1.Mechanism prediction and experimental verification of Maxing Shigan Decoction against influenza A virus infection based on UPLC-MS/MS and network pharmacology
Jiawang HUANG ; Jianing SHI ; Yang LIU ; Zhiying FENG ; Jingmin FU ; Siyu WANG ; Xuan JI ; Rong YU ; Ling LI
Digital Chinese Medicine 2025;8(4):532-542
Objective:
To investigate the chemical compositions of Maxing Shigan Decoction (麻杏石甘汤, MXSGD) and elucidate its anti-influenza A virus (IAV) mechanism from prediction to validation.
Methods:
Ultra high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was employed to analyze the chemical compositions of MXSGD. Network pharmacology theories were used to screen and identify shared targets of both the potential targets of active ingredients of MXSGD and IAV. A protein-protein interaction (PPI) network was then constructed, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The binding stability between core bioactive compounds and key targets was validated by molecular docking and dynamic simulations. A total of 24 BALB/c mice were infected with IAV to build IAV mouse models. After successful modelling, the mouse models were randomly divided into model, MXSGD high-dose (2.8 g/kg), MXSGD low-dose (1.4 g/kg), and oseltamivir (20.14 mg/kg) groups, with an additional normal mice as control group (n = 6 per group). The treatments were administered by gavage daily between 8:00 a.m. and 10:00 a.m. for five consecutive days. Upon completion of the administration, the body weight ratio, lung index, protein content in the bronchoalveolar lavage fluid (BALF), and the levels of inflammatory factors including interleukin (IL)-6 and tumor necrosis factor (TNF)-α in mice were measured to preliminarily analyze the therapeutic efficacy of MXSGD against IAV infection. Furthermore, the expression levels of mechanistic target of rapamycin (mTOR), hypoxia inducible factor (HIF)-1α, and vascular endothelial growth factor (VEGF) proteins in the HIF-1 signaling pathway, which was enriched by network pharmacology, were detected by Western blot.
Results:
A total of 212 chemical components in MXSGD were identified by the UPLC-MS/MS method. These chemical components can be classified into 9 primary categories and 31 secondary categories. After intersecting the chemical component targets with IAV-related targets, a total of 567 potential MXSGD components targeting IAV were identified. The construction of PPI network and the results of both GO and KEGG enrichment analyses revealed that the anti-IAV effects of MXSGD were associated with multiple pathways, including apoptosis, TNF, HIF-1, and IL-17 signaling pathways. The results of molecular docking demonstrated that the binding energies between the core compound 1-methoxyphaseollin and key targets including HIF-1α, mTOR, and VEGF were all lower than – 5.0 kcal/mol. Furthermore, molecular dynamics simulations confirmed the structural stability of the resulting complexes. Animal experiments showed that compared with the normal controls, IAV-infected mice showed significantly reduced body weight ratio, markedly increased lung index, protein content in BALF, and the levels of inflammatory factors such as IL-6 and TNF-α (P < 0.01), thereby causing damage to the lung tissue; consequently, the expression levels of mTOR, HIF-1α, and VEGF proteins in the lung tissues of these mice were significantly elevated (P < 0.01). However, after MXSGD treatment, the mouse models presented a significant increase in body weight ratio, as well as marked decreases in lung index, protein content in BALF, and the levels of inflammatory factors including IL-6 and TNF-α (P < 0.01). Furthermore, the therapy alleviated IAV-induced injuries and significantly downregulated the expression levels of mTOR, HIF-1α, and VEGF proteins in lung tissues (P < 0.01 or P < 0.05).
Conclusion
MXSGD exerts anti-IAV effects through multi-component, multi-target, and multi-pathway synergism. Among them, 1-methoxyphaseollin is identified as a potential key component, which alleviates virus-induced lung injury and inflammatory response via the regulation of HIF-1 signaling pathway, providing experimental evidence for the clinical application of MXSGD.
2.Exploration of the Disease Mechanism and Treatment of Colorectal Cancer Based on the "One Qi Circulation"
Zhiying WANG ; Ling XU ; Jialin YAO ; Jiajun SONG ; Yun LI ; Shujuan FU ; Yabin GONG ; Yi ZHONG
Journal of Traditional Chinese Medicine 2024;65(10):1068-1071
Based on the theory of "one qi circulation" founded by HUANG Yuanyu, the core disease mechanism of colorectal cancer is the innate spleen deficiency and stomach qi failing to bear downward, which leads to the turbidity assemble in large intestine, forming the carcinoma toxin, and ultimately transforms into colorectal cancer. The treatment should base on recovering the circulation of qi, Huangya Decoction (黄芽汤) as the basic formula, the circulation of qi ascending and descending as the base, adjusting ascending and descending together with Xiaqi Decoction (下气汤), and differentiating the syndrome on yin-yang excess-deficiency; for spleen-kidney yang deficiency syndrome, treated with Tianhun Decoction (天魂汤) to supplement liver, kidney and assist yang; for liver-kidney yin deficiency syndrome, treated wtih Dipo Decoction (地魄汤) to supplement lung, kidney, and assist yang. They jointly prompt one qi circulation to provide the thoughts for the treatment of colorectal cancer by traditional Chinese medicine.
3.Efficacy and safety assessment of transnasal nebulisation of budesonide in children with adenoid hypertrophy.
Wenxin CHEN ; Zhiying ZHOU ; Jiahua SHEN ; Zhiyi WANG ; Yong FU
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2024;38(12):1154-1160
Objective:To investigate the efficacy and assess the safety of transnasal nebulisation of budesonide in children with adenoid hypertrophy. Methods:Children with adenoid hypertrophy who attended the Children's Hospital of Zhejiang University School of Medicine between December 2021 and December 2022 were randomly assigned to budesonide high-dose group(Group A: budesonide 1 mg/dose + saline nasal rinse), budesonide low-dose group(Group B: budesonide 0.5 mg/dose + saline nasal rinse), and control group(Group C: saline nasal rinse), and each group 20 children were collected separately, The efficacy and safety of transnasal nebulisation of budesonide in children with adenoid hypertrophy were assessed by comparing the symptomatic VAS scores, adenoidal nasopharyngeal lateral radiographs A/N values, nocturnal sleep oximetry(SaO2), and the incidence of adverse events during the treatment period of 8-week in the three groups. Results:The 8-week baseline differences in adenoid A/N values were statistically different between groups A and B(P<0.001) and A and C(P=0.022), with the reduced amount in adenoid volume being most pronounced in group A, which differed from the other two groups. With the increase of intervention time, SaO2 levels gradually increased(F=154.725, P<0.001) and VAS scores gradually decreased(F=165.616, P<0.001) in all three groups. After 8 weeks of treatment, there was no statistically significant difference in SaO2 level(P=0.085) between groups A and B. There was a statistically significant difference in VAS total scores between Group A and Group B (P < 0.05) . The improvement of SaO2and total VAS score in group A was higher than that in group B. There was a statistically significant difference in the comparison of SaO2 level and total VAS score between groups A and B, and between groups A and C(P<0.01); after the intervention of the three groups, showing the greatest improvement of total VAS score and SaO2in the group A, followed by Group B. There was no statistically significant difference in the incidence of adverse events among Groups A, B, and C throughout the trial. Conclusion:The treatment of children with adenoid hypertrophy by intranasal nebulisation of budesonide suspension has good efficacy and safety, which is conducive to reducing the size of adenoids, improving the clinical symptoms of children with adenoid hypertrophy, and improving the SaO2of nocturnal sleep, and it has a certain clinical application value.
Humans
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Budesonide/administration & dosage*
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Adenoids
;
Child
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Male
;
Female
;
Hypertrophy
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Nebulizers and Vaporizers
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Treatment Outcome
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Administration, Intranasal
;
Child, Preschool
4.Impacts of transmembrane serine protease 4 expression on susceptibility to severe acute respiratory syndrome coronavirus 2.
Qi TAN ; Jiewen FU ; Zhiying LIU ; Haoyue DENG ; Lianmei ZHANG ; Jiayue HE ; Xiaotao LI ; Junjiang FU
Chinese Medical Journal 2023;136(7):860-862
Humans
;
SARS-CoV-2
;
COVID-19
5.Effects of fasudil hydrochloride on ROCK2 protein and ferroptosis in hippocampus during early brain injury in rats with subarachnoid hemorrhage
Linlin SUN ; Zhiying LI ; Xingxiang ZHANG ; Zehong XU ; Baiqiang WU ; Tiantian WANG ; Xinge XU ; Aijun FU
Chinese Journal of Behavioral Medicine and Brain Science 2023;32(1):9-14
Objective:To investigate the effects of fasudil hydrochloride(FH) on Rho-associated kinase 2(ROCK2) protein and ferroptosis in hippocampal area during early brain injury in rats with subarachnoid hemorrhage(SAH).Methods:Total 36 SPF grade Sprague-Dawley rats were divided into 3 groups by random number table method: Sham group, SAH group and SAH+ FH (a ROCK2 protein inhibitor) group (FH goup) with 12 rats in each group.SAH animal model was established by internal carotid artery perforation.The rats in FH group were injected intraperitoneally with FH(15 mg/kg) 30 minutes after successful modeling, and rats in Sham group and SAH group were injected intraperitoneally with the same volume of 0.9% sodium chloride solution.Twenty-four hours after the intervention, shuttle box test was used to observe the learning and memory ability of rats.The Fe 2+ content in rat hippocampus tissue was detected by colorimetry, and the protein levels of ROCK2 and ferroptosis-related long-chain acyl-CoA synthetase 4(ACSL4) and glutathione peroxidase 4(GPX4) in hippocampus were detected by immunohistochemistry and Western blot.Statistical analysis was performed by SPSS 20.0 software.One-way ANOVA was used for multigroup comparison, and LSD test was used for further pairwise comparison. Results:(1)In the shuttle box test, there were statistically significant differences in the number of avoidance reactions and avoidance reaction time of rats among the three groups( F=20.348, 22.316, both P<0.05). The number of avoidance reaction in SAH group was less than that in Sham group ((17.92±2.94) times, (27.13±3.48) times, P<0.05), the time of avoidance reaction in SAH group was longer than that in Sham group ((9.15±2.87) s, (3.68±1.09) s, P<0.05), while the number of avoidance reaction in FH group ((21.63±4.11) times) was more than that in SAH group, and the time of avoidance reaction ((6.08±1.76) s) was shorter than that in SAH group (both P<0.05). (2) The colorimetry results showed that there was a statistically significant difference in the content of Fe 2+ in hippocampus of rats among the three groups( F=7.965, P<0.05). The Fe 2+ content in SAH group was significantly higher than that of Sham group((0.091±0.032) nmol/mg, (0.038±0.024) nmol/mg, P<0.05), and the Fe 2+ content in the FH group ((0.065±0.021) nmol/mg) was lower than that of SAH group ( P<0.05). (3) There were significant differences in the number of ROCK2, ACSL4 and GPX4 positive cells in hippocampus of rats among the three groups in immunohistochemistry ( F=7.602, 14.171, 36.077, all P<0.05). The positive cells of ROCK2 and ACSL4 in SAH group ((21.63±4.72), (55.13±19.41)) were significantly higher than those of Sham group ((11.63±3.62), (23.38±3.74)) (both P<0.05), and the positive cells of ROCK2 and ACSL4 in FH group ((15.88±6.64), (44.75±8.29)) were both lower than those of SAH group(both P<0.05), while the number of GPX4 positive cells in SAH group (25.38±6.30) was significantly lower than that of Sham group (60.25±10.36) ( P<0.05), and the number of GPX4 positive cells in FH group (45.13±7.51) was higher than that of SAH group( P<0.05). (4)The results of Western blot showed that there were significant differences in the expression levels of ROCK2, ACSL4 and GPX4 proteins in the hippocampus of rats among the three groups( F=4.812, 12.573, 10.849, all P<0.05). The protein expression levels of ROCK2 and ACSL4 in SAH group were significantly higher than those in Sham group(both P<0.05), and the protein expression levels of ROCK2 and ACSL4 in FH group were lower than those in SAH group (both P<0.05), while the expression level of GPX4 protein in SAH group (0.27±0.09) was significantly lower than that in Sham group( P<0.05), and the expression level of GPX4 protein in FH group was higher than that of SAH group ( P<0.05). Conclusion:FH can inhibit ferroptosis in the hippocampus and improve the learning and memory ability of rats, and the mechanism may be related with down-regulation of ROCK2 protein.
6.Piriform sinus hamartoma in children: a case report and literature review.
Zhiying ZHOU ; Wenxin CHEN ; Jia LIU ; Yong FU
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2023;37(12):964-971
Objective:To investigate the clinical manifestations and treatment of laryngopharynx hamartoma in children. Methods:The clinical data of a child with piriform sinus hamartoma treated in our hospital were analyzed retrospectively. The age, gender, clinical manifestations, auxiliary examination, location of the tumor and surgical methods were analyzed. Results:The patient had a good prognosis after surgery, and no tumor recurrence was found after 1 year of follow-up. Conclusion:Laryngopharynx hamartoma is rare in children. It should be considered in children with laryngeal dysfunction and upper airway obstruction. Complete resection of the tumor is the key to postoperative recurrence.
Child
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Humans
;
Hamartoma/surgery*
;
Larynx/pathology*
;
Neoplasm Recurrence, Local/pathology*
;
Pyriform Sinus/pathology*
;
Retrospective Studies
;
Male
;
Female
7.Innovative Teaching of "Doctor-patient" Friendly Model for Diabetes from the Perspective of Deep Blended Learning
Chinese Medical Ethics 2023;36(6):693-697
The teaching of diabetes has always been the focus and difficulty of clinical internal science teaching. How to skillfully integrate theoretical knowledge into clinical practice and help students deeply master medical knowledge and clinical skills is a topic that clinical teaching teachers are considering. Under the background of analyzing the concept and connotation of deep blended learning, this paper constructed the diabetes "doctor-patient" friendly model teaching process in the perspective of deep blended learning from the three stages of "learning situation analysis and independent learning" in the early stage, "ability improvement and in-depth research" in the middle stage, and "reflection and ability expansion" in the later stage. This paper expounded the positive role of the "doctor-patient" friendly model of diabetes in clinical teaching from three main aspects: improving the integration effect of theory and practice, fully meeting students’ learning needs, and increasing the connection between doctors, patients, and students.
8.Exploration and practice of constructing a risk-based quality management model for clinical trials
Zhiying FU ; Shuhua ZHAO ; Xiaohong LIU ; Yannan YUAN ; Min JIANG
Chinese Journal of Medical Science Research Management 2022;35(5):379-384
Objective:To conduct a quantitative and qualitative analysis of the issues found in quality management, establish a risk-based whole-process quality management model, and improve the quality of clinical trials.Methods:Based on the risk-based quality management theory, the issues found in the quality control of drug clinical trials in Beijing Cancer Hospital in 2020 were structured and classified by severity (mild to moderate to severe) and 10 categories, and the risk matrix was graded by a semi-quantitative method. Targeted quality control strategies for different levels of risk were carried out according to visual analysis of the informative quality analysis platform. Chi-square tests of the severity of quality control issues in our hospital in 2020 and 2021 and non-parametric tests of the number of issues per capita in each category were used to evaluate the effectiveness of the management model.Results:A risk matrix was established according to the severity and frequency of the issues found in the quality control in 2020. The issues with severe risks were categorized as protocol compliance and serious adverse events, and categories with moderate risks included informed consent, biological sample related, original records, and investigator folders. After using visual analysis and adopting the risk-based quality control strategy, the proportion of severe issues found in quality control in our hospital in 2021 was 0.92%, lower than that of 1.39% in 2020, and the difference was statistically significant. The average number of issues detected per capita in each category for each trial in 2021 was lower than that in 2020 with a statistical difference, indicating that the management model was effective.Conclusions:Using information technology to adopt risk-based quality management is helpful to improve the quality of hospital clinical trials.
9.Prevalence and risk factors of depression among middle school students in Tianjin in 2019 -2020
Zhiying SUN ; Zhonghui LIU ; Ke XYU ; Baojia FENG ; Gang FU ; Changchun HOU
Journal of Public Health and Preventive Medicine 2022;33(4):152-155
Objective To investigate the prevalence and risk factors of depression among middle school students in Tianjin , and to provide the evidence for making targeted prevention of depression. Methods In September 2019 and September 2020, the stratified cluster sampling method was used to select 32 380 middle school students in Tianjin for face-to-face questionnaire survey, which included the basic information , depressive symptoms , health status , life and behavior habits , injuries , and Internet addiction in the previous week. The χ2 test , t test, univariate and multivariate logistic stepwise regression were used to analyze the data. Results From 2019 to 2020, the prevalence of depression among middle school students in Tianjin was 20.48% , with higher prevalence in girls than in boys and higher prevalence in urban areas than in suburban areas. Multivariate regression results show that smoking, school bullying, parental abuse, Internet addiction , injury , urban area , female , sickness, anemia and sweets are risk factors for depression ; fruits , vegetables , breakfast , high Intensive exercise are protective factors. The OR ( 95%CI ) of depression of school bullying and parental beating and scolding were 4.71 ( 95%CI 3.84 -5.79) and 2.94 ( 95%CI 2.72 - 3.18); the OR ( 95%CI ) of depression of internet addiction students was 2.76 ( 95%CI 2.30 - 3.11); the OR ( 95%CI ) of depression in anemia students was 1.68 ( 95%CI 1.36 - 2.07); compared with non-smokers, the odd ratio(OR) ( 95%CI ) of depression for smoking less than 1 cigarette, 1-11 cigarette, and 11-20 cigarette per day were 1.83 ( 95%CI 0.75 - 2.44), 1.64 ( 95%CI 0.94 -2.84 ), 1.92 ( 95%CI 1.51 - 2.44), respectively; Conclusion The depression level of middle school students in Tianjin is in the middle, and the intervention should be interfered from many aspects, such as cultivating students' good living behavior habits and healthy body, providing good family atmosphere and campus environment.
10.Analysis of risk factors in early infection patients after heart transplantation
Yunfei LIU ; Xiangli ZHANG ; Zhiying LI ; Zhikun FU ; Keke LIANG ; Lin GUO
Chinese Journal of Organ Transplantation 2022;43(7):406-411
Objective:To explore the risk factors of early infection patients after heart transplantation(HT)and provide references for preventing and treating early infection.Methods:From April 2018 to May 2021, clinical data were retrospectively reviewed for 95 HT recipients treated at Zhengzhou Seventh People's Hospital.They were divided into two groups of infected(n=34)and uninfected(n=61). Gender, age, disease type, preoperative IABP implantation, postoperative intra-aortic balloon pump(IABP)implantation, postoperative extracorporeal membrane oxygenation(ECMO)implantation, preoperative mechanical ventilation, preoperative leukocyte, preoperative lymphocyte, preoperative serum C-reactive protein(CRP), operative approach, APACHEⅡscore, NYHA grade, hemoglobin, cardiopulmonary bypass time, donor heart cold ischemia time, postoperative thoracic drainage tube indwelling time, postoperative gastric tube indwelling time, postoperative urinary tube indwelling time, postoperative acute rejection, postoperative ventilator assisted treatment time and postoperative ICU time.The risk factors of early infection were analyzed by univariate and multivariate Logistic regression analysis.Results:There were 34 cases of early infection after HT and 8 cases died.In infection group, preoperative hemoglobin(female <110 g/L or male <120 g/L), ECMO post-operation, 24-48 h post-operation, APACHE post-operation(>6), postoperative intrathoracic drainage tube indwelling time(≥7 d), postoperative gastric tube indwelling time(≥4 d), postoperative urinary tube indwelling time(≥5 d), postoperative acute rejection(positive), postoperative ventilator assisted treatment time(≥2 d)and postoperative ICU time(≥10 d)were 18 cases(52.94%), 8(23.53%), 30(88.24%), 22(64.71%), 18(52.94%), 20(58.82%), 4(11.76%), 21(61.76%)and 19(55.88%); uninfected group: 16 cases(26.23%), 3(4.92%), 32(52.46%), 24(39.34%), 15(24.59%), 31(34.43%), 1(1.64%), 21(34.43%)and 4(6.56%). Significant inter-group differences existed( χ2=6.778, 5.68, 12.326, 5.623, 7.740, 5.297, 4.489, 6.615, 28.947, P<0.05). Multivariate Logistic regression analysis indicated that 24-48h post-operation, APACHEⅡ score >6(β=1.024, Wald χ2=7.653, OR=2.141, OR95% CI=1.323~4.215), ECMO post-operation(β=1.783, Wald χ2=6.186, OR=5.949, OR95% CI =1.459~24.25), postoperative intrathoracic drainage tube indwelling time ≥7 d(β=0.712, Wald χ2=5.745, OR=1.054, OR95% CI=1.183~6.753), postoperative gastric tube indwelling time(β=0.832, Wald χ2=6.756, OR=1.132, OR95% CI=1.416~8.406), postoperative ventilator assisted treatment time(β=0.745, Wald χ2=6.563, OR=1.212, OR95% CI=1.289~7.346)and postoperative ICU time=1.28(β=1.325, Wald χ2=9.752, OR=2.435, OR95% CI=1.426~6.354)were independent risk factor for early infection after HT( P<0.05). Conclusions:Early infection after HT remains higher.It is significantly correlated with 24-48 h post-operation APACHE II score, ECMO post-operation, postoperative intrathoracic drainage tube indwelling time, postoperative gastric tube indwelling time, postoperative ventilator assisted treatment time and postoperative ICU time.Targeted interventions should be adopted for lowering the incidence of early infection after HT.


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