicine is effective for COVID-19 probably through its host-directed regulation and certain antiviral effects.
9.Effects of drinking water-borne arsenic exposure on mammary gland development of female mice in early life
Yongfang LI ; Dianqi YAO ; Hao LUO ; Xing ZHANG ; Dongmeng MEI ; Guifan SUN ; Yuanyuan XU
Chinese Journal of Endemiology 2020;39(12):876-880
Objective:To investigate the effects of drinking water-borne arsenic exposure on mammary gland development of female mice in early life.Methods:Healthy and sexually mature C57BL/6J mice were paired according to the female to male ratio of 2∶1. After confirmation of pregnancy, female mice were randomly divided into control (drinking double distilled water), low- (0.5 mg/L) and high- (5.0 mg/L) dose arsenic exposure groups, 10 mice in each group. The exposure time of arsenic in drinking water ranged from day 0 of pregnancy to day 28 after birth. At the end of arsenic exposure, female offspring (10 mice in each group) were sacrificed and mammary glands were dissected for whole tissue staining to evaluate the development of mammary glands and quantitative analysis of mammary gland development indexes. The expression of proliferating cell associated antigen Ki67 was detected by immunohistochemistry.Results:There were no significant differences in body weight and organ coefficients of liver, kidney and mammary glands between female offspring in low- and high-dose arsenic exposure groups and control group ( F=1.018, 1.033, 1.764, 0.199, P > 0.05). Compared with control group, low- and high- dose arsenic exposure groups showed more terminal end buds (TEB) and ductal branches as well as stronger longitudinal growth ability in mammary gland morphological analysis. Quantitative analysis results showed that the numbers of TEB in the low- and high-dose arsenic exposure groups (11.83 ± 4.40, 11.00 ± 3.74) were significantly higher than that in the control group (4.00 ± 1.83, P < 0.05). The ductal lengths in the low- and high-dose arsenic exposure groups [(6.43 ± 1.08), (6.08 ± 1.74) mm] were also significantly longer than that in the control group [(3.71 ± 0.61) mm, P < 0.05]. The distance of leading edge of ducts to the midpoint of lymph nodes in the low- and high-dose arsenic exposure groups [(0.58 ± 1.12), (- 0.02 ± 1.57) mm] was significantly shorter than that in the control group [(- 2.67 ± 0.87) mm, P < 0.05]. The mean maximum area of TEB in the low-dose arsenic exposure group [(0.04 ± 0.01) mm 2] was significantly larger than that in the control group [(0.02 ± 0.01) mm 2, P < 0.05]. Immunohistochemistry staining indicated strong staining of Ki67 within TEB in the low- and high-dose arsenic exposure groups. Conclusion:Early life inorganic arsenic exposure promotes the development of TEB, ductal extension and cell proliferation within TEB in female mice, indicating that early life arsenic exposure alters mammary gland development.
10.Etiological characteristics and change of cerebrospinal fluid related measurements in AIDS patients with central nervous system infections in Chongqing
Xiaofeng LI ; Jing WANG ; Jing HE ; Kun YANG ; Xu ZHANG ; Yongfang HU ; Dongyong WAN
Chinese Journal of Experimental and Clinical Virology 2020;34(5):516-521
Objective:To analyze the distribution and drug sensitivity of pathogens and cerebrospinal fluid (CSF) related measurements in AIDS patients with central nervous system (CNS) infections in Chongqing, so as to provide guidance for etiological diagnosis and rational use of antibiotics in AIDS patients with CNS infections.Methods:A total of 173 AIDS patients with CNS infections were divided into fungal group, Gram-positive bacilli group, Gram-positive cocci group and Gram-negative bacilli group. During the same period, 198 AIDS patients with non-CNS infection visited this hospital were enrolled into the control group. CSF and blood were collected for bacterial culture. The composition and drug resistance of pathogens were analyzed. The levels of CSF related measurements were determined and compared.Results:A total of 173 strains of pathogens were isolated from the CSF of the AIDS patients with CNS infections. The 173 strains included 101 (58.38%) fungi, 39 (22.54%) Gram-positive bacilli, 24 (13.87%) Gram positive cocci and 9 (5.20%) Gram-negative bacilli; 230 strains of pathogens were isolated from the blood of the AIDS patients with non CNS infections. The 198 strains were composed of 107(54.04%) fungi, 65 (32.83%) Gram positive cocci and 26 (13.13%) Gram-negative bacilli. Antifungal sensitivity testing result of Cryptococcus neoformans showed that MIC of amphotericin B, fluorocytosine, fluconazole, voriconazole and itraconazole were≤4, ≤32, ≤8, ≤1 and ≤1 μg/ml. The resistance rate of Mycobacterium tuberculosis to rifampicin was 7.69%. The result of drug sensitivity of coagulase negative staphylococci isolated from patients with CNS infections and non-CNS infections were consistent. There were significant differences among Staphylococcus aureus, Enterobacteriaceae and Acinetobacter. Compared with the control group, the levels of protein were higher and the levels of chloride and glucose were lower in fungal group, Gram-positive bacteria group, Gram-positive coccus group and Gram-negative bacteria group ( t=3.408-9.249, all P<0.011). The levels of protein, adenosine deaminase (ADA) and lactic dehydrogenase (LDH) in Gram-positive bacilli group were significantly higher than those in fungal group, Gram-positive coccus group, Gram-negative bacteria group and control group ( t=3.836-7.686, all P<0.037). Conclusions:The pathogens causing CNS and blood infections in AIDS patients were widely distributed, mainly dominated by fungus. The CSF related measurements varied with different pathogens, so as to assist in the etiological diagnosis of CNS infections.

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