1.Progress in regulation of macrophage function by bitter taste receptors and its mechanism
Lele WANG ; Yuzhen FANG ; Yuqing MA ; Zixi ZHAO ; Ruonan MA ; Xing WANG ; Yuxin ZHANG
Chinese Journal of Pathophysiology 2024;40(8):1520-1528
Bitter taste receptors,also known as type 2 taste receptors(T2Rs),are found not only in the mouth's taste bud cells but also in various tissues and cells,including macrophages.Macrophages,known for their re-markable plasticity,play a crucial role in regulating innate immunity,managing inflammation,and orchestrating immune responses to antigens,pathogens,and environmental factors.Recently,the study of the expression and function of bitter taste receptors within macrophages has garnered significant interest.This review summarizes the expression levels and dis-tribution characteristics of bitter taste receptors in macrophages and examines their effects on macrophage polarization,phagocytosis,and chemotaxis,as well as their potential molecular mechanisms.The purpose of this review is to provide in-sight and perspectives for research on the regulatory role of T2Rs in macrophage functions.
2.Oncogene goosecoid is transcriptionally regulated by E2F1 and correlates with disease progression in prostate cancer
Yue GE ; Sheng MA ; Qiang ZHOU ; Zezhong XIONG ; Yanan WANG ; Le LI ; Zheng CHAO ; Junbiao ZHANG ; Tengfei LI ; Zixi WU ; Yuan GAO ; Guanyu QU ; Zirui XI ; Bo LIU ; Xi WU ; Zhihua WANG
Chinese Medical Journal 2024;137(15):1844-1856
Background::Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer (PCa), the long tail of cancer genes remains to be defined. Goosecoid ( GSC) has been implicated in cancer development. However, the comprehensive biological role of GSC in pan-cancer, specifically in PCa, remains unexplored. The aim of this study was to investigate the role of GSC in PCa development. Methods::We performed a systematic bioinformatics exploration of GSC using datasets from The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, German Cancer Research Center, and our in-house cohorts. First, we evaluated the expression of GSC and its association with patient prognosis, and identified GSC-relevant genetic alterations in cancers. Further, we focused on the clinical characterization and prognostic analysis of GSC in PCa. To understand the transcriptional regulation of GSC by E2F transcription factor 1 ( E2F1), we performed chromatin immunoprecipitation quantitative polymerase chain reaction (qPCR). Functional experiments were conducted to validate the effect of GSC on the tumor cellular phenotype and sensitivity to trametinib. Results::GSC expression was elevated in various tumors and significantly correlated with patient prognosis. The alterations of GSC contribute to the progression of various tumors especially in PCa. Patients with PCa and high GSC expression exhibited worse progression-free survival and biochemical recurrence outcomes. Further, GSC upregulation in patients with PCa was mostly accompanied with higher Gleason score, advanced tumor stage, lymph node metastasis, and elevated prostate-specific antigen (PSA) levels. Mechanistically, the transcription factor, E2F1, stimulates GSC by binding to its promoter region. Detailed experiments further demonstrated that GSC acted as an oncogene and influenced the response of PCa cells to trametinib treatment. Conclusions::GSC was highly overexpressed and strongly correlated with patient prognosis in PCa. We found that GSC, regulated by E2F1, acted as an oncogene and impeded the therapeutic efficacy of trametinib in PCa.
3.Radiation shielding for the intraoperative radiotherapy using low energy X-rays
Daguang ZHANG ; Zixi ZHU ; Jiana SUN ; Yuan TIAN ; Wei WANG
Chinese Journal of Radiological Medicine and Protection 2022;42(8):629-635
Objective:To assess the shielding requirements of low energy X-ray intraoperative radiotherapy room under the domestic and foreign standards and guidelines, to measure the sured transmission factors for a range of shielding materials, the ambient dose equivalent rate around concerned positions and the shielding effect of protective devices, so as to provide references for shielding design of such radiotherapy units and applications of radiological protection devices.Methods:The required shielding thicknesses for a treatment room with INTRABEAM intraoperative radiotherapy system were calculated under the Chinese national standard GBZ 121, IPEM report No. 75 and NCRP report No. 151, respectively. The transmission factors for a range of shielding materials including solid water slab, shielding sheet and shielding apron were measured. Moreover, the ambient dose equivalent rates were measured under the simulated working conditions and the shielding effectiveness of a lead screen was evaluated.Results:The required lead thicknesses calculated under different standards and guidelines were less than 0.6 mm for all the concerned points, with the differences at sub-millimeter level. The low energy X-rays generated by this equipment attenuated rapidly in the shielding materials. The measured transmission factors of 0.05 mm lead equivalent shielding sheet and 0.25 mm lead equivalent shielding apron were 0.068 and 0.003 8, respectively. When the radiation was delivered using spherical applicator without any attenuation, the ambient dose equivalent rates at 1 m and 2 m from the X-ray source were 10.7 and 2.6 mSv/h, respectively. The corresponding measurement values decreased to 3.8 and 0.9 μSv/h, respectively, when the spherical applicator was inserted into a small water tank. Meanwhile, the ambient dose equivalent rate at 2 m was reduced to the background level when using protective screen.Conclusions:The shielding requirements for a low energy X-ray intraoperative radiotherapy facility are minimal, with low effective energy of X-rays generated by this equipment, but the dose rate close to the unshielded radiation source is high. The shielding scheme of treatment room should be optimized in design and the protective device should be used in a reasonable way.
4.Updates in diagnosis, treatment, and prevention of anaphylaxis to neuromuscular blocking agents and their antagonists
Zixi WANG ; Xu LI ; Xiuhua ZHANG ; Kai GUAN
Chinese Journal of Preventive Medicine 2022;56(6):740-747
Anaphylaxis to perioperative drugs has an insidious and rapid onset, can be life-threatening, and often results in the suspension of surgery. Neuromuscular blocking agents (NMBAs) are currently considered to be the most common cause of anaphylactic reactions among anesthetic drugs. With the increasing amount of anesthesia and surgery in the world, there are more and more NMBAs use, and the corresponding allergic risk is also increasing. With the use of NMBAs, their antagonists, such as neostigmine and sugammadex, are often used too, which have more and more allergy reports in clinical practice. Due to the complex mechanism of allergy caused by NMBAs and their antagonists, it is difficult to find out the culprit drug. The cross-reactivity between NMBAs is common, so it is often difficult to choose alternative drugs. This article summarized the epidemiology, pathological mechanisms, diagnostic methods and procedures, immediate treatment, and prevention strategies of anaphylaxis caused by these drugs.
5.Updates in diagnosis, treatment, and prevention of anaphylaxis to neuromuscular blocking agents and their antagonists
Zixi WANG ; Xu LI ; Xiuhua ZHANG ; Kai GUAN
Chinese Journal of Preventive Medicine 2022;56(6):740-747
Anaphylaxis to perioperative drugs has an insidious and rapid onset, can be life-threatening, and often results in the suspension of surgery. Neuromuscular blocking agents (NMBAs) are currently considered to be the most common cause of anaphylactic reactions among anesthetic drugs. With the increasing amount of anesthesia and surgery in the world, there are more and more NMBAs use, and the corresponding allergic risk is also increasing. With the use of NMBAs, their antagonists, such as neostigmine and sugammadex, are often used too, which have more and more allergy reports in clinical practice. Due to the complex mechanism of allergy caused by NMBAs and their antagonists, it is difficult to find out the culprit drug. The cross-reactivity between NMBAs is common, so it is often difficult to choose alternative drugs. This article summarized the epidemiology, pathological mechanisms, diagnostic methods and procedures, immediate treatment, and prevention strategies of anaphylaxis caused by these drugs.
6.Diagnostic accuracy and safety of Dermatophagoides pteronyssinus extracts used for skin prick test
Rui TANG ; Xiaohong LYU ; Yuxi LIU ; Ruiqi WANG ; Lianglu WANG ; Hong LI ; Jinlyu SUN ; Yuxiang ZHI ; Jianqing GU ; Kai GUAN ; Liping WEN ; Zixi WANG ; Lisha LI ; Le CUI ; Yingyang XU ; Junxiong ZHOU ; Tao XU ; Jia YIN
Chinese Medical Journal 2022;135(21):2563-2569
Background::Dermatophagoides pteronyssinus is a common allergen causing allergic diseases in China. The aim of this study was to evaluate the efficacy and safety of D. pteronyssinus extracts produced by Peking Union Medical College Hospital (PUMCH) for the skin prick test (SPT) in the diagnosis of D. pteronyssinus allergy. Methods::A total of 910 subjects with allergic diseases were prescribed D. pteronyssinus SPT and specific sIgE (sIgE) test among the Outpatients of Department of Allergy, PUMCH from August 10, 2015 to August 30, 2017. Receiver operating characteristic curve (ROC) analysis was performed according to the results of D. pteronyssinus-sIgE detection. The accuracy of D. pteronyssinus extracts used for SPT in the diagnosis of D. pteronyssinus allergy was evaluated under different cutoff values. Adverse events after SPT were recorded to evaluate safety. Results::There were 796 and 618 subjects in the full analysis set (FAS) and the per protocol set (PPS), respectively. The areas under the curve of FAS and PPS were 0.871 and 0.873, respectively. According to the ROC of PPS, the optimal and 95% specificity diagnostic cutoff values of D. pteronyssinus SPT mean wheal diameter were 3.25 and 3.75 mm, respectively. No adverse events occurred. Conclusion::The extracts of D. pteronyssinus for SPT were simple, highly accurate, and safe and should be considered for recommendation in the clinical diagnosis of D. pteronyssinus allergy.
7.Diagnosis progress in component-resolved diagnostics of food allergy
Zixi WANG ; Jinlyu SUN ; Lianglu WANG
Chinese Journal of Applied Clinical Pediatrics 2021;36(12):897-901
IgE-mediated food allergy is a common health problem worldwide, and the incidence of food allergy in China is also increasing gradually in the past decades.However, the traditional diagnostic measurements for food allergen specific IgE (sIgE) are based on the in- vivo or in- vitro tests of the intact allergen extracts, with low specificity and sensitivity, as well as limited diagnostic information.Therefore, the clinical diagnosis of food allergies often requires an oral food challenge test, which increases the suffering and risk of patients.Along with the development of component-resolved diagnostics (CRD) of food allergy, the sIgE against a single allergenic component can be measured quantitatively, thus generating the concept of " CRD" , which makes food allergy diagnosis more accurate and helps people distinguish cross allergens, determine the severity of the disease and the risk of severe allergic reactions, and predict the efficacy of immunotherapy.Besides, the diagnostic accuracy would be enhanced significantly and the reliance on oral food challenge tests would be reduced.In this review, the new progress in the diagnosis of common food allergen components would be summarized, and the advantages of CRD would be discussed.
8.Optimized strategy of anesthesia for thoracoscopic pulmonary surgery: erector spinae plane block with high volume of ropivacaine combined with general anesthesia
Guihuan CHEN ; Zixi GONG ; Qiuguo WANG ; Xin WANG ; Sa PENG ; Hui LI
Chinese Journal of Anesthesiology 2021;41(6):699-702
Objective:To evaluate the optimized efficacy of erector spinae plane block (ESPB) with high volume of ropivacaine combined with general anesthesia for patients undergoing thoracoscopic pulmonary surgery.Methods:Sixty American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients of both sexes, aged 18-64 yr, with body mass index of 18-24 kg/m 2, scheduled for elective thoracoscopic pulmonary surgery, were divided into 2 groups ( n=30 each) using a random number table method: ESPB with high volume (40 ml) of 0.4% ropivacaine combined with general anesthesia group (E40 group) and ESPB with conventional volume (20 ml) of 0.4% ropivacaine combined with general anesthesia group (E20 group). Ultrasound-guided ESPB was performed on the operated side before general anesthesia induction in both groups.In E40 group, 0.4% ropivacaine 40 ml was injected.In E20 group, 0.4% ropivacaine 20 ml was injected.Total intravenous anesthesia was applied in both groups.Sufentanil was used for patient-controlled intravenous anesthesia (PCIA) after the end of operation.The PCIA pump was set up with a 2 ml bolus dose (0.04 μg/kg), a 10 min lockout interval and background infusion at a rate of 0.05 μg·kg -1·h -1.The analgesia lasted for 48 h after operation, and the numeric rating scale (NRS) score was maintained ≤ 3.When NRS score ≥ 4, morphine 5 mg was intravenously injected for rescue analgesia.The onset time of block, intraoperative consumption of propofol and remifentanil, time to first pressing the analgesia pump, the first requirement for morphine and the ratio of patients using morphine within 48 h after surgery were recorded.The cumulative consumption of requirement for opioids (effective pressing dose of analgesic pump+ consumption of requirement for morphine) within 12, 24, 36 and 48 h after surgery and satisfaction with analgesia were recorded.The extubation time, length of ICU stay, the first postoperative off-bed time, the chest tube removal time and duration of stay in hospital were recorded.The incidence of intraoperative adverse events (hypertension and hypotension) and postoperative adverse events (dizziness, nausea and vomiting) were recorded. Results:Compared with E20 group, the onset time of block was significantly shortened, the cumulative consumption of requirement for opioids within 24, 36 and 48 h after surgery was decreased, the ratio of paitents using morphine within 48 h after surgery was decreased, time to first pressing the analgesia pump and the first requirement for morphine were prolonged, satisfaction with analgesia score was increased, and the first postoperative off-bed time and the chest tube removal time were shortened in group E40 ( P<0.05). There was no significant difference in the incidence of adverse events between the 2 groups ( P>0.05). Conclusion:Compared with ESPB with the conventional volume of ropivacaine combined with general anesthesia, ESPB with the high volume of ropivacaine combined with general anesthesia can reduce the postoperative consumption of opioids, and prolong the duration of effective analgesia, which are helpful for postoperative rapid recovery without increasing the development of adverse events in patients undergoing thoracoscopic pulmonary surgery.
9.Prevalence situation and risk factors related to acne in adult woman
Zixi WANG ; Qi WANG ; Fei LI ; Ying FAN ; Shiqin TAO
Chinese Journal of Medical Aesthetics and Cosmetology 2021;27(2):133-138
Objective:To determine the prevalence situation of adult female acne (AFA) patients and to explore the risk factors related to AFA.Methods:From September 2019 to June 2020, 290 female acne patients aged from 25 to 48 (29.57±4.50) years were surveyed with a questionnaire of risk factors and the prevalence situation of acne in the acne clinic of the Department of Dermatology, Wuxi No.2 Hospital Affiliated with Nanjing Medical University.Results:AFA occured more frequently in the jaw (95.17%), cheek (93.79%) and forehead (89.66%). Recurrent acne (38.62%) and comedonal acne (50.34%) more commonly occured. Cosmetics, endocrine, diet, genetics and other factors aggravated AFA. Age ( H=7.286, P>0.05; F=0.122, P>0.05), gonadal hormone concentrations ( Z=-0.365, P>0.05; χ 2=0.276, P>0.05), menstrual cycle ( Z=-0.274, P>0.05; χ 2=0.217, P>0.05), genetics ( Z=-1.244, P>0.05; χ 2=1.771, P>0.05) made no difference to acne grading and types. Excessive use of cosmetics could lead to increased comedo (χ 2=7.097, P<0.05). Cosmetics had no difference to acne grading ( Z=-0.065, P>0.05). Gonadal hormone concentrations were uncorrelated with menstrual cycle (χ 2=1.397, P>0.05). Conclusions:The pathogenesis of AFA is related to a variety of factors, which affect the skin barrier function and require comprehensive treatment.
10.The effect on patient life quality of prophylactic treatment to seasonal allergic rhinitis and related transcriptomics research
Lisha LI ; Kai GUAN ; Junda LI ; Zixi WANG ; Le CUI ; Yingyang XU
Chinese Journal of Preventive Medicine 2021;55(5):606-612
Objective:The preseason prophylactic treatment of seasonal allergic rhinitis (AR) caused by pollens could alleviate AR symptoms during the pollen season. This study aimed to evaluate the effect of prophylaxis usage of suplatast tosilate on the life quality of AR patients in the pollen season, and investigate the potential mechanism of action through transcriptomic analysis.Methods:This is a randomized controlled study. AR patients allergic to weed pollens were recruited from Allergy Clinic of Peking Union Medical College Hospital from January 2020 to June 2020, and divided into prophylactic group who started to take suplatast tosilate as prophylaxis 2 weeks before the spread of weed pollens[n=10, 4 men and 6 women with age range of (34±6) years old] and control group who did not use any prophylactic treatment[n=24, 12 men and 12 women with age range of (33±9) years old]. The differences of age ( t=0.381, P=0.706) and gender ( χ2=0.595, P=0.715) distribution between the patients of two groups were not statistically significant. All the subjects filled in the rhinoconjunctivitis quality of life questionnaire (RQLQ) while onset of AR symptoms, and peripheral blood was drawn for transcriptomic analysis 1 month before and during the pollen season. Differences between groups were statistically analyzed through chi-square test and t test. Results:There was no significant difference in visual analogue scale of rhinitis symptom in the last pollen season between prophylactic group and control group[ 8.0 (6.4, 9.3) vs 7.3 (6.1, 8.0), Z=1.180, P=0.254]. The RQLQ score of prophylactic group was superior to that of control group in the weed pollen season (2.9±0.9 vs 3.7±0.9, t=-2.438, P=0.026). 210 differentially expressed genes of fold change ≥2 were identified, with 147 genes upregulated and 63 genes downregulated in the prophylactic group compared to the control group. Gene Ontology annotation showed that IL-12 and IL-23 related pathways were downregulated in prophylactic group ( P=0.006 48). Polymerase Chain Reaction (PCR) verification of differentially expressed genes indicated that the relative expression level of HLA-G in prophylactic group was significantly lower than that in control group (0.23±0.19 vs 1.00±0.49, t=4.016, P=0.006). Conclusion:The prophylactic treatment of suplatast tosilate showed some benefit to the life quality of seasonal AR patients during the pollen season, and the potential mechanism might be related with the downregulation of IL-12 and IL-23 pathways and decreased expression of HLA-G.

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