1.Literature analysis of tislelizumab-induced Stevens-Johnson syndrome and toxic epidermal necrolysis
Rui HAN ; Mingxi SHEN ; Hua YANG ; Zhaoshuai JI
China Pharmacy 2025;36(16):2046-2050
OBJECTIVE To analyze the clinical characteristics of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) induced by tislelizumab, providing evidence for clinical medication safety. METHODS Case reports of tislelizumab-related SJS/TEN were retrieved from CNKI, VIP, Wanfang Data, PubMed, ScienceDirect, and Embase. Descriptive analysis was performed. RESULTS Seventeen cases from 17 publications were included (SJS 4 cases, TEN 13 cases). Among them, there were 10 males and 7 females. Twelve patients were aged between 70 and 79 years. The predominant tumor type was lung cancer (10 cases). Thirteen patients received combination therapy with chemotherapeutic drugs. The median onset time of SJS/ TEN was 26 (4, 104) days. Nine patients developed SJS/TEN after the first administration of the drug. Sixteen patients exhibited prodromal rash symptoms, primarily characterized by severe skin damage such as skin detachment, accompanied by mucosal injury. Sixteen patients improved after symptomatic treatment, while one patient died. CONCLUSIONS Tislelizumab-associated SJS/TEN risk is higher in elderly patients, males, those with lung cancer and those receiving combination chemotherapy. Mucosal lesions and atypical rashes may indicate the early onset of SJS/TEN. During clinical use, pharmaceutical care can be carried out through measures such as identifying high-risk populations, closely monitoring skin symptoms from the first administration to the fifth treatment cycle, and enhancing patient education. When relevant symptoms occur, the medication should be promptly discontinued and symptomatic treatment should be administered to ensure the patient’s medication safety.
2.Therapeutic effect of oral Xuefu Zhuyu Pill combined with intravitreal injection of Aflibercept in the treatment of retinal vein occlusion
Ran SHEN ; Hongying JI ; Hongyu CUI ; Lequan YANG ; Lixia GUO
International Eye Science 2025;25(9):1532-1536
AIM: To explore the therapeutic effect of oral Xuefu Zhuyu Pill combined with intravitreal injection of aflibercept in the treatment of retinal vein occlusion(RVO).METHODS: A total of 80 patients(80 eyes)with RVO admitted to our hospital from January 2021 to March 2024 were prospectively selected. According to the treatment method, they were divided into a control group of 40 patients treated with intravitreal injection of aflibercept, and an observation group of 40 patients treated with oral Xuefu Zhuyu Pill combined with intravitreal injection of aflibercept. The efficacy, TCM syndrome score, retinal microcirculation parameters, macular edema(ME), and adverse reactions were compared between the two groups of patients in the treatment of RVO.RESULTS: All patients have completed follow-up. The clinical effective rate of the observation group after treatment was 95%, obviously higher than that of the control group(80%; χ2=4.114, P=0.043). After treatment for 3 mo, the traditional Chinese medicine syndrome scores, foveal avascular area(FAZ)area, FAZ circumference, macular central retinal thickness, and neovascularization leakage area of both groups decreased, the overall blood flow density of the superficial capillary plexus(SCP)and deep capillary plexuses(DCP)increased, and the observation group showed better results than the control group(all P<0.05). There was no statistically significant difference in the occurrence of adverse reactions between the two groups during the treatment period(P>0.05).CONCLUSION: Oral administration of Xuefu Zhuyu Pill combined with intravitreal injection of aflibercept in the treatment of RVO can improve retinal microcirculation, enhance vision, restore ocular blood circulation, improve bleeding, promote ME absorption, and improve clinical efficacy.
3.Precision therapy targeting CAMK2 to overcome resistance to EGFR inhibitors in FAT1 -mutated oral squamous cell carcinoma.
Yumeng LIN ; Yibo HUANG ; Bowen YANG ; You ZHANG ; Ning JI ; Jing LI ; Yu ZHOU ; Ying-Qiang SHEN ; Qianming CHEN
Chinese Medical Journal 2025;138(15):1853-1865
BACKGROUND:
Oral squamous cell carcinoma (OSCC) is a prevalent type of cancer with a high mortality rate in its late stages. One of the major challenges in OSCC treatment is the resistance to epidermal growth factor receptor (EGFR) inhibitors. Therefore, it is imperative to elucidate the mechanism underlying drug resistance and develop appropriate precision therapy strategies to enhance clinical efficacy.
METHODS:
To evaluate the efficacy of the combination of the Ca 2+ /calmodulin-dependent protein kinase II (CAMK2) inhibitor KN93 and EGFR inhibitors, we performed in vitro and in vivo experiments using two FAT atypical cadherin 1 ( FAT1 )-deficient (SCC9 and SCC25) and two FAT1 wild-type (SCC47 and HN12) OSCC cell lines. We assessed the effects of EGFR inhibitors (afatinib or cetuximab), KN93, or their combination on the malignant phenotype of OSCC in vivo and in vitro . The alterations in protein expression levels of members of the EGFR signaling pathway and SRY-box transcription factor 2 (SOX2) were analyzed. Changes in the yes-associated protein 1 (YAP1) protein were characterized. Moreover, we analyzed mitochondrial dysfunction. Besides, the effects of combination therapy on mitochondrial dynamics were also evaluated.
RESULTS:
OSCC with FAT1 mutations exhibited resistance to EGFR inhibitors treatment. The combination of KN93 and EGFR inhibitors significantly inhibited the proliferation, survival, and migration of FAT1 -mutated OSCC cells and suppressed tumor growth in vivo . Mechanistically, combination therapy enhanced the therapeutic sensitivity of FAT1 -mutated OSCC cells to EGFR inhibitors by modulating the EGFR pathway and downregulated tumor stemness-related proteins. Furthermore, combination therapy induced reactive oxygen species (ROS)-mediated mitochondrial dysfunction and disrupted mitochondrial dynamics, ultimately resulting in tumor suppression.
CONCLUSION
Combination therapy with EGFR inhibitors and KN93 could be a novel precision therapeutic strategy and a potential clinical solution for EGFR-resistant OSCC patients with FAT1 mutations.
Humans
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ErbB Receptors/metabolism*
;
Mouth Neoplasms/metabolism*
;
Cell Line, Tumor
;
Animals
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Drug Resistance, Neoplasm/genetics*
;
Cadherins/metabolism*
;
Carcinoma, Squamous Cell/metabolism*
;
Mice
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Mutation/genetics*
;
Mice, Nude
;
Protein Kinase Inhibitors/therapeutic use*
;
Cetuximab/pharmacology*
;
Afatinib/therapeutic use*
;
Cell Proliferation/drug effects*
;
Signal Transduction/drug effects*
4.Association between Fish Consumption and Stroke Incidence Across Different Predicted Risk Populations: A Prospective Cohort Study from China.
Hong Yue HU ; Fang Chao LIU ; Ke Yong HUANG ; Chong SHEN ; Jian LIAO ; Jian Xin LI ; Chen Xi YUAN ; Ying LI ; Xue Li YANG ; Ji Chun CHEN ; Jie CAO ; Shu Feng CHEN ; Dong Sheng HU ; Jian Feng HUANG ; Xiang Feng LU ; Dong Feng GU
Biomedical and Environmental Sciences 2025;38(1):15-26
OBJECTIVE:
The relationship between fish consumption and stroke is inconsistent, and it is uncertain whether this association varies across predicted stroke risks.
METHODS:
A cohort study comprising 95,800 participants from the Prediction for Atherosclerotic Cardiovascular Disease Risk in China project was conducted. A standardized questionnaire was used to collect data on fish consumption. Participants were stratified into low- and moderate-to-high-risk categories based on their 10-year stroke risk prediction scores. Hazard ratios ( HRs) and 95% confidence intervals ( CIs) were estimated using Cox proportional hazard models and additive interaction by relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (SI).
RESULTS:
During 703,869 person-years of follow-up, 2,773 incident stroke events were identified. Higher fish consumption was associated with a lower risk of stroke, particularly among moderate-to-high-risk individuals ( HR = 0.53, 95% CI: 0.47-0.60) than among low-risk individuals ( HR = 0.64, 95% CI: 0.49-0.85). A significant additive interaction between fish consumption and predicted stroke risk was observed (RERI = 4.08, 95% CI: 2.80-5.36; SI = 1.64, 95% CI: 1.42-1.89; AP = 0.36, 95% CI: 0.28-0.43).
CONCLUSION
Higher fish consumption was associated with a lower risk of stroke, and this beneficial association was more pronounced in individuals with moderate-to-high stroke risk.
Humans
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China/epidemiology*
;
Male
;
Female
;
Stroke/etiology*
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Middle Aged
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Prospective Studies
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Incidence
;
Aged
;
Animals
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Fishes
;
Risk Factors
;
Diet
;
Seafood
;
Adult
;
Cohort Studies
5.Independent and Interactive Effects of Air Pollutants, Meteorological Factors, and Green Space on Tuberculosis Incidence in Shanghai.
Qi YE ; Jing CHEN ; Ya Ting JI ; Xiao Yu LU ; Jia le DENG ; Nan LI ; Wei WEI ; Ren Jie HOU ; Zhi Yuan LI ; Jian Bang XIANG ; Xu GAO ; Xin SHEN ; Chong Guang YANG
Biomedical and Environmental Sciences 2025;38(7):792-809
OBJECTIVE:
To assess the independent and combined effects of air pollutants, meteorological factors, and greenspace exposure on new tuberculosis (TB) cases.
METHODS:
TB case data from Shanghai (2013-2018) were obtained from the Shanghai Center for Disease Control and Prevention. Environmental data on air pollutants, meteorological variables, and greenspace exposure were obtained from the National Tibetan Plateau Data Center. We employed a distributed-lag nonlinear model to assess the effects of these environmental factors on TB cases.
RESULTS:
Increased TB risk was linked to PM 2.5, PM 10, and rainfall, whereas NO 2, SO 2, and air pressure were associated with a reduced risk. Specifically, the strongest cumulative effects occurred at various lags: PM 2.5 ( RR = 1.166, 95% CI: 1.026-1.325) at 0-19 weeks; PM 10 ( RR = 1.167, 95% CI: 1.028-1.324) at 0-18 weeks; NO 2 ( RR = 0.968, 95% CI: 0.938-0.999) at 0-1 weeks; SO 2 ( RR = 0.945, 95% CI: 0.894-0.999) at 0-2 weeks; air pressure ( RR = 0.604, 95% CI: 0.447-0.816) at 0-8 weeks; and rainfall ( RR = 1.404, 95% CI: 1.076-1.833) at 0-22 weeks. Green space exposure did not significantly impact TB cases. Additionally, low temperatures amplified the effect of PM 2.5 on TB.
CONCLUSION
Exposure to PM 2.5, PM 10, and rainfall increased the risk of TB, highlighting the need to address air pollutants for the prevention of TB in Shanghai.
China/epidemiology*
;
Humans
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Air Pollutants/analysis*
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Tuberculosis/epidemiology*
;
Incidence
;
Meteorological Concepts
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Particulate Matter/adverse effects*
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Environmental Exposure
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Male
;
Female
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Adult
;
Air Pollution
;
Middle Aged
6.Adverse drug reactions in patients treated with sodium dimercaptosulphonate injection for mercury poisoning and influencing factors
Ye CHEN ; Huixia JI ; Dandan LIU ; Yang SHEN
Journal of Environmental and Occupational Medicine 2024;41(9):1020-1024
Background Adverse drug reactions (ADRs) to sodium dimercaptosulphonate (DMPS) mercury removal treatment have been reported in occupational mercury poisoning. In recent years, the number of cases of mercury poisoning due to mercury-containing cosmetics has been increasing, and ADRs to the use of DMPS are common in clinical practice. Objective To investigate the occurrence of ADRs and the influencing factors in patients with chronic mercury poisoning and mercury exposure treated with DMPS for mercury removal. Methods Patients treated with DMPS due to mercury poisoning at the Occupational Disease Department of Nanjing Prevention and Treatment Center for Occupational Diseases from June 2017 to December 2023 were included in the study. Information on demographics, baseline characteristics, and treatment regimens was collected at admission. Information on secondhand smoke, place of residence, and blood groups not collected at admission was collected in follow-up. The patients were divided into two groups according to whether ADRs occurred after the use of DMPS and were compared for clinical characteristics, and the influencing factors related to the occurrence of ADRs after DMPS treatment were analyzed by binary logistic regression. Results A total of 72 patients were enrolled in the study, of which 26 reported ADRs during mercury removal. A total of 29 ADRs occurred, mainly rash in 11 cases (37.9%), fever in 5 cases (17.2%), and nausea in 4 cases (13.8%). Most ADRs occurred in the second course (7 cases, 26.9%) and the third course (9 cases, 34.6%). Of the 22 non-menopausal women who experienced ADRs, 13 (59.1%) used DMPS in the week prior to menstruation. The logistic regression analysis showed that smoking (OR=27.911, 95%CI: 2.835, 725.809) and blood type O (OR=6.885, 95%CI: 2.014, 26.896) were associated with elevated occurrence of ADRs after DMPS treatment. Conclusions The probability of ADRs after DMPS treatment is not low, but mild presentations are predominant and resolved with immediate treatment, with a favourable prognosis. The O blood group, smoking individuals, and female patients using DMPS one week before menstruation may be more prone to ADRs.
7.Association between air pollutants and pediatric outpatient volumes in Baoshan District
YUAN Zhen ; SHEN Xianbiao ; JI Peng ; YAN Lili ; YANG Cheng
Journal of Preventive Medicine 2024;36(2):143-146
Objective:
To explore the relationship between air pollutants and pediatric outpatient volumes in Baoshan District, Shanghai Municipality.
Methods:
Data of meteorological factors, air pollutants and pediatric outpatient volumes in four general hospitals were collected in Baoshan District from 2015 to 2019, and a generalized additive model was used to fit the Poisson-like distribution. The exposure-response relationship between fine particulate matter (PM2.5), sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3) and total pediatric outpatient volumes and pediatric respiratory outpatients.
Results:
The median of the average daily temperature and relative humidity were 18.7 (interquartile range, 14.4) ℃ and 74.5% (interquartile range, 18.0%) in Baoshan District from 2015 to 2019, respectively. The median of the average daily concentrations of PM2.5, SO2, NO2 and O3 were 35.0 (interquartile range, 35.0), 11.0 (interquartile range, 7.0), 45.0 (interquartile range, 31.8) and 84.5 (interquartile range, 50.0) μg/m3, respectively. The median of the average daily total and respiratory pediatric outpatient volumes were 680 (interquartile range, 246) and 392 (interquartile range, 253). Spearman rank correlation analysis showed that temperature, relative humidity, PM2.5, SO2, NO2 and O3 were associated with total and respiratory pediatric outpatient volume (all P<0.05). Under the single pollutant model, the excess risk of total and respiratory pediatric outpatient volume due to PM2.5 (ER=0.318, 0.257), SO2 (ER=1.610, 2.546), and NO2 (ER=0.808, 0.839) reached the maximum effect on the same day, and the effect of O3 (ER=0.102, 0.222) reached its maximum at the first day of lag. Under the multi-pollutant model, after O3, SO2, NO2 and PM2.5 were introduced, a exposure-response relationship between air pollutants and total pediatric outpatient volumes was the largest on the sixth day after the lag (ER=0.419). There was no exposure-response relationship between air pollutants and respiratory pediatric outpatient volumes.
Conclusion
PM2.5, SO2, NO2 and O3 are associated with total and respiratory pediatric outpatient volumes, and the lag effects due to different air pollutants are different.
8.A novel TNKS/USP25 inhibitor blocks the Wnt pathway to overcome multi-drug resistance in TNKS-overexpressing colorectal cancer.
Hongrui ZHU ; Yamin GAO ; Liyun LIU ; Mengyu TAO ; Xiao LIN ; Yijia CHENG ; Yaoyao SHEN ; Haitao XUE ; Li GUAN ; Huimin ZHAO ; Li LIU ; Shuping WANG ; Fan YANG ; Yongjun ZHOU ; Hongze LIAO ; Fan SUN ; Houwen LIN
Acta Pharmaceutica Sinica B 2024;14(1):207-222
Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APCmin/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.
9.Summary of the best evidence of accelerated rehabilitation nursing in perioperative period of patients undergoing hip and knee arthroplasty
Huiling WANG ; Hui LI ; Bing SHAO ; Ning HAN ; Yang SHEN ; Xianan SONG ; Zhengang JI
Chinese Journal of Practical Nursing 2024;40(2):110-117
Objective:To search, evaluate and summarize the best evidence summary of perioperative accelerated rehabilitation nursing for patients undergoing hip and knee arthroplasty, so as to provide reference for clinical perioperative nursing.Methods:Evidence-based nursing methods were used to search for relevant databases such as BMJ Best Practice, UpToDate, PubMed, CINAHL, and CNKI, etc.. The search period was from December 2010 to December 2022. Four researchers independently evaluated the quality of the guidelines, and two researchers independently evaluated the quality of expert consensus and system evaluation. Finally, the included literature was summarized.Results:A total of 12 pieces of literature, 3 guidelines, 5 expert consensus and 4 systematic reviews were included. From 13 aspects of preoperative education, preoperative optimization, anesthesia management, perioperative blood management, perioperative pain management, perioperative fluid management, perioperative temperature protection, infection prevention, thrombus prevention, postoperative nausea and vomiting, postoperative drainage, functional exercise, and perioperative rehabilitation promotion, 35 pieces of the best evidence for hip and knee replacement patients to accelerate rehabilitation nursing in the perioperative period was summarized.Conclusions:This study summarizes the best evidence of accelerated rehabilitation nursing in the perioperative period of hip and knee arthroplasty, aiming to build and standardize the accelerated rehabilitation nursing scheme in the perioperative period of hip and knee arthroplasty, so as to provide reference for clinical perioperative nursing.
10.The Effect and Mechanism of Estrogen and Estrogen Receptors in the Pathogenesis of Non-Invasive Fungal Rhinosinusitis
Chuanmei YANG ; Yafei SU ; Luhua SHEN ; Hong ZHANG ; Teng WANG ; Siyu JI ; Zhiyong XIAO
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(6):1017-1025
[Objective]To explore the role of estrogen and estrogen receptor (ER) in the pathogenesis and regulation of non-invasive fungal rhinosinusitis (NIFR).[Methods]Totally 60 patients with NIFS who met the inclusion criteria in Fuzhou Second General Hospital from November 2020 to November 2023 were selected as the NIFS group,while 30 healthy volunteers were recruited as the blank control group. Samples of each group were collected. The number of eosinophils and mast cells in each group were detected by HE staining;ER expression was detected by immunohistochemistry and immunofluorescence;mRNA expression levels of NF-κB,IKK and MASPIN were detected by qPCR;and protein expression levels of NF-κB,IKK and MASPIN were detected by immunohistochemistry and Western blot.[Results]In the NIFS group,the counts of eosinophils and mast cells were significantly increased respectively,compared with those in the control group,and the inter-group differences are statistically significant (P<0.01 and P<0.05,respectively). The Estrogen Receptor (ER) score in the NIFS group was significantly increased compared with that in the control group,and the inter-group differences are statistically significant (P<0.05). Additionally,the average high-density value in the NIFS group was significantly increased compared with that in the control group,and the inter-group differences are statistically significant (P<0.01). The expression levels of NF-κB,IKK,and MASPIN in the NIFS group were significantly increased respectively,compared with those in the control group,and the inter-group differences are statistically significant (P<0.01,P<0.05,and P<0.01,respectively). The mRNA expression levels of NF-κB,IKK,and MASPIN in the NIFS group were significantly increased,respectively,compared with those in the control group (P<0.01). Furthermore,the protein expression levels of NF-κB,IKK,and MASPIN in the NIFS group were increased,respectively,and the inter-group differences are statistically significant (P<0.01,P<0.01,and P<0.05,respectively).[Conclusion]Our results show that the significant increase in the number of eosinophils and mast cells,and in the expression levels of ER,NF-κB,IKK and MASPIN may indicate a significant increase in eosinophil and mast cell infiltration in ER positive patients,and suggest the involvement of estrogen and its receptors in the pathogenesis of NIFS.


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