1.Effect of pegylated interferon-α-2b therapy on cytotoxicity of virus-specific CD8+ T cells in HBeAg-negative patients with chronic hepatitis B virus infection
Lei QIN ; Guangpeng LI ; Peijun SHEN ; Lanfang ZHANG ; Xiaofei YANG ; Meijuan PENG ; Ye ZHANG
Journal of Clinical Hepatology 2025;41(4):628-636
ObjectiveTo investigate the change in the activity of hepatitis B virus (HBV)-specific CD8+ T cells after pegylated interferon-α-2b (PEG-IFN-α-2b) therapy in HBeAg-negative patients with chronic HBV infection. MethodsA total of 53 HBeAg-negative patients with chronic HBV infection who attended The First Affiliated Hospital of Xinxiang Medical University and Tangdu Hospital of Air Force Mdical University from April 2020 to June 2022 were enrolled and treated with PEG-IFN-α-2b (180 μg/week, subcutaneous injection) antiviral therapy. The study endpoint was HBsAg clearance (course of treatment<48 weeks) or 48 weeks (course of treatment≥48 weeks). Peripheral blood mononuclear cells were isolated at baseline and study endpoint, and peripheral blood T cell counts were measured. Enzyme-linked immunospot assay was used to measure the frequency of HBV-specific CD8+ T cells secreting perforin, granzyme B, and interferon-γ. A total of 17 HLA-A*02-restricted patients were selected, and CD8+ T cells were purified to establish direct- and indirect-contact co-culture systems for HBV-specific CD8+ T cells and HepG2.2.15 cells. The level of lactate dehydrogenase in supernatant was measured to calculate the mortality rate of HepG2.2.15 cells, and the levels of HBV DNA, cytotoxic molecules, and cytokines in supernatant were also measured. Flow cytometry was used to measure the expression of apoptosis ligands, and the cytotoxicity of HBV-specific CD8+ T cells was evaluated. The independent samples t-test or the paired t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test or the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups. ResultsThe HBsAg clearance rate at study endpoint was 30.19% (16/53). There were no significant differences in peripheral blood T cell counts (CD3+, CD4+, and CD8+ T cells) between baseline and study endpoint (P>0.05). At study endpoint, there was a significant increase in the frequency of HBV-specific CD8+ T cells secreting perforin, granzyme B, and interferon-γ (U=177.50, t=11.90, U=186.50, all P<0.001), and the patients with HBsAg clearance had a significantly higher frequency of such HBV-specific CD8+ T cells than those without HBsAg clearance (U=120.50, t=2.73, U=121.50, all P<0.01). In the direct- and indirect-contact co-culture systems at study endpoint, HBV-specific CD8+ T cells induced a significant reduction in HBV DNA in the supernatant of HepG2.2.15 cells (all P<0.001) and significant increases in the secretion of interferon-γ and tumor necrosis factor-α (all P<0.05); in the direct-contact co-culture system, HBV-specific CD8+ T cells induced significant increases in the mortality rate of HepG2.2.15 cells (13.62%±3.27% vs 11.39%±2.40%, t=2.27, P=0.030) and the secretion of perforin and granzyme B (t=72.50, U=52.50, both P<0.05). In the direct- and indirect-contact co-culture systems, compared with HBV-specific CD8+ T cells from the patients without HBsAg clearance, the HBV-specific CD8+ T cells from patients with HBsAg clearance had a significantly greater reduction in HBV DNA (P<0.05) and significant increases in the secretion of interferon-γ and tumor necrosis factor-α (P<0.05). ConclusionPEG-IFN-α-2b therapy can help to achieve a relatively high HBsAg clearance rate in HBeAg-negative patients with chronic HBV infection, and the activity of HBV-specific CD8+ T cells is significantly enhanced, which is closely associated with HBsAg clearance.
2.Factors influencing cardiopulmonary resuscitation competency among community medical staff in Beijing and countermeasures
Bin WANG ; Qingbian MA ; Kang ZHENG ; Lanfang DU ; Hua ZHANG
Chinese Journal of Medical Education Research 2024;23(2):200-205
Objective:To investigate the status of the knowledge of cardiopulmonary resuscitation (CPR) in community medical staff, and analyze the factors influencing their levels of CPR knowledge and skills, and to provide a basis for improving community CPR training programs.Methods:From January to March 2022, we conducted a survey for the knowledge of CPR among community medical staff in Beijing through WeChat using a self-made questionnaire based on the 2016 National Consensus on Cardiopulmonary Resuscitation in China and the 2020 American Heart Association CPR guidelines. The questionnaire mainly focused on the basic information and CPR knowledge (full score, 17 points) and practice of medical workers. R4.0.3 software was used to perform multiple linear regression analysis.Results:A total of 990 medical personnel from 51 communities effectively responded to the survey. The mean CPR knowledge score was (10.27±2.87) points. The regression analysis showed that the CPR score was significantly lower in groups of male, non-31-40-year-olds, technical degrees, only 0-1 trainings in two years, not ever practicing CPR, and not ever using an automated external defibrillator (AED), suggesting that sex, age, educational attainment, training frequency, whether having the experience of CPR and AED practice or not were independent factors influencing the CPR score of community medical staff.Conclusions:The CPR competency of community medical staff needs to be improved, especially for those with technical degrees and non-31-40-year-olds. The training frequency should be increased based on the Ebbinghaus' forgetting curve, and stratified training is recommended for different populations. Those without practical experience should receive more CPR training with real-time feedback devices and high-fidelity simulation to improve their CPR skills.
3.Analysis of drug resistance and virulence genes of clinical isolates of Staphylococcus aureus in Northwest Hubei Province
Yating ZHANG ; Wuhui JIANG ; Kang YANG ; Lanfang LIU ; Yan YANG
International Journal of Laboratory Medicine 2024;45(19):2311-2315,2322
Objective To investigate the drug resistance and virulence genes of Staphylococcus aureus iso-lated from clinical specimens of hospitals in northwest Hubei province.Methods A total of 142 clinical iso-lates of Staphylococcus aureus were collected from 5 hospitals in Shiyan City from 2019 to 2021.Broth mi-crodilution method was used to detect drug resistance,and PCR method was used to detect 9 enterotoxin genes such as sea,mecA and Panton-Valentine leukocidein(PVL)virulence genes.Results A total of 44 methicillin-resistant Staphylococcus aureus(MRSA)strains were detected in 142 strains of Staphylococcus aureus,and the detection rate was 30.99%(44/142).The resistance rates of MRSA to erythromycin,clindamycin,levo-floxacin,tetracycline and gentamicin were higher than those of methicillin-sensitive Staphylococcus aureus(MSSA),and the differences were statistically significant(P<0.05).The detection rate of enterotoxin genes was 70.42%(100/142),among which the detection rates of classic enterotoxin genes(sea-see)and new ente-rotoxin genes(seg-sej)were 47.18%(67/142)and 42.25%(60/142),respectively.The detection rate of PVL virulence genes was 13.38%(19/142),among which the detection rates of MSSA and MRSA were 9.18%(9/98)and 22.73%(10/44),respectively,and the difference was statistically significant(P<0.05).Conclusion The detection rate of enterotoxin and PVL gene of Staphylococcus aureus isolated from clinical isolates is high.In clinical di-agnosis and treatment,it is necessary to control hospital infection,take effective isolation measures in time and strengthen the monitoring of PVL gene.
4.The regulatory effect of interleukin-33 signaling pathway on monocytes in patients with hepatitis B virus-associated hepatocellular carcinoma
Lu YANG ; Lanfang ZHANG ; Lijun MENG ; Yanli ZHU ; Jun KUAI ; Wenjing LI
Immunological Journal 2024;40(2):151-159
To detect interleukin-33(IL-33)level and investigate the effect of IL-33 signaling pathway on monocytes in patients with hepatitis B virus(HBV)-associated hepatocellular carcinoma(HCC),total of 31 HBV-HCC patients,33 chronic hepatitis B(CHB)patients and 21 normal controls were enrolled in the study.Peripheral blood was collected to isolate plasma and peripheral blood mononuclear cells(PBMC),then CD14+monocytes were purified by magnetic-activated cell sorting.Intrahepatic lymphocytes(IHL)were isolated from para-tumor tissues and tumor tissues of 11 HBV-HCC patients.IL-33 and soluble suppressor of tumorigenicity 2(sST2)levels in plasma were measured by enzyme-linked immunosorbent assay;ST2 expression in CD14+monocytes was investigated by flow cytometry.Recombinant human IL-33 was used to stimulate CD14+monocytes,then the cytokine secretion and HLA-DR proportion in CD14+monocytes were assessed.Furthermore,cytotoxicity of monocytes was also investigated.Data showed that plasma IL-33 level in CHB patients and HBV-HCC patients were lower than that in controls(P<0.01).Plasma sST2 level of HBV-HCC patients was higher than those of CHB patients and controls(P<0.01).ST2+CD14+proportion in PBMC from HBV-HCC patients was lower than those of from CHB patients and controls(P<0.000 1).ST2 mean fluorescence intensity(MFI)in PBC from HBV-HCC patients was lower than those from CHB patients and controls(P<0.0001).ST2+CD14+proportion in IHL was also lower in tumor tissues than that in para-tumor tissues(P<0.05);ST2 MFI in IHL was lower in tumor tissues than that in para-tumor tissues(P<0.05).As compared with controls,monocytes activity of HBV-HCC and CHB patients were lower,especially in tumor tissues,which was presented as downregulation of HLA-DR proportion,TNF-α,IL-6,IL-1β and granzyme B secretion(P<0.05).IL-33 stimulation did not affect ST2 level in CD14+monocytes(P>0.05).Both 0.1 ng/ml and 1 ng/ml of IL-33 stimulation elevated cytokine production and HLA-DR+CD14+monocytes percentage in CD14+monocytes from HBV-HCC patients(P<0.05).However,only 1 ng/ml of IL-33 stimulation promoted monocytes-induced target cell death(P<0.000 1).Taken together,monocytes activity is down-regulated in HBV-HCC patients,and IL-33 signaling pathway could enhance monocytes function in HBV-HCC patients.
5.The safety and protective effect on resting dry mouth of optimized dose optimization in clinical target volume Ⅱa in patients with N 0-N 1 nasopharyngeal carcinoma
Wenxuan HUANG ; Shengfu HUANG ; Siyu ZHANG ; Lanfang ZHANG ; Lijun WANG ; Juying LIU ; Yizhi GE ; Xia HE
Chinese Journal of Radiation Oncology 2024;33(5):397-404
Objective:To analyze the safety of reduced clinical target volume (CTV) irradiation of suspicious positive lymph nodes in IIa region in patients with N 0-N 1 nasopharyngeal carcinoma (NPC) and the protective effect of submandibular gland and long-term resting dry mouth, and to explore the diagnostic value of multimodal imaging for suspicious cervical lymph nodes. Methods:Clinical data of T 0-4N 0-1M 0 stage NPC patients admitted to Jiangsu Cancer Hospital from July 2015 to April 2017 were retrospectively analyzed. Clinical, radiation therapy planning, multimodal imaging and other relevant data were collected. All patients were treated with an optimized regimen of IMRT with a prophylactic radiation dose of 50.4 Gy (named as CTV50) for IIa region. Imaging characteristics and treatment response of suspicious lymph nodes were monitored by MRI, MRI-DWI, PET-CT and repeated enhanced positioning CT, etc. The dosimetry of the submandibular gland between optimized and standard dose plans (CTV50 vs. CTV60) was compared by paired t-test. The long-term dry mouth degree of the patients was evaluated using advanced radiation injury from Radiation Therapy Oncology Group (RTOG), Jiangsu Cancer Hospital Multi-dimensional Dry Mouth Evaluation Scale and summated xerostomia inventory (SXI). The difference of dry mouth degree was analyzed by rank-sum test. Results:A total of 106 patients were included in this study, including 149 cervical lymph node negative sides, 73 sides of which had ≤3 recognizable lymph nodes, and 76 of which were>3 in Ⅱa region. Among patients with N 1 stage, 63 patients underwent contralateral single neck area optimization, and 43 patients (N 0 stage and N 1 stage patients with retropharyngeal lymph node metastasis) underwent double-neck area optimization. A total of 109 suspicious lymph nodes with a short diameter of >5 mm were found on the largest cross section, of which 105 had clear portal structure. The ratio of long to short diameter was ≥1.5 in 93 cases, and the maximum standardized uptake value (SUV max) in PET-CT was ≥2.5 in 76 cases. No lymph node recurrence was found in the CTV optimized area. There was no significant difference in the average dose of GTV in tumor target area after optimization ( P>0.05), and the D mean and V 39 Gy in submandibular gland were significantly lower than those in unoptimized plan (both P<0.01). There was no significant difference in long-term dry mouth and resting dry mouth between patients with unilateral and bilateral optimization of submandibular gland (both P>0.05). Conclusions:The optimal program of CTV50 reduction irradiation in Ⅱa area of N 0-N 1 NPC patients is safe and effective. The submandibular gland has obvious dosimetric advantages, and patients have a good subjective response to resting dry mouth. The multimodal imaging tools such as enhanced CT, MRI-DWI and PET-CT should be performed to deliver individual evaluation and treatment for suspicious lymph nodes.
6.Treatment strategy and prognostic analysis of nasopharyngeal necrosis after first radical radiotherapy for nasopharyngeal carcinoma
Dan ZONG ; Wenxuan HUANG ; Yesong GUO ; Jing WEN ; Lijun WANG ; Lanfang ZHANG ; Lirong WU ; Cheng CHEN ; Shengfu HUANG ; Xia HE ; Zhenzhang CHEN
Chinese Journal of Radiation Oncology 2024;33(9):797-803
Objective:To investigate the treatment strategy and prognostic factors of nasopharyngeal necrosis after the first radical radiotherapy for nasopharyngeal carcinoma.Methods:Clinical data of 1020 patients with nasopharyngeal carcinoma undergoing radical intensity-modulated radiotherapy in Jiangsu Cancer Hospital from January 2013 to January 2022 were retrospectively analyzed. Nasopharyngeal necrosis was confirmed by nasopharyngeal MRI, electronic nasopharyngoscopy and biopsy. Patients with nasopharyngeal necrosis were treated with electronic nasopharyngoscope irrigation debridement, combined with systemic anti-infection and nutritional support therapy. Kaplan-Meier method was used to calculate the survival, and Cox regression analysis was used to analyze the relationship between clinical factors and patients' survival.Results:Nasopharyngeal necrosis occurred in 20 cases of 1020 nasopharyngeal carcinoma patients after the first radical intensity-modulated radiotherapy, with an incidence rate of 1.96%. Odd smell and headache were common in nasopharyngeal necrosis patients. All patients had locally advanced nasopharyngeal carcinoma at initial treatment, including 2 (10%) cases of T 3 stage and 18 (90%) cases of T 4 stage. Nasopharyngeal necrosis occurred in the primary nasopharyngeal lesions. According to the stages of nasopharyngeal necrosis, there were 6 (30%) cases of stage I, 14 (70%) cases of stage II and no stage III. The occurrence time of nasopharyngeal necrosis was from 2 to 24 months after radiotherapy, and the median time was 5 months. All 16 cases of nasopharyngeal necrosis were cured clinically after debridement and irrigation under nasopharyngoscope, systemic anti-infection and symptomatic support treatment. Among them, 9 cases had no necrotic cavity and complete healing and 7 cases had residual necrotic cavity. Four patients died of massive nasopharyngeal hemorrhage or due to the inability to nasopharyngeal irrigation. The 5-year survival rates were 37.5% and 85.7% in patients with and without internal carotid artery involvement ( P=0.008), and 25.0% and 77.8% in patients with and without diabetes mellitus ( P=0.016). Univariate Cox regression analysis showed that necrotic lesions involving internal carotid artery ( HR=5.80, 95% CI=1.14-29.38, P=0.034) and diabetes mellitus ( HR=10.24, 95% CI=1.19-88.04, P=0.034) were the influencing factors of overall survival. Conclusions:Nasopharyngoscope irrigation debridement combined with anti-inflammation and nutritional support treatment are effective interventions for nasopharyngeal necrosis after the first radical intensity-modulated radiotherapy in patients with nasopharyngeal carcinoma. The necrosis involving the internal carotid artery and diabetes mellitus are important factors affecting the survival of patients. Vascular invasion caused by vascular rupture is the main cause of death.
7.Values of serum tumor necrosis factor-α stimulated gene 6 protein and type ⅩⅥ collagen in predicting prognosis of patients with ulcerative colitis
Lijun MENG ; Lanfang ZHANG ; Lei QIN ; Wenjing LI ; Peijun SHEN ; Xu CHEN ; Xiaohe GUO
Journal of Clinical Medicine in Practice 2024;28(23):87-90
Objective To analyze the values of serum tumor necrosis factor-α stimulated gene 6 protein (TSG-6) and type ⅩⅥ collagen (col-16) in predicting the prognosis of patients with ulcerative colitis (UC). Methods A total of 160 patients with UC were enrolled as UC group, another 160 volunteers were selected as control group, and the levels of serum TSG-6 and col-16 were compared between the two groups. According to the modified Mayo scoring criteria, patients in the UC group were divided into mild group (
8.Effect of tegafur, gimeracil and oteracil potassium combined with oxaliplatin on gastric motility-related hormones, matrix metalloproteinase-2 and matrix metalloproteinase-9 in elderly patients with gastric cancer
Lanfang ZHANG ; Xu CHEN ; Jun KUAI ; Lei QIN ; Yan YANG ; Tingmin CHANG
Journal of Clinical Medicine in Practice 2024;28(12):57-60
Objective To investigate the effects of tegafur, gimeracil and oteracil potassium combined with oxaliplatin on gastric motility-related hormones, matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in elderly patients with gastric cancer. Methods A total of 128 elderly patients with gastric cancer were selected as the study subjects and randomly divided into control group (
9.The feasibility of individualized primary CTV for lateralized nasopharyngeal carcinoma
Siyu ZHANG ; Wenxuan HUANG ; Lijun WANG ; Juying LIU ; Lijun ZHAO ; Lirong WU ; Dejun WANG ; Wenjing XU ; Yesong GUO ; Pengwei YAN ; Lanfang ZHANG ; Zhenyu ZHAI ; Shengfu HUANG ; Xia HE
Chinese Journal of Radiation Oncology 2023;32(8):675-682
Objective:To investigate the feasibility of individualized primary clinical target volume (CTV) delineation in intensity-modulated radiotherapy for nasopharyngeal carcinoma (NPC).Methods:Clinical data of 87 consecutive patients newly diagnosed with lateralized NPC in Jiangsu Cancer Hospital between October 2016 and February 2018 were retrospectively analyzed. Lateralized NPC is defined as tumor invasion not exceeding the contralateral wall. According to the tumor spread, the primary CTV was optimized as follows: CTV2 only covered the medial part of the contralateral pterygopalatine fossa, whereas the contralateral foramen oval was not included; on the level of parapharyngeal space, the contralateral side of CTV only covered the posterior lateral lymph nodes, whereas the contralateral internal jugular vein was not regularly covered. Failure patterns and 5-year survival [local control rate (LCR), progression-free survival (PFS) and overall survival (OS)] were evaluated by Kaplan-Meier method. Paired t-test and rank-sum test were used to analyze the dose variation in the optimized region and adverse reactions. Results:The median follow-up time was 59.5 months. The 5-year LCR, PFS, and OS were 98.9%, 86.5% and 92.1%, respectively. There was no local recurrence in the optimized area of CTV. Dosimetric comparison results showed that the doses of parotid gland, temporal lobe, cochlea and middle ear on the contralateral side were reduced by 13.45%, 9.14%, 38.83%, and 29.36%, respectively. Four cases (4.6%) developed grade 3 hearing loss, all on the ipsilateral side. The optimized scheme significantly alleviated the hearing loss on the contralateral side compared to that on the ipsilateral side ( P<0.001). Other grade 3 late adverse reactions included cranial nerve injury, subcutaneous fibrosis in the neck and visual impairment, with 1 case each. Conclusion:Individualized primary CTV for lateralized NPC is feasible and safe, with obvious dosimetric advantages and reduced adverse reaction rate, which is worthy of clinical promotion.
10.Detection of early gastric cancer in white light imagings based on region-based convolutional neural networks
Jing Jin ; Qianqian Zhang ; Bill Dong ; Tao Ma ; Xi Wang ; Xuecan Mei ; Shaofang Song ; Jie Peng ; Aijiu Wu ; Lanfang Dong ; Derun Kong
Acta Universitatis Medicinalis Anhui 2023;58(2):285-291
Objective :
To develop an endoscopic automatic detection system in early gastric cancer (EGC) based on a region-based convolutional neural network ( Mask R-CNN) .
Methods :
A total of 3 579 and 892 white light images (WLI) of EGC were obtained from the First Affiliated Hospital of Anhui Medical University for training and testing,respectively.Then,10 WLI videos were obtained prospectively to test dynamic performance of the RCNN system.In addition,400 WLI images were randomly selected for comparison with the Mask R-CNN system and endoscopists.Diagnostic ability was assessed by accuracy,sensitivity,specificity,positive predictive value ( PPV) , and negative predictive value (NPV) .
Results :
The accuracy,sensitivity and specificity of the Mask R-CNN system in diagnosing EGC in WLI images were 90. 25% ,91. 06% and 89. 01% ,respectively,and there was no significant statistical difference with the results of pathological diagnosis.Among WLI real-time videos,the diagnostic accuracy was 90. 27%.The speed of test videos was up to 35 frames / s in real time.In the controlled experiment, the sensitivity of Maks R-CNN system was higher than that of the experts (93. 00% vs 80. 20% ,χ2 = 7. 059,P < 0. 001) ,and the specificity was higher than that of the juniors (82. 67% vs 71. 87% ,χ2 = 9. 955,P<0. 001) , and the overall accuracy rate was higher than that of the seniors (85. 25% vs 78. 00% ,χ2 = 7. 009,P<0. 001) .
Conclusion
The Mask R-CNN system has excellent performance for detection of EGC under WLI,which has great potential for practical clinical application.


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