1.Exploring the Mechanism of Anti-asthma Effect of Fujiu Patch on Modulation of Th17/Treg Immune Balance Based on IL-6/STAT3 and IL-2/STAT5 Signaling Pathways
Kun FU ; Yan YANG ; Yiling LU ; Peng ZHONG ; Lan ZHAO ; Min XU
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(1):26-34
Objective This study aims to investigate the regulatory effects of Fujiu Patch(composed of Sinapis Semen,Kansui Radix,Corydalis Rhizoma and Asari Radix et Rhizoma)on the CD4+ T helper 17 cell(Th17)/CD4+CD25+ regulatory T cell(Treg)balance in asthmatic rats via the signal pathway of IL-6/signal transducer and activator of transcription 3(STAT3)as well as IL-2/signal transducer and activator of transcription 5(STAT5),and to reveal its anti-asthma mechanisms.Methods An experimental asthma model was constructed by ovalbumin(OVA)combined with aluminum hydroxide sensitization and challenge,and then the rats were administered with Fujiu Patch at Dazhui(DU14),Feishu(BL13)and Shenshu(BL23)points for 4 hours each time,once every other day for 7 times.Immunohistochemistry was used to detect the positive expressions of Th17 specific cytokine(IL-17)and Treg transcription factor(Foxp3)in rat lung tissue.The percentage of Th17 and Treg cells in peripheral blood was examined by flow cytometry analysis,and the expressions of IL-6/STAT3 and IL-2/STAT5 pathway-related proteins in lung tissue were assayed with Western Blot.Results Compared to the model group,IL-17 positive expression in the rat lung showed a significant reduction in the Fujiu Patch group(P<0.01),while the positive expression of Foxp3 was obviously increased(P<0.05).Meanwhile,the protein expression levels of IL-6 and phospho-STAT3 were were significantly declined(P<0.01),and the protein expression levels of IL-2 and phospho-STAT5 were were significantly elevated(P<0.01).However,there was no significant alteration in the total protein expressions of STAT3 and STAT5(P>0.05).Furthermore,the proportion of Th17 cells in peripheral blood of rats in the Fujiu Patch group was lower than that in the model group,while the proportion of Treg cells was higher than that in the model group.Statistically-significant differences were observed(all P<0.01).Conclusion These findings indicate that Th17/Treg immune imbalance occurs in asthmatic rat.Fujiu Patch may exert anti-asthma effects via inhibiting the expression of IL-6,downregulating the expression of phospho-STAT3,diminishing the level of IL-17-producing Th17 cells,as well as increasing the expressions of IL-2-mediated STAT5 phosphorylation,raising the level of Foxp3-expressing Treg cells,promoting Th17/Treg balance and suppressing immune responses in rat with asthma.
2.Factors influencing advance care planning engagement behavior in patients with advanced cancer:a systematic review
Yiling FU ; Qian WU ; Xiaoqing LUO ; Aihong WU ; Xuelan XIA ; Min ZHENG
Journal of Shanghai Jiaotong University(Medical Science) 2024;44(4):482-493
Objective·To systematically integrate relevant influencing factors of advanced cancer patients'engagement behavior in advance care planning(ACP).Methods·The systematic search of Chinese and English literature on factors influencing ACP engagement behavior in advanced cancer patients from inception to December 2022 in China National Knowledge Infrastructure(CNKI),Wanfang,China Biomedical Literature Database(Sinomed),PubMed,Cochrane Library,Embase,CINAHL,and PsycINFO was conducted.After the literature quality evaluation,content extraction and summary were conducted by two researchers,and the data of quantitative research and qualitative research were extracted and integrated respectively.The final influencing factors of ACP engagement behavior of advanced cancer patients were obtained.With the help of the theoretical domain,they were mapped to the capability,opportunity,motivation-behavior(COM-B)model step by step.Results·A total of 21 studies were included and 27 factors were summarized,including 9 theoretical domains.Mapping to the COM-B model included 9 capability factors(knowledge of ACP,education level,accurate knowledge of prognosis,knowledge of the time of disease diagnosis,prior experience,subjective life expectancy,age,cancer site,and disease symptom burden),13 opportunity factors(gender,marital status,race/ethnicity,religious belief,dependent children,family economic condition,place of living,housing type,family support,social support,doctor-patient relationship,acculturation,and whether or not to establish a hospice service center)and 5 motivational factors(ACP attitude,ACP belief,ACP motivation,anxiety and depression,and death attitude).Among them,doctor-patient relationship,religious belief,ACP attitude,educational level,marital status,family support,knowledge of ACP,accurate knowledge of prognosis,age,place of living,attitude toward death,prior experience,and race/ethnicity were more influential factors on ACP engagement behavior.Conclusion·Based on the COM-B model,the influencing factors of ACP engagement behavior in advanced cancer patients can be comprehensively summarized.Future studies can use the above factors as an entry point to design continuous,multifaceted,and comprehensive interventions based on the COM-B model to promote the practice of ACP engagement behavior in advanced cancer patients.
3.Impact of different diagnostic criteria for assessing mild micro-hepatic encephalopathy in liver cirrhosis: an analysis based on a prospective, multicenter, real-world study
Xiaoyan LI ; Shanghao LIU ; Chuan LIU ; Hongmei ZU ; Xiaoqing GUO ; Huiling XIANG ; Yan HUANG ; Zhaolan YAN ; Yajing LI ; Jia SUN ; Ruixin SONG ; Junqing YAN ; Qing YE ; Fei LIU ; Lei HUANG ; Fanping MENG ; Xiaoning ZHANG ; Shaoqi YANG ; Shengjuan HU ; Jigang RUAN ; Yiling LI ; Ningning WANG ; Huipeng CUI ; Yanmeng WANG ; Chuang LEI ; Qinghai WANG ; Hongling TIAN ; Zhangshu QU ; Min YUAN ; Ruichun SHI ; Xiaoting YANG ; Dan JIN ; Dan SU ; Yijun LIU ; Ying CHEN ; Yuxiang XIA ; Yongzhong LI ; Qiaohua YANG ; Huai LI ; Xuelan ZHAO ; Zemin TIAN ; Hongji YU ; Xiaojuan ZHANG ; Chenxi WU ; Zhijian WU ; Shengqiang LI ; Qian SHEN ; Xuemei LIU ; Jianping HU ; Manqun WU ; Tong DANG ; Jing WANG ; Xianmei MENG ; Haiying WANG ; Zhenyu JIANG ; Yayuan LIU ; Ying LIU ; Suxuan QU ; Hong TAO ; Dongmei YAN ; Jun LIU ; Wei FU ; Jie YU ; Fusheng WANG ; Xiaolong QI ; Junliang FU
Chinese Journal of Hepatology 2023;31(9):961-968
Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.
4.Diagnostic value of a combined serology-based model for minimal hepatic encephalopathy in patients with compensated cirrhosis
Shanghao LIU ; Hongmei ZU ; Yan HUANG ; Xiaoqing GUO ; Huiling XIANG ; Tong DANG ; Xiaoyan LI ; Zhaolan YAN ; Yajing LI ; Fei LIU ; Jia SUN ; Ruixin SONG ; Junqing YAN ; Qing YE ; Jing WANG ; Xianmei MENG ; Haiying WANG ; Zhenyu JIANG ; Lei HUANG ; Fanping MENG ; Guo ZHANG ; Wenjuan WANG ; Shaoqi YANG ; Shengjuan HU ; Jigang RUAN ; Chuang LEI ; Qinghai WANG ; Hongling TIAN ; Qi ZHENG ; Yiling LI ; Ningning WANG ; Huipeng CUI ; Yanmeng WANG ; Zhangshu QU ; Min YUAN ; Yijun LIU ; Ying CHEN ; Yuxiang XIA ; Yayuan LIU ; Ying LIU ; Suxuan QU ; Hong TAO ; Ruichun SHI ; Xiaoting YANG ; Dan JIN ; Dan SU ; Yongfeng YANG ; Wei YE ; Na LIU ; Rongyu TANG ; Quan ZHANG ; Qin LIU ; Gaoliang ZOU ; Ziyue LI ; Caiyan ZHAO ; Qian ZHAO ; Qingge ZHANG ; Huafang GAO ; Tao MENG ; Jie LI ; Weihua WU ; Jian WANG ; Chuanlong YANG ; Hui LYU ; Chuan LIU ; Fusheng WANG ; Junliang FU ; Xiaolong QI
Chinese Journal of Laboratory Medicine 2023;46(1):52-61
Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.
5.Non-alcoholic fatty liver disease and ischemic stroke
Yiling FU ; Guilan LI ; Jia WANG ; Yinan LI ; Shuancheng GONG ; Xudong LU
International Journal of Cerebrovascular Diseases 2023;31(8):606-611
Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by excessive fat accumulation in the liver. More and more evidence suggests that NAFLD is a multisystem disease that affects multiple extra-hepatic organs. Recent studies have shown that NAFLD may be associated with the risk, severity, and outcome of ischemic stroke. The article provides a summary of these aspects.
6.Prevalence of HIV seropositivity and associated factors among the spouses of HIV/AIDS patients in Shanghai, 2018‒2022
Yiling ZHENG ; Minhong LIANG ; Chunyan HE ; Shuang XIAO ; Jie FU ; Leiming ZHOU ; Zeyu ZHANG ; Qing YUE ; Zhen NING
Shanghai Journal of Preventive Medicine 2023;35(11):1053-1057
ObjectiveTo analyze the HIV infection characteristics and influencing factors among the spouses of HIV/AIDS patients in Shanghai. MethodsA cross-sectional survey was conducted to collect demographic, behavioral, epidemiological and spousal HIV detection information of newly reported and married patients with HIV/AIDS in Shanghai from January 2018 to July 2022 in the comprehensive HIV prevention and control information system of Chinese Center for Disease Prevention and Control. Descriptive analysis was used to analyze the HIV positivity rate of the spouses of HIV patients and the influencing factors were analyzed by univariate and multivariate logistic regression models. ResultsA total of 1 233 subjects were investigated, and the first HIV-testing positivity rate of the spouses of HIV/AIDS patients was 29.3% (361/1 233). There were statistically significant differences in the HIV-testing positivity rate among spouses of HIV/AIDS patients by different age, gender, education level, occupation, transmission route, quantity of non-marital sexual activities, quantity of homo-sexual activities, and baseline CD4 cell count level (P<0.05). Spouses of the HIV/AIDS patients aged ≥65 years old, female, heterosexual transmission, less non-marital sex, and no history of homosexual sex had relatively high HIV positive rate. The HIV-positive detection rate of spouses in the ≥65 age group was 1.81 times higher than that in the <45 age group. The HIV-positive detection rate of spouses in the female group was 3.66 times higher than that in the male group, and the HIV-positive detection rate of spouses in the homosexual transmission group was 0.25 times higher than that of the heterosexual transmission group. ConclusionRisk awareness of HIV infection among married people with spouses should be improved. The key populations with the characteristics such as females as the first HIV-positive reporter, and heterosexual transmission should be paid special attention.Their spouses should be mobilized to conduct HIV-testing as early as possible
7.The analgesic mechanism of exosomes derived from umbilical cord mesenchymal stem cells in rats modelling osteoarthritis
Wenwen ZHOU ; Lin WANG ; Xinhe LI ; Yiling FU ; Juan LI ; Tieshan LI
Chinese Journal of Physical Medicine and Rehabilitation 2022;44(3):193-198
Objective:To observe any effect of exosomes derived from umbilical cord mesenchymal stem cells on pain, cartilage repair and the expression of transcriptional activator 3 (ATF-3) and growth related protein 43 (GAP-43) in the dorsal root ganglia (DRG), as well as to explore the mechanism of their relieving pain.Methods:Fifty-four male Sprague-Dawley rats were randomly divided into a sham-operation group, a monoiodoacetate group and an exosome group, each of 18. The knee cavities of the left hind limbs of all of the rats except those in the sham-operation group were injected with 50μl of monoiodoacetate to establish an arthritis pain model. The sham-operation group received only 50μl of saline solution as controls. Two weeks after the modelling, the knee joint cavities of the exosome group were injected with 50μl of exosomes, while the other two groups were injected with 50μl of normal saline. The rats′ mechanical and thermal pain thresholds were measured 1 day before the modeling, 7 and 14 days after the monoiodoacetate injection, as well as 7, 14 and 28 days after the exosome injection. Western blotting was used to detect the expression of ATF-3 and GAP-43 in the rats′ DRG, while hematoxylin and eosin staining was used to detect any cartilage repair.Results:Compared with the monoiodoacetate group, the latency of the mechanical and thermal pain thresholds had increased significantly in the exosome group 7 days after the exosome injection. The difference remained significant until the 28th day after the injection. The expression of ATF-3 protein decreased significantly and that of the GAP-43 protein increased significantly. Significant differences were observed in the average Osteoarthritis Research Society International (OARSI) knee cartilage score.Conclusions:Exosomes can alleviate the pain induced by monoiodoacetate adjuvant. The analgesic mechanism may be related to reducing nerve injury and promoting nerve and cartilage repair, with the nerve repair earlier than cartilage repair.
8.A prospective multicenter and real-world study on the diagnostic value of combination of number connection test-B and line tracing test in mild hepatic encephalopathy
Junqing YAN ; Hongmei ZU ; Jing WANG ; Xiaoqing GUO ; Xiaoyan LI ; Shanghao LIU ; Huiling XIANG ; Zhaolan YAN ; Tong DANG ; Haiying WANG ; Jia SUN ; Lei HUANG ; Fanping MENG ; Qingge ZHANG ; Guo ZHANG ; Yan HUANG ; Shaoqi YANG ; Shengjuan HU ; Jigang RUAN ; Yiling LI ; Chuang LEI ; Ying SONG ; Zhangshu QU ; Ruichun SHI ; Qin LIU ; Yijun LIU ; Qiaohua YANG ; Xuelan ZHAO ; Caiyan ZHAO ; Chenxi WU ; Qian SHEN ; Manqun WU ; Yayuan LIU ; Dongmei YAN ; Chuan LIU ; Junliang FU ; Xiaolong QI
Chinese Journal of Digestion 2022;42(10):659-666
Objective:To investigate the diagnostic value of independent and combined subtests of the psychometric hepatic encephalopathy score (PHES) in mild hepatic encephalopathy(MHE) of patients with liver cirrhosis, so as to optimize the PHES.Methods:This was a prospective, multicenter and real-world study which was sponsored by the National Clinical Research Center of Infectious Diseases and the Portal Hypertension Consortium. Twenty-six hospitals from 13 provinces, autonomous regions and municipalities countrywide participated in this study, induding Tianjin Third Central Hospital, the Fourth People′s Hospital of Qinghai Province, the Second Affiliated Hospital of Baotou Medical College, the Third People′s Hospital of Taiyuan, the Fifth Medical Center of PLA General Hospital and so on. From October 2021 to February 2022, outpatients and hospitalized patients with liver cirrhosis and no obvious hepatic encephalopathy were consecutively enrolled. All patients received 5 PHES subjects in the same order: number connection test(NCT)-A, NCT-B, digit symbol test(DST), line tracing test(LTT) and serial dotting test(SDT), and the scores were calculated. The total score of PHES <-4 was taken as the cut-off value for diagnosing MHE. Compare the differences in each subtest between MHE group and non-MHE group. Receiver operating characteristic curve(ROC) and area under the curve(AUC) was performed to assess the diagnostic value of independent and combined subtests in MHE. Mann-Whitney U test and DeLong test were used for statistical analysis. Results:A total of 581 patients with liver cirrhosis were enrolled, 457 were diagnosed as MHE, and the incidence of MHE was 78.7%. The results of NCT-A, NCT-B, SDT, LTT, DST of MHE group were 60.00 s(47.01 s, 88.00 s), 90.45 s(69.32 s, 125.35 s), 74.00 s(57.65 s, 96.60 s), 74.72(60.00, 98.61) and 27.00(20.00, 36.00), respectively. Compared those of non-MHE group(34.00 s(29.15 s, 44.48 s), 50.00 s(40.98 s, 60.77 s), 50.00 s(41.07 s, 63.03 s), 46.23(38.55, 59.42) and 42.00(34.00, 50.75)), the differences were statistically significant( Z=12.37, 12.98, 9.83, 11.56, 10.66; all P<0.001). The AUC(95% confidence interval(95% CI)) of subtests of PHES NCT-B, NCT-A, LTT, DST and SDT alone in MHE diagnosis were 0.880(0.849 to 0.910), 0.862(0.828 to 0.896), 0.838(0.799 to 0.877), 0.812(0.772 to 0.851) and 0.788(0.743 to 0.832), respectively. The combination of 2 PHES subtests significantly increased the diagnostic efficacy. Among them the diagnostic efficacy of the combination of NCT-B and LTT was the best, the AUC(95% CI) was 0.924(0.902 to 0.947), the specificity was 91.9% and the sensitivity was 79.2%, which was better than a single PHES subtest (NCT-A, NCT-B, SDT, LTT and DST) and the combination of NCT-A and DST(AUC was 0.879, 95% CI0.847 to 0.910) which was recommended by guidelines on the management of hepatic encephalopathy in cirrhosis, the differences were statistically significant ( Z=3.78, 3.83, 5.57, 5.51, 5.38, 2.93; all P<0.01). Furthermore, compared between the combination of NCT-B and LTT and the combination of 3 subests of PHES, only the diagnostic efficacy of combination of NCT-B, LTT and SDT (AUC was 0.936, 95% CI 0.916 to 0.956) was better than that of the combination of NCT-B and LTT, the difference was statistically significant( Z=2.32, P=0.020). Conclusion:Based on the diagnostic efficacy and clinical feasibility of PHES subtests and their combinations, the combination of NCT-B and LTT is recommended for the diagnosis of MHE.
9.Assessment of pathological biopsy and safety margin of specimens from breast cancer patients with breast conversing surgery
Jianke LYU ; Yiling YANG ; Li FU
Chinese Journal of Oncology 2021;43(8):817-820
Breast-conserving surgery (BCS) has now become one of the optimal surgical choices for early invasive breast cancer. The pathological diagnosis of margin in breast-conserving specimen is very important. There is no acknowledge on the approaches of pathological biopsy and safety margin diagnosis of breast conserving surgery. This paper will compare the biopsy and diagnosis methods of breast-conserving surgery specimens between Tianjin Medical University Cancer Institute and Hospital in China and MD Anderson Cancer Center in the United States. We summarize our biopsy method and diagnostic criteria to explore how to accurately evaluate the margin of breast-conserving surgery specimen from a pathological point of view, and to escort a successful breast-conserving surgery.
10.Assessment of pathological biopsy and safety margin of specimens from breast cancer patients with breast conversing surgery
Jianke LYU ; Yiling YANG ; Li FU
Chinese Journal of Oncology 2021;43(8):817-820
Breast-conserving surgery (BCS) has now become one of the optimal surgical choices for early invasive breast cancer. The pathological diagnosis of margin in breast-conserving specimen is very important. There is no acknowledge on the approaches of pathological biopsy and safety margin diagnosis of breast conserving surgery. This paper will compare the biopsy and diagnosis methods of breast-conserving surgery specimens between Tianjin Medical University Cancer Institute and Hospital in China and MD Anderson Cancer Center in the United States. We summarize our biopsy method and diagnostic criteria to explore how to accurately evaluate the margin of breast-conserving surgery specimen from a pathological point of view, and to escort a successful breast-conserving surgery.

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