1.The Influence of Shoutai Wan (寿胎丸) on Lactic Acid Content at the Maternal-Fetal Interface and Expression of Immune-Related Factors in Recurrent Miscarriage Model Mice
Jingfang LYU ; Min JIANG ; Zhenzhen ZHOU ; Li ZHANG ; Shuhui WANG ; Dandan LI ; Yajing SONG ; Huilan DU
Journal of Traditional Chinese Medicine 2024;65(9):934-942
ObjectiveTo explore the possible mechanisms of Shoutai Wan (寿胎丸) in treating recurrent miscarriage (RSA) from the perspective of immune tolerance under the acidic microenvironment at the maternal-fetal interface. MethodsFemale CBA/J mice were randomly divided into normal group, model group, progesterone group, and Shoutai Wan group, with 15 mice in each group. The mice in the normal group and model group were given 0.2 ml distilled water by gavage each day, the Shoutai Wan group given Shoutai Wan decoction 0.15 g/(10 g·d) by gavage, the progesterone group given progesterone tablets 0.44 mg/(10 g·d) by gavage. After gavage for 14 days, the mice were cohabited. Female CBA/J mice in the normal group were mated with male BALB/c mice at a ratio of 2∶1, and female CBA/J mice in the other groups were mated with male DBA/2 mice at a ratio of 2∶1 to establish the RSA mouse model. Vaginal smears were taken from the female mice the next morning, and the appearance of a large number of spermatozoa and the presence of a vaginal plug were considered as the first day of pregnancy. After the appearance of the plug, the mice were continued to be administered according to the previous method until the 10th day of pregnancy. On the 10th day of pregnancy, maternal-fetal interface tissues were collected from each group of mice, and lactate dehydrogenase colorimetric method was used to detect lactate (LA) content; qPCR method and Western blot method were used to detect the expression of immune-related factors interleukin-4 (IL-4), interferon-gamma (IFN-γ), transforming growth factor beta 1 (TGF-β1), and forkhead box protein 3 (Foxp3) mRNA and protein; flow cytometry was used to detect the numbers of helper T lymphocyte 1 (Th1), helper T lymphocyte 2 (Th2), regulatory T cell (Treg), classical macrophage (M1), and alternative macrophage (M2). The bivariate Pearson test was used to analyze the correlation between LA content and the numbers of Th1, Th2, Treg, M1, and M2 cells, as well as the correlation between LA content and the expression of IL-4, IFN-γ, TGF-β1, Foxp3 protein, and mRNA. ResultsOn the 10th day of pregnancy, compared with the normal group, the LA content decreased in the model group, and the expression of IL-4, TGF-β1, Foxp3 protein and mRNA in the maternal-fetal interface tissues decreased, while the expression of IFN-γ protein and mRNA increased. The numbers of Th1 and M1 cells increased, while the numbers of Th2, Treg, and M2 cells decreased (P<0.05 or P<0.01). Compared with the model group, the LA content increased in the Shoutai Wan group and progesterone group. The expression of IL-4, TGF-β1, Foxp3 protein and mRNA in the maternal-fetal interface tissues increased, while the expression of IFN-γ protein and mRNA decreased. The numbers of Th1 and M1 cells decreased, while the numbers of Th2, Treg, and M2 cells increased (P<0.05 or P<0.01). The LA content was positively correlated with the numbers of Th2, Treg, and M2 cells, and the expression of IL-4, TGF-β1, Foxp3 protein, and mRNA (P<0.05 or P<0.01); the LA content was negatively correlated with the numbers of Th1, M1 cells, and the expression of IFN-γ protein and mRNA (P<0.05 or P<0.01). ConclusionShoutai Wan may improve immune tolerance by regulating the expression of immune-related factors in the acidic microenvironment at the maternal-fetal interface of RSA model mice, thereby exerting its role in preventing miscarriage.
2.Clinical Validation of a Prototype Smart Non-Invasive Pregnancy Glucose Monitor
Heqing LU ; Lirui CHENG ; Qiaoling DU ; Xiaofeng ZHANG ; Zhenzhen SUN ; Zhigang ZHU
Chinese Journal of Medical Instrumentation 2024;48(5):539-543
The aim of this study is to evaluate the effectiveness of a smart non-invasive blood glucose monitor prototype during pregnancy through clinical validation.The monitor utilizes near-infrared spectroscopy combined with AI big data analysis of photoelectric volumetric pulse wave data to achieve non-invasive monitoring of blood glucose in women during pregnancy.The research team developed a monitor that employs a sensing chip,effectively overcoming the problems of weak signals and individual differences in non-invasive blood glucose monitoring.The user experience is enhanced by visualizing the test results on the accompanying cell phone APP(application)of the smart non-invasive pregnancy blood glucose monitor.Clinical validation revealed that the non-invasive monitoring data for pregnant women aged 20~30 years significantly differed from those obtained via traditional blood glucose measurement methods,whereas no significant difference(P<0.05)was observed for pregnant women aged 31~42 years.The study concluded that further calibration of the monitor and an expansion of the sample size are necessary to enhance consistency with invasive glucose monitoring results.
3.Immunomodulatory activity of macrophage trained induced by Streptococcus plur-animalium
Xinyi DU ; Yu GAO ; Xueyue LUO ; Yongjun YANG ; Zhenzhen LIU
Chinese Journal of Veterinary Science 2024;44(8):1645-1650
This experiment aims to screen and isolate bacteria for the domestication of macrophages and to identify their domestication effector molecules.Bacteria were isolated and purified from cow and sheep feces.The procedures included preparing fermentation supernatant and conducting ex-periments with a mouse peritoneal macrophage model.Nitric oxide(NO)levels were measured,tumor necrosis factor-alpha(TNF-α)was analyzed using ELISA,the domestication activity was e-valuated by mouse peritoneal macrophage model.The activated bacteria were subjected to 16S rRNA gene sequences identification,growth curves determination,and saturated ammonium sul-fate precipitation for NO assay and ELISA analysis of TNF-α to assess the phagocytic capability of domesticated macrophages against Staphylococcus aureus.One strain,ED-8,with immunomodula-tory polarizing properties was successfully isolated.Alignment of its 16S rRNA gene sequence showed 99.86%similarity with Streptococcus zooepidemicus,classifying it as such species.The fermentation supernatant significantly stimulated NO and TNF-a secretion in macrophages.The phagocytic capability against Staphylococcus aureus of macrophages polarized by ED-8 also en-hanced.This effect was retained after crude extraction,indicating the presence of immunomodula-tory activity.In this study,multiple animal chain streptococcus ED-8 was successfully isolated.Its secreted products were shown to induce the trained immunity of macrophages,enhancing their phagocytic activity.
4.Preliminary exploration of the effectiveness of comprehensive healthcare management model for children with bacterial meningitis after discharge
Shijie LI ; Gang LIU ; Wanxia ZHANG ; Huili HU ; Ming ZHAO ; Zhenzhen DOU ; Wenjing JI ; Juan DU ; Aimin LIANG
Chinese Journal of Health Management 2024;18(10):761-767
Objective:To explore the effectiveness of the comprehensive healthcare management model for children with bacterial meningitis after discharge.Methods:This study was a retrospective cohort study that included 268 children with bacterial meningitis who were discharged from the infectious medicine ward of Beijing Children′s Hospital from September 2018 to September 2023. The children were managed with a multidisciplinary collaborative comprehensive healthcare management model after discharge. Outpatient data at 1 month and 6, 12 and 24 months after discharge were collected, including (height, weight, body mass index, nutritional feeding status, hearing and vision screening results, Gesell developmental assessment results and intervention guidance services. The follow-up interval or frequency was dynamically adjusted or increased according to the child′s situation. The paired sample t-test and chi square test were applied to compare the differences in Gesell developmental quotient (DQ) and developmental delay rate between the first and last assessments to preliminarily explore the effectiveness of the comprehensive healthcare management model for children with bacterial meningitis after discharge. Results:All the 268 children completed their first assessment one month after discharge, and 37 children were found to have abnormal physical growth, mainly obesity (28 children), and another 9 children were malnutrition. Nutritional intervention and feeding guidance services were provided to all the 37 children, and as of the last follow-up, 20 children′s physical growth evaluations had turned normal. A total of 188 children completed at least 2 developmental assessments, with an interval of (14.2±9.4) months between the first and last assessments (range: 3.1-49.5 months). The DQ values of in the energy region of adaptability, gross motor skills, fine motor skills, language, and personal social skills at the last assessment were significantly higher than those at the first assessment [(91.93±13.28) vs (80.73±15.96) points, (91.69±12.96) vs (78.31±16.58) points, (89.32±16.11) vs (80.68±15.63) points, (90.10±16.65) vs (82.04±18.43) points, (92.01±14.05) vs (77.82±17.42) points]; moreover, the rates of developmental delay in each energy region were significantly lower than those at the initial assessment (9.6% vs 35.1%, 9.6% vs 42.0%, 18.1% vs 33.0%, 13.3% vs 31.9%, 9.6% vs 42.0%) (all P<0.05). Among the 200 children who completed the hearing screening, 18 were found with hearing abnormalities, and 2 were diagnosed with hearing loss in the Otolaryngology Department. Among 217 children who completed vision screening, 23 had abnormalities, and 5 were diagnosed with ophthalmic abnormalities in Ophthalmology Department (2 with strabismus, 2 with refractive errors, and 1 with optic nerve injury). Two children were found to have autism-like behavior during monitoring, and were referred to a developmental behavior clinic to be diagnosed with autism spectrum disorder and were given early diagnosis and intervention guidance. Conclusion:The comprehensive healthcare management model for children with bacterial meningitis after discharge can integrate clinical and healthcare resources, which is beneficial for improving the prognosis and enhancing the quality of life for children with special health status.
5.Erratum: Author correction to "Identification of anthelmintic parbendazole as a therapeutic molecule for HNSCC through connectivity map-based drug repositioning" Acta Pharm Sin B 12 (2022) 2429-2442.
Dong LIANG ; Chen YU ; Zhao MA ; Xingye YANG ; Zhenzhen LI ; Xuhui DONG ; Xiaojun QIN ; Lupei DU ; Minyong LI
Acta Pharmaceutica Sinica B 2024;14(11):5089-5090
[This corrects the article DOI: 10.1016/j.apsb.2021.12.005.].
6.Effect of simultaneous integrated boost intensity-modulated radiation therapy on lateral lymph node metastasis in rectal cancer
Jinxia SHEN ; Dexi DU ; Huijuan HE ; Ming LI ; Zhenzhen ZHOU ; Shubo DING
Chinese Journal of Radiological Medicine and Protection 2023;43(11):866-872
Objective:To evaluate the efficacy and safety of simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT) for rectal cancer with lateral lymph node metastasis (LLNM).Methods:From January 2016 to December 2022, 103 rectal cancer patients with LLNM were enrolled. The patients were divided into SIB-IMRT group (52 cases) and conventional chemoradiotherapy (CRT) group (51 cases) using the random number table method. The dose was 50 Gy for the pelvis with 60 Gy of SIB-IMRT for the LLNM in the SIB-IMRT group. The dose was 50 Gy for the pelvis in the CRT group. The primary endpoint was the lateral recurrence rate. The efficacy and adverse reactions of the two groups were compared.Results:The adverse reactions and surgical complications after neoadjuvant radiotherapy were comparable between the two groups. The response rates of LLNM treatment were 76.9% and 56.9%, respectively, in the two groups ( χ2=4.69, P=0.03). The SIB-IMRT group and CRT group had a local recurrence rate of 7.7% and 25.5% ( χ2=5.92, P=0.015), respectively, and a lateral recurrence rate of 3.8% and 23.5% ( χ2=8.49, P=0.004), respectively. Univariate analysis showed that the SIB-IMRT, short axis of lateral lymph nodes <5 mm after radiotherapy, and negative result in the postoperative lymph node pathological examination were factors associated with lateral recurrence. Multivariable regression analysis demonstrated that the SIB-IMRT ( HR=6.42, 95% CI: 1.40-29.49) and short axis of lateral lymph nodes <5 mm after radiotherapy ( HR=0.17, 95% CI: 0.04-0.66) were independent factors associated with lateral recurrence. The two groups had a 3-year disease-free survival of 73.25% and 62.6% ( P>0.05), respectively, and a 3-year overall survival of 87% and 82.5% ( P>0.05), respectively. Conclusions:The SIB-IMRT is safe and effective for rectal cancer with LLNM. The short axis of lateral lymph nodes <5 mm after neoadjuvant radiotherapy and SIB-IMRT is an independent risk factor for lateral recurrence.
7.Clinical and electro-physiological characteristics of reflex epilepsy induced by thinking activities
Zhenzhen DU ; Jinxiang WANG ; Wanying XU ; Ze CHEN ; Zezhi WANG ; Yonghong LIU
Chinese Journal of Neurology 2022;55(9):1002-1007
Objective:To explore the clinical and electro-physiological characteristics of reflex epilepsy induced by thinking activities.Methods:Five patients of reflex epilepsy induced by thinking activities during electroencephalogram (EEG) monitoring in the EEG Monitoring Center, Department of Neurology, Xijing Hospital,the Air Force Military Medical University from January 2017 to September 2019 were studied and followed up.Results:All the 5 patients are male, aged 14 to 33 years, with the disease course of 3 to 9 years and the follow-up of 1 to 4 years. The myoclonic jerks, spasms seizure and generalized tonic and clonic seizure occured to the 5 patients. The EEG background of low amplitude alpha rhythm was recorded in the 5 patiens. The ictal-EEG of 2 cases showed the spike wave or spike slow complex waves in the central, parietal area, and the ictal-EEG of 1 case showed the generalized spike-wave discharge. There were no seizures occuring to the 2 cases during video-electroencephalography monitoring. There were no abnormalities in cranial magnetic resonance imaging. The arterial spin labeling of 2 cases suggested that the right cerebral hemisphere cerebral blood flow was lower than contralateral. Antiseizure drugs (levetiracetam in 4 cases and levetiracetam+magnesium valproate in 1 case) were administered, 4 cases were seizure free and 1 case was uncontrolled.Conclusions:The reflex epilepsy induced by thinking activities is common in young men, and the EEG background with low amplitude alpha rhythm may be the characteristic of the reflex epilepsy induced by thinking activities. The levetiracetam may be the good choice for the reflex epilepsy induced by thinking activities and the prognosis of reflex epilepsy induced by thinking activities is good.
8.Therapeutic effect of artificial liver multi-mode sequential combination in patients with hepatitis B virus-related acute-on-chronic liver failure
Xueshi ZHOU ; Tingting SU ; Hejuan DU ; Xiaoye GUO ; Sen WANG ; Chao LI ; Ying ZHANG ; Yuanwang QIU ; Zhenzhen DONG ; Xia WANG ; Xiaoyan SHI
Chinese Journal of Infectious Diseases 2022;40(12):722-728
Objective:To explore the therapeutic effect of multi-mode sequential combination of artificial liver in the treatment of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF).Methods:The clinical data of HBV-ACLF patients treated with artificial liver in Wuxi Fifth People′s Hospital from January 2018 to June 2021 were retrospectively analyzed. Eighty-six patients were divided into artificial liver multi-mode sequential combination therapy group (sequential combination group) and conventional treatment group. The cytokine level changes and model for end-stage liver disease (MELD) score were analyzed at 14 days of disease duration. The survival outcome and complications of artificial liver were analyzed after 30 days of follow-up. Two independent samples t test and chi-square test were used for statistical analysis. Cox regression analysis was used to analyze the risk factors of death, and Kaplan-Meier method was used to analyze the survival rate of patients. Results:A total of 86 patients were enrolled, including 48 patients in sequential combination group with the average number of artificial liver of 4.68 times/person, and 38 patients in conventional treatment group with the average number of artificial liver of 3.17 times/person. At 14 days of disease duration, interleukin (IL)-6, IL-8, interferon γ-inducible protein (IP)-10 level and MELD score in sequential combination group decreased significantly than those in the conventional treatment group ( t=3.80, 3.62, 4.95 and 1.11, respectively, all P<0.050). After 30 days of follow-up, 63 patients survived and 23 patients died. Cox regression analysis showed that baseline international normalized ratio (hazard ratio ( HR)=0.558, 95% confidence interval ( CI) 0.193 to 0.856, P=0.027), baseline antithrombin Ⅲ activity ( HR=0.876, 95% CI 0.824 to 0.932, P<0.001), artificial liver mode ( HR=0.819, 95% CI 0.236 to 0.992, P=0.005), spontaneous peritonitis ( HR=0.170, 95% CI 0.045 to 0.647, P=0.009) and hepatic encephalopathy ( HR=0.004, 95% CI 0.001 to 0.030, P<0.001) were independent influencing factors for 30-day survival outcome. The cumulative survival rate of sequential combination group was higher than that of conventional treatment group, and the difference was statistically significant ( χ2=5.45, P=0.020). There were no significant differences in the proportions of bleeding, deep vein thrombosis, heart rate and blood pressure instability between the two groups ( χ2=0.63, 1.20 and 0.54, respectively, all P>0.050). The platelet decline of patients in sequential combination group was slighter than that in conventional treatment group, and the difference was statistically significant ( t=-4.17, P=0.002). Conclusions:Multi-mode sequential combination therapy of artificial liver could eliminate cytokines and reduce MELD score more effectively in patients with HBV-ACLF, and prolong the survival time of patients and have little effect on platelet count.
9.Identification of anthelmintic parbendazole as a therapeutic molecule for HNSCC through connectivity map-based drug repositioning.
Dong LIANG ; Chen YU ; Zhao MA ; Xingye YANG ; Zhenzhen LI ; Xuhui DONG ; Xiaojun QIN ; Lupei DU ; Minyong LI
Acta Pharmaceutica Sinica B 2022;12(5):2429-2442
Head and neck squamous cell carcinoma (HNSCC) is one of the most common human cancers; however, its outcome of pharmacotherapy is always very limited. Herein, we performed a batch query in the connectivity map (cMap) based on bioinformatics, queried out 35 compounds with therapeutic potential, and screened out parbendazole as a most promising compound, which had an excellent inhibitory effect on the proliferation of HNSCC cell lines. In addition, tubulin was identified as a primary target of parbendazole, and the direct binding between them was further verified. Parbendazole was further proved as an effective tubulin polymerization inhibitor, which can block the cell cycle, cause apoptosis and prevent cell migration, and it exhibited reasonable therapeutic effect and low toxicity in the in vivo and in vitro anti-tumor evaluation. Our study repositioned an anthelmintic parbendazole to treat HNSCC, which revealed a therapeutic utility and provided a new treatment option for human cancers.
10.The protective effect of Zhicao Tea Mixture on Müller cells and the expression of inflammatory factors in mice with diabetic retinopathy
Manhui ZHU ; Yuanyuan TU ; Zhenzhen WANG ; Jingxia DU ; Yang GUO ; Jiaowen XU ; E SONG
Chinese Journal of Ocular Fundus Diseases 2020;36(4):302-307
Objective:To observe the protective effect of Zhicao Tea Mixture on Müller cells and the expression of inflammatory factors in mice with diabetic retinopathy.Methods:Seventy-five C57BL/6J mice were randomly divided into the normal control group, diabetes mellitus (DM) group, low concentrations group, medium concentrations group and high concentrations group, with 16 mice in each group. The diabetes model of mice in all groups except the normal control group were established by intraperitoneal injection of STZ (60 mg/kg). Four weeks after the successful modeling, the Zhicao Tea Mixture with low (30 ml/kg), medium (60 ml/kg) and high concentrations (120 ml/kg) were respectively administered by gavage. Weight and blood glucose of mice in each group were measured every two weeks. After 8 weeks, Western blot method was used to detect the mice retina Müller cells activation marker gelatinous fibrous acidic protein (GFAP). Immunofluorescence was performed to detect the expression GFAP and glutamine synthetase (GS). Real-time quantitative PCR (RT- qPCR) and ELISA were used to determine the mRNA and protein expression levels of mouse retinal VEGF, TNF-α, IL-1β and IL-6 respectively.Results:The weight of mice in the DM group was lower than that of the normal control group, and the blood glucose was increased. Zhicao Tea Mixture had no effect on the weight of DM mice, but had a significant hypoglycemic effect. The GFAP expression ( t=38.318, P<0.001) in the retina of mice in the DM group was increased and GS expression ( t=29.737, P<0.001) was decreased compared with the control group. The GFAP expression ( t=13.677, 19.387, 16.305; P<0.05) in the retina of mice in the low, medium and high concentrations group were decreased and GS expression ( t=5.170, 19.399, 6.705; P<0.05) were increased compared with the DM group. The expressions of retinal inflammatory factors VEGF, TNF-α, IL-1β and IL-6 in DM group all increased, while the expressions of the above-mentioned inflammatory factors in the retina of mice decreased in the low, medium and high concentrations group. Conclusion:Zhicao Tea Mixture can decrease the blood glucose of DM mice and reduces the diabetic retinal inflammatory response.

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