1.A single-arm prospective study on induction chemotherapy and subsequent comprehensive therapy for advanced hypopharyngeal squamous cell carcinoma: report of 260 cases in a single center
Yifan YANG ; Ru WANG ; Jugao FANG ; Qi ZHONG ; Zhigang HUANG ; Xiaohong CHEN ; Shurong ZHANG ; Junmao GAO ; Shuling LI ; Pingdong LI ; Lizhen HOU ; Xuejun CHEN ; Hongzhi MA ; Ling FENG ; Yang ZHANG ; Shizhi HE ; Meng LIAN ; Shuzhou LIU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2020;55(12):1143-1153
Objective:To study the significance of induction chemotherapy and subsequent comprehensive therapy for overall survival rate (OS) and larynx dysfunction-free survival rate (LDFS) in patients with advanced hypopharyngeal carcinoma.Methods:Patients who met the inclusion criteria with the diagnoses of advanced hypopharyngeal carcinoma between 2011 and 2017 received 2 or 3 cycles of TPF regimen induction chemotherapy. Patients who attained complete response (CR) received radical chemotherapy. Patients who attained partial response (PR) and the reduction of tumor volume was more than 70% were defined as large PR and received concurrent chemoradiotherapy. When the tumor volume reduction of PR patients was less than 70%, they were defined as small PR. (CR+large PR) group was defined as effective group. Patients who did not reach CR and large PR were defined as uneffective group and underwent radical surgery and received adjuvant radiotherapy as appropriate after the surgery. The end points of the study were OS, progression-free survival (PFS) and LDFS. Chi-square (χ 2) test was used for correlation analysis. Survival analysis was performed by the Kaplan-Meier method with a Log-rank test. Cox proportional hazards model was used for univariate and multivariate survival analysis. Results:A total of 260 patients were enrolled in the study. The follow-up period ranged from 5 to 83 months, with an average of 24.7 months. The 3-year and 5-year OS rate was 46.0% and 32.6%, respectively. The 3-year and 5-year PFS rate was 41.0% and 26.6%, respectively. The 3-year and 5-year LDFS rate was 37.9% and 24.8%, respectively. Poor outcome of induction chemotherapy, advanced N stage, strong positive Ki-67 immunohistochemistry (all P<0.001) were negative prognostic factors. The advanced clinical stage was positively related to the poor outcome of induction chemotherapy ( P=0.015). There was no significant difference in OS and PFS between the large PR group and the small PR group (all P>0.005). Conclusion:TPF regimen induction chemotherapy and subsequent comprehensive therapy for patients with advanced hypopharyngeal carcinoma may improve the quality of life of patients, with high OS rate and LDFS rate.
2. Study on the association between the efficacy of peg-IFN and the complexity of TP and RT in chronic hepatitis B
Tianlin QI ; Xingyue WANG ; Chongping RAN ; Weihua CAO ; Lu ZHANG ; Yao LU ; Hongxiao HAO ; Shuling WU ; Ruyu LIU ; Min CHANG ; Leiping HU ; Minghui LI ; Yao XIE
Chinese Journal of Experimental and Clinical Virology 2019;33(1):74-78
Objective:
To explore the association between the efficacy of peg-IFN and the complexity of TP and RT regions of hepatitis B virus (HBV) in chronic hepatitis B.
Methods:
Patients with HBeAg positive, HBV DNA positive chronic hepatitis B were given peg-interferon 180 μg once a week for subcutaneous injection, and baseline information was collected from baseline and after 12 weeks’ treatment. The baseline HBV DNA TP and RT fragments were amplified, database, high-throughput sequencing, and the average genetic distance calculation.
Results:
Data of 108 patients were analyzed by logistic regression. RT area fragment Markov distance and TP area fragment Shannon quotient for HBV DNA response were calculated. ALT level is good for HBeAg response. HBsAg level is bad for HBsAg response.
Conclusions
The complexity of the baseline TP and RT regions may be associated with the efficacy of peg-interferon therapy for CHB.
3. Natural killer cells function in acute and chronic hepatitis B patients
Weihua CAO ; Shuling WU ; Chongping RAN ; Tianlin QI ; Xingyue WANG ; Xiaojing QU ; Dan ZHANG ; Lu ZHANG ; Yao LU ; Hongxiao HAO ; Min CHANG ; Leiping HU ; Ruyu LIU ; Yunzhong WU ; Min YANG ; Wenhao HUA ; Shunai LIU ; Minghui LI ; Yao XIE
Chinese Journal of Experimental and Clinical Virology 2018;32(1):21-26
Objective:
To investigate the differences in frequency and function of natural killer cells (NK) between chronic hepatitis B (CHB) and acute hepatitis B (AHB).
Methods:
Patients with AHB and those with CHB in immune active (IA) phase were enrolled. The frequencies of NK, CD56dimNK, CD56brightNK and the expression of functional molecules IFNAR2 and NKp46 on the surface of NK cells were detected respectively among patients with CHB in IA phase, patients with AHB, and those recovered from AHB. At the same time, their correlations with ALT, HBV DNA and HBV markers were analyzed.
Results:
Between IA and AHB, the frequencies of NK cells and NKp46dim NK cells in AHB cases were significantly lower than those in IA cases, but the frequency of NKp46high NK cells in AHB was higher than that in IA. For patients who recovered from AHB, the frequency of NK cells and NKp46dim NK cells increased; the varied ranges of frequencies of CD56dimNK, IFNAR2+ NK and NKp46+ NK cells were on the rise, while the frequency of NKp46high NK cells decreased after the recovery from AHB, and the varied ranges of CD56brightNK and IFNAR2MFI, NKp46MFI decreased. In AHB, HBVDNA loads were positively correlated with ALT levels. Before and after the recovery of AHB: ΔHBV DNA and ΔALT, Δ NK/LY (%) were positively correlated; ΔALT and ΔNKp46highNK/NK(%), ΔNKp46MFI, ΔIFNAR2MFI were positively correlated.
Conclusions
In CHB immune active phase, the activity of peripheral blood NK cells was too weak to remove the virus, but NK cells play an important role in eliminating the viruses and mediating liver tissue inflammation in AHB.
4. Re-treatment with peginterferon-ribavirin and direct antiviral agents of patients with chronic hepatitis C after failure of intensified treatment
Yao LU ; Hongxiao HAO ; Ge SHEN ; Shuling WU ; Ruyu LIU ; Leiping HU ; Min CHANG ; Weihua CAO ; Xinyue WANG ; Chongping RAN ; Tianlin QI ; Yunzhong WU ; Min YANG ; Lu ZHANG ; Minghui LI ; Yao XIE ; Daozhen XU
Chinese Journal of Experimental and Clinical Virology 2018;32(1):66-69
Objective:
To explore the persistent viral response rate (SVR) in patients with refractory chronic hepatitis C after interferon (IFN) (peginterferon 360 μg qw) and ribavirin (PR) therapy failure. The SVR of patients with refractory chronic hepatitis C was improved by PR combined with direct antiviral agents (DAA) and proper extension of the course of therapy was applied.
Methods:
Seventeen cases of refractory chronic hepatitis C after IFN(peginterferon 360 μg qw) and ribavirin therapy failure were given PR combined with DAA treatment. The side effects were observed and corresponding adjustments were made on drug dosage, and SVR was recorded.
Results:
The 17 cases completed the whole course of treatment with PR combined with DAA for 24 weeks. All the 17 patients obtained rapid viralogical response (RVR) and SVR. After treatment, the SVR rate was 100% in patients including those with virologic relapse, retreated or previously non-responsive patients with refractory chronic hepatitis C. The adverse reaction of PR combined with DAA 24 weeks was generally mild.
Conclusions
The use of PR combined with DAA re-treatment in patients with refractory chronic hepatitis C can achieve SVR and shorten the treatment time. PR combined with DAA re-therapy is one of effective treatments to improve the rate of sustained viral response in patients with refractory chronic hepatitis C.
5. Plasmacytoid dendritic cells and CD4+ T helper cells function in acute and chronic hepatitis B patients
Weihua CAO ; Chongping RAN ; Tianlin QI ; Xingyue WANG ; Xiaojing QU ; Dan ZHANG ; Lu ZHANG ; Yao LU ; Shuling WU ; Hongxiao HAO ; Min CHANG ; Leiping HU ; Ruyu LIU ; Yunzhong WU ; Min YANG ; Wenhao HUA ; Shunai LIU ; Minghui LI ; Yao XIE
Chinese Journal of Experimental and Clinical Virology 2017;31(6):487-491
Objective:
To investigate the differences in function of plasmacytoid dendritic cells (pDC) and CD4+ T helper cells (CD4+ Th cells) between acute hepatitis B (AHB) and chronic hepatitis B (CHB).
Methods:
In this study, patients with AHB and those with CHB in immune active (IA) phase were enrolled. The frequencies of pDC, CD86+ pDC, CD4+ T cells and their subsets, surface functional molecules were detected respectively among patients with chronic HBV infection in IA phase, patients with AHB, those recovered from AHB. Meanwhile, their correlations with ALT, HBV DNA and HBV markers were analyzed.
Results:
The ALT level in AHB was significantly higher than that in IA, and inflammation was more obvious in AHB. Between IA and AHB, CD86+ pDC frequency and the mean fluorescence intensity of functional molecule CD86 (CD86MFI) were higher in IA than those in AHB, but the frequency of CD4+ T cells in AHB was higher than that in IA. For patients who got over AHB, the frequency of CD86+ pDC increased; Th1 were on the rise, while the frequencies of CD4+ T and Th2 decreased after the recovery of AHB, and Th2 / Th1 ratio decreased..In AHB, HBVDNA loads were positively correlated with ALT levels and Th2 frequencies.
Conclusions
In CHB immune active phase, CD86+ pDC with stimulating function played an important role, but the cellular immune response of CD4+ T cells decreased. In AHB inflammatory stage, CD4+ T cells played a strong cellular immune response, which result ed in viral clearance. Th2 cells regulation of CD4+ T cells played a dominant role, which was involved in the inflammatory response, and the cytotoxic role of Th1 cells during the recovery period was dominant, playing a strong cellular immune response, then the virus were completely eliminated.
6. Changes in peripheral blood during the antiviral treatment with Peg-IFNα-2 a and ribavirin for patients with chronic hepatitis C and the relationship between the changes and effect
Zhenzhen LI ; Hongxiao HAO ; Lu ZHANG ; Yao LU ; Weihua CAO ; Xingyue WANG ; Chongping RAN ; Tianlin QI ; Shuling WU ; Ge SHEN ; Ru LIU ; Min CHANG ; Leiping HU ; Minghui LI ; Yao XIE
Chinese Journal of Experimental and Clinical Virology 2017;31(6):545-548
Objective:
To observe the changes of peripheral blood image of chronic hepatitis C (CHC) patients treated with pegylated interferon (Peg-IFN) and ribavirin, and explore the relationship between the changes and serum virological respose (SVR).
Methods:
Patients with CHC treated with Peg-IFN α-2 a and ribavirin in the Second Division of Liver Disease in Beijing Ditan Hospital were monitored for peripheral blood cells routine examination and Liver function, kidney function, thyroid function at baseline and week 2, 4, 8, 12, 24, 36, 48, and week 12, 24, 48 after the end of treatment for chronic hepatitis C, and HCV RNA.
Results:
The decrease of peripheral blood cell counts began to appear at week 2 of treatment. For CHC patients without cirrhosis, white blood cells, lymphocyte, hemoglobin and platelets at week 2, while minimum values were seen at week 36, and the neutrophils reached the minimum value to at week 24. Significant recovery of the peripheral blood changes was seen at the end of treatment (48 weeks), and reached pre-treatment levels at week 48 after the end of treatment. For CHC patients with cirrhosis, white blood cells, lymphocytes, hemoglobin and platelets significantly decreased at week 2, while neutrophils reached a minimum value at 2 weeks. And hemoglobin and platelets reached a minimum value at 24 weeks, and the white blood cells reached the minimum value at weeks 24-36 besides lymphocyte reached the minimum value at week 36. Significant recovery was seen at the end of treatment (48 weeks), and the blood cell counts reached pre-treatment levels at 48 weeks after the end of treatment. For patients with CHC, hemoglobin decreased by more than 27.47% at week 4, which means that the patient would have a predictive significance for SVR, as well as the of PLT reduction by more than 36.96% at week 8.
Conclusions
During the treatment with Peg-interferon and ribavirin, the variation of blood picture has some predicting effect, which predicts the result of antiviral treatment.
7. Protectivity of hepatitis B surface antibody in children between 1 and 3 years after successful blocking of mother-to-child transmission
Weihua CAO ; Ying ZHNAG ; Minghui LI ; Chongping RAN ; Tianlin QI ; Xingyue WANG ; Yuhong HU ; Mingshu ZHOU ; Lu ZHANG ; Yao LU ; Shuling WU ; Ge SHEN ; Hongxiao HAO ; Min CHANG ; Leiping HU ; Ruyu LIU ; Wenhao HUA ; Wei YI ; Yao XIE
Chinese Journal of Experimental and Clinical Virology 2017;31(5):401-404
Objective:
To investigate the change of hepatitis B surface antibody (HBsAb) titer and its long-term protection and infection rates between 1 and 3-year-old children whose mothers were chronic hepatitis B pregnant woman with HBeAg positive and high viral load after successful blocking of mother-to-child transmission.
Methods:
One-year-old children whose mothers were hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) positive, with HBV DNA≥106IU/ml were enrolled, then were followed up till 3 years old, and tested the five serological markers of hepatitis B and biochemical parameters at the age of one and three years respectively, and analyzed HBsAb titer, positive rate, negative rate and infection rate of 1 to 3-year-old children without enhanced vaccination; meanwhile, data of HBsAb titers at the age of 7 months were collected HBsAb titer, positive rate, and negative rate were analyzed.
Results:
Totally 264 1-year-old children were enrolled into the study, including 178 children without enhanced vaccination between seven months and 1 year of age, and 114 children without enhanced vaccination between 1 year and 3 years of age. Our result showed that there were no infected children at the age between 1 and 3 years. HBsAb titer decreased from 7 months to 1 year old and dropped from 1 000 IU/L to 509.43 IU/L (
8. Changes of peripheral blood during the antiviral treatment with Peg-IFNα-2 a for patients with chronic hepatitis B and the relationship between the changes and effect
Zhenzhen LI ; Shuling WU ; Lu ZHANG ; Yao LU ; Weihua CAO ; Xingyue WANG ; Chongping RAN ; Tianlin QI ; Hongxiao HAO ; Ge SHEN ; Hongyu LIU ; Min CHANG ; Leiping HU ; Minghui LI ; Yao XIE
Chinese Journal of Experimental and Clinical Virology 2017;31(5):446-449
Objective:
To observe the changes of peripheral blood picture of CHB with Peg-IFN, and explored the relationship between the changes and decline of HBV DNA, clearance of HBsAg.
Methods:
Patients with CHB treated with Peg-IFN α-2 a in the Second Division of Liver Disease in Beijing Ditan Hospital were monitored for blood routine examination and Liver function, kidney function, thyroid function of baseline and weeks 2, 4, 8, 12, 24, 36, 48, and weeks 12, 24, and 48 after the end of treatment for chronic hepatitis B, and HBV DNA, HBsAg.
Results:
The decrease of peripheral blood cells began to occur at week 2 of treatment. For CHB with HBeAg negative patients, white blood cells, lymphocyte, neutrophils, hemoglobin and platelets significantly decreased at 2 weeks, while a minimum value occurred at 48 weeks. The recovery was obvious at the end of treatment (48 weeks), and reached pre-treatment levels at 48 weeks after the end of treatment. For CHB with HBeAg positive patients, white blood cells, neutrophils, hemoglobin and platelets significantly decreased at 2 weeks, while a minimum value was found at 36-48 weeks. The recovery was obvious at the end of treatment (48 weeks), and reached pre-treatment levels at 48weeks after the end of treatment. For patients with CHB, hemoglobin declined by more than13.64% at 36th week, which means that the patient would have a predictive significance for decrease of HBV DNA, and drops of more than 0.33% at 2nd week means that the patient would have a predictive significance for clearance of HBsAg.
Conclusions
During the treatment with interferon, the variation regularity of blood picture for predicting result have a certain effect, which may help predict and monitor the change of blood picture in clinical work.
9.Determination of Chlorinated Persistent Organic Pollutants in Infant Hair by Gas Chromatography_High Resolution Mass Spectrometry
Shuling SONG ; Xiaojian HU ; Peng QI ; Song LI ; Ling TONG ; Qin TIAN ; Xiaodong MA
Chinese Journal of Analytical Chemistry 2015;(1):49-54
Infant hair is a good medium to assess the cumulative exposure level of infant in the mother ' s body. Chlorinated persistent organic pollutants were ubiquitous and with the highest volume concentration in the human body. In this experiment, 20 infant hairs were collected from Beijing. The sample was overnight incubated in HCl, extracted with the mixture of hexane and dichloromethane, and cleaned up by a cartridge filled with alumina and acidified silica. The final eluate was concentrated, and 16 kinds of typical chlorinated persistent organic pollutants were detected with gas chromatography_high resolution mass spectrometry ( HRGC_MS). The results showed that the detection limit of the target compounds in sample was 1. 00-2. 50 μg/kg, the recovery of surrogate in all samples was more than 67 . 6%, and the range of recoveries for target compounds in spiked sample was 62. 5%-92. 3%. The positive rate is 100% for hexachlorobenzene,β_HCH and p, pˊ_DDE, 85% for γ_HCH, 50% for PCB28, and 40% for PCB52. The concentrations of Hexachlorobenzene, HCHs, DDTs and PCBs were 5. 48-8. 40 μg/kg, 3. 86-27. 1 μg/kg, 1. 16-18. 3 μg/kg and 2. 20-22. 1 μg/kg, respectively. The average concentrations were 7. 84 μg/kg for hexachlorobenzene, 6. 93 μg/kg for HCHs, 5. 53 μg/kg for DDTs, and 3. 44 μg/kg for PCBs. The method and the analysis results can be used to evaluate the accumulation level and cumulative exposure level of 16 target compounds for fetal in motherˊs body.
10.Negative interference by calcium dobesilate in uricase-peroxidase coupled assays of serum uric acid
Xiuzhi GUO ; Jiangtao ZHANG ; Li′an HOU ; Jie WU ; Songlin YU ; Huiling FANG ; Xinqi CHENG ; Liangyu XIA ; Lin ZHANG ; Zhihong Qi ; Shuling CHI ; Dawei TONG ; Yingyin HAO ; Ling QIU
Chinese Journal of Laboratory Medicine 2015;(9):600-604
Objective To assess the interference by calcium dobesilatein 7 peroxidase-baseduric acid assays and to determine its clinical significance.Methods In the in vitro experiments, uric acid in pooled serum with final concentrations of calcium dobesilate additions (0, 2, 4, 8, 16, 32, and 64μg/ml) were measured by 7 peroxidase-based assays.Percent Bias (%) was calculated relative to the drug-free specimen.In the in vivo experiments, changes in serum uric acid and calcium dobesilate concentrations were observed before and after calcium dobesilate administration ( baseline, 0 h, 1 h, 2 h, 3 h, 4 h, 6 h ) involunteers.The interference in different assays was assessed compared with LC-IDMS/MS method. Calcium dobesilate levels in 40 specimens from those taking calcium dobesilate were measured by HPLC method.Of the 40 specimens, 10 were selected to analyse the levels of uric acid by both peroxidase and UV measurement method to assess the impact in clinical status.Results In the in vitro study, concentrations of uric acid measured by 7 peroxidase-based assays were reduced by -6.3%to -21.2%compared with drug-free serum, when theconcentration of calcium dobesilate was16μg/ml.In the in vivo study, comparedto UA levels at 0 h, the biasesof serum uric acid determined by peroxidase method after calcium dobesilate administration(1 h, 2 h, 3 h, 4 h, 6 h) were of -3.33%, -6.79%, -7.49%, -6.07%, -4.09%, respectively.The observed uric acid concentrations for 8 participants measured by enzymatic assays were inhibited by -3.75% to -6.89% at 0 hour and by -16.9% to-22.22% at 2 hours relative to the concentrations measured by the LC-IDMS/MS method. Conclusions Calcium dobesilate produced a clinically significant negative interference with uric acid in all peroxidase-based uric acid assays,which may result in false evaluation of uric acid level in clinical status.Significant differences in the degree of interference were observed among the assays.

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