1.Transient Formation of Stress Granules Disturbs Neural Stem Cell Differentiation.
Mengmeng WANG ; Yarong WANG ; Hongyu MA ; Hanze LIU ; Yating LU ; Yaozhong ZHANG ; Zhihui HUANG ; Songqi DONG ; Kun ZHANG ; Shengxi WU ; Yazhou WANG
Neuroscience Bulletin 2025;41(11):2078-2082
2.A cisplatin prodrug-based self-assembling ozone delivery nanosystem sensitizes radiotherapy in triple-negative breast cancer.
Tianyue XU ; Dan ZHENG ; Meixu CHEN ; Linlin SONG ; Zhihui LIU ; Yan CHENG ; Yujie ZHAO ; Liwen HUANG ; Yixuan LI ; Zhankun YANG ; Cong LI ; Biao DONG ; Jing JING ; Hubing SHI
Acta Pharmaceutica Sinica B 2025;15(5):2703-2722
Lacking therapeutic targets highlights the crucial roles of chemotherapy and radiotherapy in the clinical management of triple-negative breast cancer (TNBC). To relieve the side effects of the chemoradiotherapy combination regimen, we design and develop a self-assembled micelle nanosystem consisting of perfluorocarbon chain-modified cisplatin prodrug. By incorporating perfluorodecalin, this nanosystem can effectively carry ozone and promote irradiation-derived reactive oxygen species (ROS) production. By leveraging the perfluorocarbon sidechain, the nanosystem exhibits efficient internalization by TNBC cells and effectively escapes from lysosomal entrapment. Under X-ray irradiation, ozone-generated ROS disrupts the intracellular redox balance, thereby facilitating the release of cisplatin in a reduction-responsive manner mediated by reduced glutathione. Moreover, oxygen derived from ozone decomposition enhances the efficacy of radiotherapy by alleviating tumor hypoxia. Notably, the combination of irradiation with ozone-loaded cisplatin prodrug nano system synergistically prompts antitumor efficacy and reduces cellular/systemic toxicity in vitro and in vivo. Furthermore, the combo regimen remodels the tumor microenvironment into an immune-favored state by triggering immunogenic cell death and relieving hypoxia, which provides a promising foundation for a combination regimen of immunotherapy. In conclusion, our nanosystem presents a novel strategy for integrating chemotherapy and radiotherapy to optimize the efficacy and safety of TNBC clinical treatment.
3.Exploring the etiology,pathogenesis,and treatment methods of depression with somatization disorder from the perspective of"cold water,damp earth,and stagnant wood"
Zhihui LIU ; Hongxin ZHENG ; Baozhao JU ; Ye DONG ; Xue GONG ; Siyuan DING
Journal of Beijing University of Traditional Chinese Medicine 2025;48(10):1345-1351
Depression is primarily characterized by persistent low mood,emotional disorders,and loss of interest.Somatization disorder is a type of neurotic disorder,primarily featuring recurrent,varied,and non-organic physical discomfort symptoms.In traditional Chinese medicine,depression with somatization disorder can be classified under the category of"depression"and"hysteria"according to its clinical symptoms.This article focuses on the dynamic evolution of the functions of the kidney,spleen,and liver,and explains the core pathogenesis of depression with somatization disorder based on the theory of"cold water,damp earth,and stagnant wood"proposed by HUANG Yuanyu.It explores the causes and related manifestations.Symptoms mainly characterized by cramps and convulsions can be attributed to the liver;symptoms primarily characterized by heaviness,distension,and dull pain accompanied by weakness can be attributed to the spleen;symptoms primarily characterized by stiffness,reluctance to move or inability to move,and reluctance to extend outward can be attributed to the kidney.Liver depression and spleen dampness,as well as wood depression and earth congestion,are treated by strengthening the spleen and soothing the liver,drying dampness and calming wind,and the modified Xiaoyao Powder combined with Yueju Pill is recommended.Spleen dampness and kidney coldness,earth failure and water overflow,are treated by tonifying the spleen and kidney,warming water and transforming dampness,and the modified Jingui Shenqi Pill combined with Linggui Zhugan Decoction is recommended.Kidney coldness and liver hyperactivity,water not nourishing wood,are treated by warming the kidney and enriching essence,replenishing water and nourishing wood,and the modified Dihuang Yinzi is recommended.This article explores the corresponding etiology,pathogenesis,treatment methods,and prescriptions for depression with somatization disorder,with the aim of providing new insights for clinical diagnosis and treatment.
4.Establishment and evaluation of a Nomogram early prediction model for severe dengue fever
Li LIU ; Hongjun LI ; Lixian CHANG ; Hui CHEN ; Zhihui MA ; Zhijian DONG ; Lingjun SHEN ; Chunyun LIU
Chinese Journal of Endemiology 2025;44(3):179-185
Objective:To analyze the influencing factors of severe dengue fever patients in the early stage, construct a early prediction model for severe dengue fever, and evaluate it.Methods:A retrospective analysis was conducted to collect early clinical data of dengue fever patients admitted to the People's Hospital of Mengla County and the Third People's Hospital of Kunming in Yunnan Province from July to December 2023. The multifactor logistic regression was used to analyze the factors affecting the severe dengue fever patients, and Nomogram prediction model was used for visualization. Receiver operating characteristic (ROC) curve and calibration curve analysis were used to evaluate the model.Results:A total of 534 dengue fever patients were included, including 291 males and 243 females, aged (39.95 ± 15.69) years. Among them, there were 59 cases (11.05%) of severe dengue fever. The results of multifactor logistic regression analysis showed that age ( OR = 1.05, 95% CI: 1.02 - 1.08, P < 0.001), cardiovascular disease ( OR = 5.28, 95% CI: 2.08 - 13.40, P < 0.001), serous effusion ( OR = 4.34, 95% CI: 1.63 - 11.57, P = 0.003), aspartate aminotransferase ( OR = 1.03, 95% CI: 1.02 - 1.04, P < 0.001), lactate dehydrogenase ( OR = 1.00, 95% CI: 1.00 - 1.01, P = 0.001), and fibrinogen ( OR = 0.46, 95% CI: 0.28 - 0.76, P = 0.003) were independent influencing factors in the early stage of severe dengue fever. The area under the ROC curve of the Nomogram prediction model constructed from the above six variables was 0.96 (0.93 - 0.98). The calibration curve analysis results showed that the mean absolute error between the predicted values of the Nomogram prediction model and the actual observed values was 0.014. Conclusions:Age, cardiovascular disease, serous effusion, aspartate aminotransferase, lactate dehydrogenase, and fibrinogen are independent influencing factors in the early stage of severe dengue fever. The Nomogram prediction model established based on these variables has good predictive ability for severe dengue fever.
5.Molecular epidemiology and genetic characteristics of human metapneumovirus in Suzhou
Xuan YUAN ; Zefeng DONG ; Zhihui XU ; Xuerong YA ; Qiang SHEN
Chinese Journal of Microbiology and Immunology 2025;45(10):826-831
Objective:To analyze the epidemiological characteristics of human metapneumovirus(hMPV)in respiratory samples from patients in Suzhou,China,and investigate the results of whole-genome sequencing,so as to provide scientific evidence for a deeper understanding of its genetic diversity and the development of preventive measures.Methods:In this study,1 340 influenza-like illness(ILI)samples and 970 severe acute respiratory infection(SARI)samples were collected from two sentinel hospitals in Suzhou in 2024. Nucleic acid detection was performed using a multiplex real-time fluorescence PCR method. For hMPV-positive samples,whole-genome sequencing was conducted on the Illumina Miseq platform. Mutations,insertions,deletions,and other variations were identified using the pathogenic virus whole-genome analysis system. A phylogenetic tree was constructed by the Maximum Likelihood method for lineage analysis.Results:Among 2 310 respiratory samples,the overall hMPV positivity rate was 1.69%(39/2 310),with positivity rates of 1.27%(17/1 340)in ILI samples and 2.27%(22/970)in SARI samples. No statistically significant difference was observed between the two groups( P>0.05). The proportion of mixed infections in hMPV-positive samples was 46.15%(18/39),with mixed infection rates of 23.53%(4/17)in the ILI group and 63.64%(14/22)in the SARI group. In terms of temporal distribution,the peak period of hMPV infection primarily concentrated in January and December. The whole genomes of 13 hMPV strains were successfully obtained,and 554 missense mutations were identified in the coding region,with particularly significant variations observed in the G gene region. Phylogenetic analysis revealed that 4 strains belonged to the A2b2 subtype,while 9 strains belonged to the B2 subtype. Conclusions:In Suzhou,hMPV exhibits a relatively balanced distribution between ILI and SARI clinical groups,with infection peaks mainly occurring in winter and a high proportion of mixed infections. The predominant circulating strain is the B2 subtype,and its genome shows significant genetic variation,particularly in the G gene region.
6.Mechanisms of FLASH irradiation on acute radiation-induced intestinal injury in mice
Xiaoman LIU ; Yani LIU ; Zhihui LI ; Dongfei YAN ; Lihui ZHANG ; Menghua LI ; Shaobin LI ; Guofu DONG ; Changzhen WANG
Chinese Journal of Radiological Medicine and Protection 2025;45(11):1085-1091
Objective:To explore differences in the radiation-induced intestinal injury in mice exposed to ultra-high dose rate (FLASH) and conventional-dose-rate (CONV) pulsed X-ray irradiation in order to provide evidence for the application of ultra-high dose rate pulsed X-rays in gastrointestinal radiotherapy.Methods:Using the random number table method, 32 C57BL/6J mice were randomly divided into four groups: a sham irradiation group (SHAM), two conventional dose rate groups (CONV0.067 and CONV0.1), and an ultra-high dose rate group (F215), with each group containing eight mice. All groups, except SHAM, received a single 12 Gy abdominal X-ray irradiation at dose rates of 0.067, 0.1, and 215 Gy/s, respectively. At 3 d post-irradiation, histopathological (hematoxylin-eosin staining, HE staining), immunohistochemical, and Western blot analysis were performed to assess the histopathological markers and oxidative stress indicators of intestinal tissues, as well as relevant proteins involved in signaling pathways.Results:At 3 d post-irradiation, mice in all irradiation groups suffered from varying degrees of intestinal tissue degeneration and necrosis, epithelial cell shedding, villus shortening, and crypt loss ( t = 5.75, 8.79, 5.71, P < 0.05). Regarding oxidative stress, at 3 d post-irradiation, mice in the CONV0.067 and CONV0.1 groups showed significantly lower levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX), glutathione (GSH), and total antioxidant capacity (T-AOC) compared to those in the F215 group ( t = 7.06-10.64, P < 0.01). In contrast, their malondialdehyde (MDA) levels were significantly elevated ( t = 11.06, 8.31, P < 0.01), with no statistical significance observed between them and mice in the F215 group ( P > 0.05). Immunohistochemical and Western blot analyses indicated that at 3 d post-irradiation, mice in the three irradiation groups exhibited an upward trend in the Nrf2 and HO-1 protein levels and a downward trend in the Keap1 protein level compared to those in the SHAM group. Notably, statistical significance was observed between the F215 group and the two conventional dose rate groups ( t = 4.89-20.95, P < 0.05). These result were consistent with the prior changes in antioxidant markers. Conclusions:Ultra-high-dose-rate X-ray irradiation reduces acute RIII by alleviating oxidative stress and modulating the expression of the Keap1-Nrf2-HO-1 signaling pathway.
7.Methods and application effects of simultaneous correction of sunken upper eyelid during double eyelid plasty
Zhihui DAI ; Lei WU ; Sen HAI ; Bin DONG ; Chong LIN ; Lulu ZHANG ; Li ZHAO
Chinese Journal of Plastic Surgery 2025;41(9):951-960
Objective:To investigate the method and clinical efficacy of simultaneous correction of sunken upper eyelid during double eyelid plasty.Methods:A retrospective analysis was conducted on patients with single eyelids and sunken upper eyelid treated at the Department of Plastic Surgery, the First People’s Hospital of Zhengzhou, from October 2022 to February 2024. All patients underwent incisional double eyelid plasty with individualized correction based on depression severity. For mild depression, a combination of pretarsal orbicularis oculi muscle flap folding and orbital septum fat flap transposition was performed for correction. For moderate depression, additional autologous stromal vascular fraction (SVF)-gel grafting would be performed if residual depression persisted after the aforementioned approach. For severe depression, if the orbital fat was sufficient, the orbicularis oculi muscle flap folding, orbital fat flap repositioning and autologous SVF-gel transplantation were used. If there was insufficient orbital fat, the correction involved the use of a orbicularis oculi muscle flap and SVF-gel transplantation. Postoperative follow-up was conducted regularly, and related complications were statistically analyzed. Six months after the surgery, two blinded plastic surgeons evaluated outcomes via visual analog scale (VAS), including five aspects: symmetry of palpebral folds(including width and curvature of the double eyelid fold), fold contour, depression improvement, scar quality, overall eyelid aesthetics. Each aspect was rated on a scale from 1 to 10, with higher scores indicating better outcomes. Patient satisfaction was scored separately (1-5 per item), with higher scores indicating greater satisfaction.Results:A total of 64 patients were enrolled, including 4 males and 60 females; the age ranged from 19 to 66 years[ (32.0±9.7) years]. The degree of sunken upper eyelid was mild in 33 cases, moderate in 19 cases and severe in 12 cases. All patients underwent double eyelid plasty and orbicularis oculi flap folding. Based on this, 45 cases (33 mild and 12 moderate cases) underwent orbital septum fat flap transposition, 11 severe cases underwent SVF-gel grafting, and 8 cases (7 moderate and 1 severe cases) required combined approaches to correct depression. During the procedure, 19 cases (38 sides) received (1.8±0.8) ml of SVF-gel injection. Among these cases, one case with severe sunken upper eyelid who did not receive orbital fat transfer was injected with high density fat (left side: 0.6 ml, right side: 0.8 ml) due to insufficient SVF-gel volume. Two cases with severe sunken upper eyelid who only had autologous SVF-gel transplantation did not fully correct the depression within 3 months post-surgery received a second SVF-gel injection[(1.0±0.1) ml]. Follow-up was conducted for 6 to 12 months after surgery. All patients experienced varying degrees of eyelid edema, which typically lasted 2 to 3 months. Ecchymosis (34 sides), conjunctival congestion (3 sides), and temporary ptosis (5 sides) all resolved within 2 weeks. Pigmentation (14 sides) and scar hyperplasia (3 sides) disappeared or stabilized within 6 months. No patients developed complications such as incision infection, hematoma, fat liquefaction, local skin unevenness, or induration. The surgeons’ VAS scores of the above five indicators were all > 8 points, and the satisfaction scores of patients for the five indicators were all > 4 points. In both scoring, the improvement of sunken upper eyelid scored the highest, which were (9.2 ± 0.9) points and (4.8 ± 0.6) points respectively.Conclusion:For patients with single eyelids and varying degrees of sunken upper eyelid, performing double eyelid plasty and orbicularis oculi muscle flap folding, individualized correction is achieved through autologous fat redistribution techniques, based on the severity of the sunken upper eyelid and the amount of orbital fat. This single procedure can restore upper eyelid volume and rejuvenate the appearance, resulting in a natural and aesthetically pleasing double eyelid with minimal complications and high patient satisfaction.
8.Literature case analysis of fetal/neonatal toxicity caused by maternal exposure to angiotensin receptor blockers in the second and third trimesters of pregnancy
Zhihui MA ; Dong FU ; Ligang JI
Adverse Drug Reactions Journal 2025;27(2):107-114
Objective:To explore the adverse effects of maternal exposure to angiotensin receptor blockers (ARBs) during the second and third trimesters of pregnancy on the fetus/neonate.Methods:Relevant databases at home and abroad were searched (up to April 2024), and case reports of ARB exposure during the second and third trimesters of pregnancy were collected. Data such as patient age, ARB drugs exposed to and the gestational age, concomitant drugs, maternal amniotic fluid examination, and fetal/neonatal outcomes were extracted from the literature. Descriptive statistical analysis was conducted on the information of ARB exposure during pregnancy.Results:A total of 37 case reports were included, describing the outcomes of 55 fetuses/neonates (including a pair of twins) exposed to ARBs in utero during the second and third trimesters of pregnancy of 54 pregnant women. Six kinds of ARBs were involved in the 54 pregnant women, including valsartan (31.5%, in 17 women), candesartan (25.9%, in 14 women), losartan (22.2%, in 12 women), olmesartan (11.1%, in 6 women), telmisartan (5.6%, in 3 women), and irbesartan (3.7%, in 2 women); 49 women (90.7%) took above ARBs continuously form pre-pregnancy or the first trimester of pregnancy to the second and third trimesters of pregnancy, which were mostly prescribed by non-obstetricians (internal medicine or general practice). In the 54 pregnant women, 46 had amniotic fluid examination during pregnancy, of which 45 (97.8%) had oligohydramnios or absence of amniotic fluid; 4 voluntarily induced labor to terminate pregnancy, and 50 reported the natural outcome of pregnancy and had 51 fetuses/newborns, 15 (29.4%) of which died in utero or within 1 week after birth, and 36 (70.6%) of which were discharged alive. Among the newborns, 81.3% (39/48) were premature infants, and 74.4% (32/43) were low birth weight infants. In the 55 fetuses/newborns, 48 (87.3%) had varying degrees of disease and developmental defects. The most commonly involved organ or system was kidney [72.7% (40/55)], and the major pathological change was renal tubular dysplasia; the following injury was lung/respiratory diseases and dysplasia with an incidence of [41.8% (23/55)], which was the main cause of fetal/neonatal death. Subsequently, abnormal development of skull/brain and limbs/hands and feet, abnormal circulatory system, abnormal coagulation, retinopathy, etc. have also been reported.Conclusion:ARBs exposure during the second and third trimesters of pregnancy poses significant risks to the fetus/neonate, often leading to developmental defects of renal tubular, lung, skull/brain, and limbs, and even death.
9.Literature case analysis of fetal/neonatal toxicity caused by maternal exposure to angiotensin receptor blockers in the second and third trimesters of pregnancy
Zhihui MA ; Dong FU ; Ligang JI
Adverse Drug Reactions Journal 2025;27(2):107-114
Objective:To explore the adverse effects of maternal exposure to angiotensin receptor blockers (ARBs) during the second and third trimesters of pregnancy on the fetus/neonate.Methods:Relevant databases at home and abroad were searched (up to April 2024), and case reports of ARB exposure during the second and third trimesters of pregnancy were collected. Data such as patient age, ARB drugs exposed to and the gestational age, concomitant drugs, maternal amniotic fluid examination, and fetal/neonatal outcomes were extracted from the literature. Descriptive statistical analysis was conducted on the information of ARB exposure during pregnancy.Results:A total of 37 case reports were included, describing the outcomes of 55 fetuses/neonates (including a pair of twins) exposed to ARBs in utero during the second and third trimesters of pregnancy of 54 pregnant women. Six kinds of ARBs were involved in the 54 pregnant women, including valsartan (31.5%, in 17 women), candesartan (25.9%, in 14 women), losartan (22.2%, in 12 women), olmesartan (11.1%, in 6 women), telmisartan (5.6%, in 3 women), and irbesartan (3.7%, in 2 women); 49 women (90.7%) took above ARBs continuously form pre-pregnancy or the first trimester of pregnancy to the second and third trimesters of pregnancy, which were mostly prescribed by non-obstetricians (internal medicine or general practice). In the 54 pregnant women, 46 had amniotic fluid examination during pregnancy, of which 45 (97.8%) had oligohydramnios or absence of amniotic fluid; 4 voluntarily induced labor to terminate pregnancy, and 50 reported the natural outcome of pregnancy and had 51 fetuses/newborns, 15 (29.4%) of which died in utero or within 1 week after birth, and 36 (70.6%) of which were discharged alive. Among the newborns, 81.3% (39/48) were premature infants, and 74.4% (32/43) were low birth weight infants. In the 55 fetuses/newborns, 48 (87.3%) had varying degrees of disease and developmental defects. The most commonly involved organ or system was kidney [72.7% (40/55)], and the major pathological change was renal tubular dysplasia; the following injury was lung/respiratory diseases and dysplasia with an incidence of [41.8% (23/55)], which was the main cause of fetal/neonatal death. Subsequently, abnormal development of skull/brain and limbs/hands and feet, abnormal circulatory system, abnormal coagulation, retinopathy, etc. have also been reported.Conclusion:ARBs exposure during the second and third trimesters of pregnancy poses significant risks to the fetus/neonate, often leading to developmental defects of renal tubular, lung, skull/brain, and limbs, and even death.
10.Bibliometric analysis of researches on glucocorticoids use in systemic lupus erythematosus from 2004 to 2024
Jie BAI ; Liming DONG ; Zhihui SONG ; Jiawei WANG
Chinese Journal of Pharmacoepidemiology 2025;34(7):815-823
Objective To conduct a visual analysis of the research hotspots and trends of glucocorticoids in the treatment of systemic lupus erythematosus(SLE)both domestically and internationally.Methods The relevant literature from 2004 to 2024 on glucocorticoids use in SLE were retrieved in Web of Science,CNKI,WanFang Data and VIP databases.CiteSpace 6.3.R6 software was used to conduct bibliometric analysis of the number of publications,authors,research institutions,and keywords,and to draw knowledge maps.Results A total of 4,124 literature were retrieved,and 1,491 English literature and 593 Chinese literature were screened and included.The overall trend of English publications was increasing,while the number of Chinese publications declined in recent years.China is the most active country in this research field,but the research among authors and institutions was more dispersed.The results of keyword analysis showed that how to reduce the adverse reactions of glucocorticoids and special populations was the hotspots of research,with keywords such as"rheumatoid arthritis""damage""belimumab""children""pregnancy".Future research trends would be likely to focus on the assessment of treatment efficacy,prolonged remission,and reduction of disease-related injuries,with emergent keywords such as"validation""prolonged remission""treatment efficacy""renal function"Conclusion The use of glucocorticoids in the treatment of SLE continues to be the focus of the research,but with the increasing concern about adverse reactions,the research focus is gradually moving towards optimizing treatment regimens and exploring novel therapies.Future research needs to focus more on individualized treatment,long-term efficacy assessment and clinical application of emerging therapies.

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