1.Recent Advances of Immune Checkpoint Inhibitors in Treatment of Cervical Cancer
Haojie QIN ; Zhifan ZUO ; Dan CHEN ; Jia LIU ; Shan JIN ; Yang ZHANG ; Yongpeng WANG
Cancer Research on Prevention and Treatment 2025;52(10):848-854
As a hot spot in clinical research today, immune checkpoint inhibitor has been recommended by guidelines in the first- and second-line treatments of advanced cervical cancer as immune monotherapy or combination therapy. It has also achieved good efficacy in clinical practice. In locally advanced cervical cancer, immune checkpoint inhibitors have been included in the guidelines for adjuvant therapy, and good tumor regression effects have been achieved in clinical practice. Based on the results of existing trials, immune checkpoint inhibitors have also shown good clinical potential as neoadjuvant therapy. Furthermore, the issue of immunotherapy rechallenge has increasingly captured clinicians’ attention, offering a potential new therapeutic strategy for cervical cancer patients with prior immunotherapy exposure. In this article, the clinical application and research progress of immune checkpoint inhibitors in the treatment of cervical cancer in recent years are summarized to provide valuable ideas and directions for clinical treatment.
2.Harmonization of 18F-FDG PET brain imaging based on ComBat method: a pilot study
Fangyang JIAO ; Dan WANG ; Yuhua ZHU ; Jiaying LU ; Zizhao JU ; Qian XU ; Jingjie GE ; Tao HUA ; Ping WU ; Kuangyu SHI ; Yihui GUAN ; Chuantao ZUO
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(7):412-416
Objective:To perform harmonization based on the ComBat method for PET brain imaging scanned by different types of scanners from the same manufacturer and explored its effect on center effect.Methods:The three-dimensional (3D) Hoffman brain model was scanned by two different PET/CT instruments (Siemens Biograph64 TruePoint and Biograph128 mCT). Fourteen healthy subjects (8 males, 6 females, age: (57.7±9.5) years) underwent 18F-FDG PET/CT on Siemens Biograph64 TruePoint and 12 healthy subjects (9 males, 3 females, age: (55.8±10.5) years) underwent 18F-FDG PET/CT on Siemens Biograph128 mCT (all from Huashan Hospital, Fudan University; from November 2020 to March 2023). The whole brain was divided into 116 brain regions based on the anatomical automatic labeling (AAL) brain template. The ComBat method was applied to harmonized the PET data from brain model and healthy subjects. Mann-Whitney U test was performed on the radioactive counts and SUV ratios (SUVR) before and after homogenization acquired by both PET/CT instruments. Voxel-based statistical parametric mapping (SPM) independent-sample t test was also performed on data of healthy subjects. Results:In 3D Hoffman brain model, radioactivity counts (5 590.33(4 961.67, 6 102.95) vs 6 116.03(5 420.97, 6 660.66); z=-9.35, P<0.001) and SUVR (1.35(1.19, 1.47) vs 1.37(1.21, 1.49); z=-3.63, P<0.001) were significantly different between the two PET/CT scanners before harmonization and not after harmonization (radioactivity counts: 5 845.95(5 192.68, 6 378.63) vs 5 859.17(5 193.84, 6 380.52); SUVR: 1.35(1.20, 1.48) vs 1.36(1.20, 1.49); both z=-0.68, both P=0.498). In the healthy subjects, radioactive counts in 19 brain regions (12 422.78(11 181.60, 13 424.28)-18 166.40(15 882.80, 18 666.27); z values: from -3.24 to -2.06, all P<0.05) and SUVR in 40 brain regions (1.46(1.41, 1.52)-2.28(2.16, 2.36); z values: from -3.65 to -1.70, all P<0.05) were significantly different between the two scanners before harmonization, while after homogenization there were no statistical differences for all 116 brain regions (radioactivity counts: 9 243.55(8 502.38, 9 854.87)-20 419.60(19 931.51, 21 179.43); z values: from -0.72 to 0, all P>0.05; SUVR: 1.04(1.01, 1.09)-2.32(2.24, 2.40); z values: from -0.82 to 0, all P>0.05). SPM showed that significant differences of glucose metabolism in the cerebral cortex, basal ganglia, midbrain and cerebellum were found in healthy subjects between the two PET/CT scanners before homogenization, and brain regions with obvious differences reduced after homogenization. Conclusion:ComBat harmonization method is efficient at removing the center effect among different types of PET/CT scanners from the same manufacturer and may provide a simple and easy-to-implement homogenization for multicenter brain imaging studies.
3.Establishment of a predictive model for severe acute radiotherapy adverse reactions in nasopharyngeal carcinoma patients based on Olink proteomics
Yaning ZHOU ; Ya LIU ; Dan ZUO ; Junlin YI ; Dan LI ; Ye ZHANG
Cancer Research and Clinic 2024;36(5):321-327
Objective:To investigate the relationship between the inflammatory cytokines level in the plasma of nasopharyngeal carcinoma patients before radiotherapy and acute radiotherapy adverse reactions, and to establish a preliminary model for predicting the risk of severe acute adverse reactions during radiotherapy.Methods:A cross-sectional study was conducted. A total of 85 nasopharyngeal carcinoma patients who received radical radiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from May 2016 to March 2019 were retrospectively collected. The highest grade adverse reactions of radiation oral mucositis, radiation dermatitis and xerostomia during radiotherapy were evaluated according to the American Cancer Radiotherapy Collaboration (RTOG) acute radiation injury evaluation criteria, and the above adverse reactions ≥ grade 3 were treated as the severity. Olink proteomics technology was used to detect the level of 92 inflammatory cytokines (the standardized protein expression values) in the plasma of patients before radiotherapy for the first time. Single factor analysis of variance and independent sample t-test were used to analyze the relationship between inflammatory cytokines and clinical factors, as well as acute adverse reactions during radiotherapy. Based on inflammatory cytokines and/or the clinical factors, binary logistic regression was used to construct a predictive model for the risk of severe acute radiotherapy adverse reactions. Whether the most severe adverse reactions assessed by the American RTOG acute radiation injury evaluation criteria during radiotherapy were severe or not were taken as the gold standard. Receiver operating characteristic (ROC) curve was used to analyze the effectiveness of the established models for judging the severe acute adverse reactions. Results:Among the 85 patients, 68 were males and 17 were females, with the median age [ M ( Q1, Q3)] of 49 years (43 years, 60 years). All patients received radical radiotherapy, of which 64 cases were treated with combination chemotherapy or targeted therapy. A total of 19 cases (22.1%) experienced severe acute radiotherapy adverse reactions. There were statistically significant differences in the levels of interleukin (IL)-22 receptor A1 (IL-22RA1), IL-18 receptor 1(IL-18R1), eotaxin-1 (CCL11), tumor necrosis factor ligand superfamily member 14 (TNFSF14), FMS-like tyrosine kinase 3 ligand (Flt3L), and monocyte chemotactic protein 2 (MCP-2) in the plasma of patients with grade 1, 2, 3 acute radiation oral mucositis before radiotherapy; there were statistically significant differences in the levels of CD244 (all P < 0.05); there were statistically significant differences in the levels of CD244, CC chemokines ligand 20 (CCL20), leukemia inhibitory factor ligand (LIF-R) and IL-4 in the plasma of patients with grade 1, 2, 3 acute radiation dermatitis before radiotherapy (all P < 0.05); there were statistically significant differences in the levels of IL-12B, CXC chemokines ligand 11 (CCL11), LIF-R and IL-33 in the plasma between patients with grade 1 and grade 2 xerostomia before radiotherapy (all P<0.05). The result of single factor analysis of variance showed that the clinical factors were not associated with severe acute radiation adverse reactions (all P > 0.05). Binary logistic regression model M1 was established by selecting 6 clinical factors including age, T staging, N staging, clinical staging, whether to receive chemotherapy or not and whether to suffer from diabetes or not in the literatures. Based on cytokine function and previous literatures, the binary logistic regression model M2 was established by selecting IL-22RA1, IL-18R1, MCP-2, CCL11, CD244, CCL20 and IL-33 from the differential cytokines. A binary logistic regression model M3 was established by combining the above clinical factors with cytokines. The ROC curve analysis showed that the area under the curve of the M1, M2, M3 predictive models for judging the severe acute radiation adverse reactions was 0.781, 0.841, 0.868, respectively. Conclusions:There were differences in the expression levels of various inflammatory cytokines in plasma before radiotherapy among patients with different grades of acute radiotherapy adverse reactions. Building the models based on plasma inflammatory cytokine levels combined with clinical factors before the first radiotherapy could effectively predict the risk of severe acute radiotherapy adverse reactions in patients with nasopharyngeal carcinoma.
4.Connexin 43 hemichannel mediates NLRP3 inflammasome activation and its role in cerebral ischemia
Linhui PENG ; Dan LI ; Zhiqiang HU ; Xialin ZUO
The Journal of Practical Medicine 2024;40(10):1450-1454
Gap junction proteins have a significant impact on the propagation of neuroinflammation after cerebral ischemia.Connexin 43(Cx43),the principal connexin in the central nervous system,typically assembles hexameric hemichannels in an oligomeric state that dock with hemichannels on adjacent cells to form gap junction channels.Ordinarily,the likelihood of cell surface hemichannels opening is minimal.However,during cerebral ischemia,the excessive activation of Cx43 hemichannels leads to the liberation of a substantial quantity of ions(Na+,Cl-,Ca2+,and K+),glutamate,aspartate,and adenosine triphosphate(ATP),thereby resulting in impairment of adjacent cells and aggravation of neuronal injury.Furthermore,the activation of Cx43 hemichannels triggers the release of inflammatory factors,which exhibits a strong association with the activation of NLRP3 inflammasome after cerebral ischemia.Hence,the modulation of Cx43 hemichannels presents a potential avenue for mitigating neuroinflammation and subsequently diminishing cerebral ischemic injury.This article focuses on the relationship between Cx43 hemichannels and NLRP3 inflammasome activation,as well as its role in cerebral ischemia,all of which provide novel insights and therapeutic approaches for managing cerebral ischemia.
5.Status and typing of human papillomavirus infection in male patients in dermatology outpatient department
An-Xin ZUO ; Ying-Chen QIAN ; Xiao-Mei ZHANG ; Dan ZHOU ; Fang TONG ; Wei QIU
Chinese Journal of Infection Control 2024;23(10):1258-1263
Objective To analyze the status and gene subtype distribution of human papillomavirus(HPV)infec-tion in male patients in dermatology outpatient department,provide reference for the prevention and treatment of male HPV infection.Methods Male patients who visited and conducted HPV detection in the dermatology outpa-tient department of a hospital from January 2022 to March 2023 were retrospectively surveyed.Patients were divi-ded into five groups:viral warts group,dermatitis and rash group,urinary tract infection group,balanoposthitis group,and asymptomatic group.Relationship between genotype distribution and patient age,clinical diagnosis,and symptom types was statistically analyzed.Results A total of 1 035 male patients underwent HPV detection,out of which 567 were positive,with a positive detection rate of 54.78%.286,164,6,109,and 470 cases were from viral warts,dermatitis and rash,urinary tract infection,balanoposthitis,and asymptomatic group,respectively.21 sub-types of HPV were detected,with the top three subtypes being type 6(17.97%),11(12.37%),and 52(8.70%).The positive rate of single type HPV infection was 29.86%,accounting for 54.50%.Positive rates of infection,low-risk infection,and multiple mixed infection in different age groups were compared,differences were all statisti-cally significant(all P<0.05).The positive infection rate in the age group of<20 years old was higher than that in the age groups of 20-<30,30-<40,and 40-<50 years old,differences were all statistically significant(all P<0.05).Among the positive patients,199 cases(35.10%)had no clinical symptoms,while 368(64.90%)had clinical symptoms,mainly manifested as viral warts(40.74%,n=231).In viral warts group,HPV-positive pa-tients were mainly of low-risk type,accounting for 80.95%;In balanoposthitis group,HPV-positive patients were mainly of high-risk type,accounting for 84.78%;In asymptomatic group,HPV-positive patients were mainly infected with high-risk types,accounting for 86.43%.Conclusion HPV infection in male outpatient department of derma-tology is mainly single type infection.The clinical diagnosis of low-risk infection is mainly viral warts,while high-risk in-fection is mainly manifested as balanoposthitis.In asymptomatic group,positive infections are mainly of high-risk type.
6.Safety and efficacy of ultrasound-guided negative pressure suction and minimally invasive rotatory excision technique in the treatment of complex encapsulated lesions
Yi HUANG ; Xin ZHANG ; Lian XUE ; Chuyun ZHENG ; Min ZHAO ; Nan ZHAO ; Zhongqin HE ; Dan SU ; Lei ZUO
Chinese Journal of Ultrasonography 2024;33(5):434-440
Objective:To evaluate the safety and efficacy of ultrasound-guided percutaneous negative pressure suction and minimally invasive rotatory excision technique for the treatment of complex encapsulated lesions.Methods:A total of 48 patients(48 lesions) with complex encapsulated lesions who underwent ultrasound-guided percutaneous negative pressure suction and minimally invasive rotatory excision technique at Xi′an Chest Hospital from January to October 2023 were retrospectively enrolled, including 39 cases of encapsulated abscess, 7 cases of encapsulated effusion, and 2 cases of encapsulated haematoma; the distribution of the bacterial flora of the abscesses were as follows: 24 cases of tuberculous abscess, 14 cases of bacterial abscess, 1 case of bacterial combined bacterial-fungal abscess, and 7 cases of encapsulated effusion were tuberculous pleurisy, and the clinical data were analysed retrospectively. The maximum upper and lower diameters, right and left diameters, and anterior and posterior diameters of the lesions were measured by ultrasound before and after the operation. The patients′ various biochemical indicators (C-reactive protein, white blood cell count, neutrophil count, erythrocyte sedimentation rate) were detected. The intraoperative and postoperative complications, postoperative outcomes, and postoperative clinical symptoms were recorded.Results:Of the 48 patients, 39 were cured and discharged after negative pressure suction and rotatory excision technique, and 9 patients were cured and discharged after surgical incision and drainage of the lesions. The overall effective rate of negative pressure suction and rotatory excision treatment reached 81.25%, and the average number of days of tube placement was (11.81±7.22) days, and the average number of days of follow-up was (35.77±19.39) days. Compared with preoperative values, the upper and lower diameters, the left and right diameters, and the anterior and posterior diameters of the lesions were all reduced after operation [5.80 (4.95, 7.95)cm vs 8.00 (6.00, 11.82)cm, 4.00 (3.25, 5.00)cm vs 5.85 (4.52, 7.65)cm, 1.80 (1.00, 2.90)cm vs 3.40 (2.50, 6.15)cm, all P<0.01]; and postoperative C-reactive protein, white blood cell count and neutrophil count all decreased (all P<0.05). Before operation there were 31 cases of local swelling, 16 cases of pain, 12 cases of activity limitation, 12 cases of fever, 7 cases of chest tightness, and 6 cases of shortness of breath, and during postoperative follow-up, there were 4 cases of local swelling, 5 cases of pain, and 4 cases of activity limitation. The symptoms of fever, chest tightness, and shortness of breath all disappeared, and there was a statistically significant difference between preoperation and postoperation (all P<0.05). There were no adverse events or complications associated with the intraoperative and postoperative follow-up of negative pressure suction and rotatory excision treatment. Conclusions:Ultrasound-guided percutaneous negative pressure suction and invasive rotatory excision technique for the treatment of complex encapsulated lesions can significantly reduce lesion size, reduce inflammatory response and improve patient symptoms, which is a safe, effective and minimally invasive technique.
7.Research progress in late toxicity of oropharyngeal cancer after radical intensity-modulated radiotherapy
Ya LIU ; Yaning ZHOU ; Dan ZUO ; Junlin YI ; Ye ZHANG
Chinese Journal of Radiation Oncology 2024;33(5):461-465
Intensity-modulated radiotherapy (IMRT) is a radical treatment for oropharyngeal carcinoma. The 5-year overall survival (OS) is approximately 60%, and 80% for human papillomavirus (HPV)-related oropharyngeal carcinoma patients. Late toxicities after IMRT, including xerostomia, dysphagia, hypothyroidism, trismus, osteoradionecrosis and caries, and lower cranial neuropathy, seriously affect the quality of life of long-term survivors. The research on treatment de-intensification for HPV-related oropharyngeal cancer has been widely carried out at home and abroad, but there is little research focusing on late toxicity. In this article, related research progress in the incidence, treatment, prediction of late toxicity after IMRT was reviewed, aiming to provide reference for research on radiation-induced injury in de-intensification therapy research, thereby further optimizing comprehensive treatment strategies.
8. Effect Xuefu Zhuyu decoction on endothelial-to-mesenchymal transition of pulmonary artery endothelial cells and its mechanism
Zuo-Mei ZENG ; Xin-Yue WANG ; Lei-Yu TIAN ; Li-Dan CUI ; Jian GUO ; Yu-Cai CHEN
Chinese Pharmacological Bulletin 2024;40(1):155-161
Aim To investigate the effect of Xuefu Zhuyu decoction on transforming growth factor-β1(TGF-β1 ) -induced endothelial-to-mesenchymal transition (EndMT) of pulmonary microvascular endothelial cells ( PMVEC), and further analyze the mechanism related to the TGF-β1/Smad signaling pathway. Method To construct an EndMT cell model, PMVEC was treated with TGF-β1 (5 μg · L
9.Relationship between parenting style and emotional behavior problems in children with development dyslexia
YIN Feifei, ZHANG Jing, ZHONG Lin, LI Dan, XIAO Xinyu, ZUO Pengxiang
Chinese Journal of School Health 2024;45(7):988-992
Objective:
To explore the relationship between parenting style and emotional behavior problems in children with development dyslexia (DD), so as to provide reference for family support and intervention measures.
Methods:
From June to September 2023, 201 children in DD group and typically developing matched by age and sex were selected from the students in grades 3-6 of 4 primary schools in a district of Xinjiang by random cluster sampling method. The Childrens Version of the Parenting Style Scale and the Strength and Difficulty Scale were administered, and the occurrence of childrens emotional behavior problems and parentingstyles in the two groups were compared by Chisquare test and Wicoxon rank sum test. The correlation between parents parenting styles and childrens emotional behavior problems was analyzed by generalized linear regression.
Results:
The detection rates of emotional behavior problems were 45.77% in DD group and 15.42% in normal control children group. The differences in parenting styles between fathers and mothers of the DD group and the normal control group were statistically significant in terms of emotional warmth, parenting anxiety, and overprotection (Z=4.02, 29.03; 4.94, 26.32; 23.47, 5.30, P<0.05). Generalized linear regression analysis showed that father affective warmth was positively correlated with emotional symptoms, hyperactivity, peer interaction problems and prosocial behaviors (β=0.08, 0.05, 0.05, 0.09, P<0.05). The emotional warmth of mothers in DD group was negatively correlated with emotional symptoms, conduct problems, hyperactivity and peer interaction problems (β=-0.18, -0.08, -0.07, -0.08, P<0.05).
Conclusions
Parenting style is an important factor affecting the emotional behavior problems of DD children. Improving parenting style can reduce the occurrence of emotional behavior problems of DD children.
10.Relationship between executive function and social adjustment in children with developmental dyslexia
YIN Feifei, XIAO Xinyu, ZHANG Han, ZUO Pengxiang,LI Dan
Chinese Journal of School Health 2024;45(6):835-839
Objective:
To explore the characteristics of executive function of developmental dyslexic children and the relationship with social adaptability, in order to provide a scientific basis for promoting healthy development of developmental dyslexic children.
Methods:
From June to September 2023, 85 students in the developmental dyslexia group, 85 students in the biological agematched group and 85 students in the reading levelmatched group were selected from the third to sixth grades of two elementary school in a region of Xinjiang by cluster random sampling method. Their executive function was assessed by the Stroop procedure, the 2-back procedure and the numerical conversion procedure, respectively, and their social adaptive ability was assessed by the Social Adaptation Scale for Children and Adolescents. An analysis of variance (ANOVA) was used to compare the differences in executive function and social adjustment among the three groups, and Pearsons correlation was used to analyze the relationship between executive function and social adjustment in developmental dyslexic children.
Results:
Children in the developmental dyslexia group had lower correctness on the Stroop colorword task (0.72±0.21), the 2-back task (0.32±0.13), the digitswitching task (0.54±0.16) and the total score of social adjustment (165.39±31.36) than children in the biological agematched (0.80±0.19,0.38±0.11,0.61±0.15,181.71±31.85) and reading levelmatched group (0.79±0.17,0.35±0.07,0.58±0.15,175.71±27.48) (F=4.54,5.05,4.97,6.31,P<0.01). The inhibition (Stroop colorword task correct rate) and conversion subcomponent (digitswitching task correct rate) of the executive function of children in the developmental dyslexia group were both positively correlated with their social adaptive ability (r=0.34,0.43), and the refreshing subcomponent of the executive function (2-back task correct rate) was negatively correlated with their social adaptive ability (r=-0.27) (P<0.05).
Conclusions
Children with developmental dyslexia have executive function deficits and social maladjustment, and their executive function is related to social adjustment. Measures should be taken to improve the executive function of developmental dyslexic children and to improve their social adaptation.


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