1.A phase Ⅱ clinical study of the efficacy and safety of antaitasvir phosphate combined with yiqibuvir for the treatment of chronic hepatitis C in adults
Lai WEI ; Hongxin PIAO ; Jinglan JIN ; Shufen YUAN ; Xuan AN ; Jia SHANG ; Wenhua ZHANG ; Jiabao CHANG ; Tong SUN ; Yujuan GUAN ; Bo NING ; Jing ZHU ; Wentao GUO ; Qingwei HE ; Lin LUO ; Yulei ZHUANG ; Hongming XIE ; Yingjun ZHANG
Chinese Journal of Hepatology 2024;32(7):637-642
Objective:To evaluate the efficacy and safety of antaitasvir phosphate 100 mg or 200 mg combined with yiqibuvir for 12 weeks in patients with various genotypes of chronic hepatitis C, without cirrhosis or compensated stage cirrhosis.Methods:Patients with chronic hepatitis C (without cirrhosis or compensated stage cirrhosis) were randomly assigned to the antaitasvir phosphate 100 mg+yiqibuvir 600 mg group (100 mg group) or the antaitasvir phosphate 200 mg+yiqibuvir 600 mg group (200 mg group) in a 1∶1 ratio. The drugs were continuously administered once a day for 12 weeks and observed for 24 weeks after drug withdrawal. The drug safety profile was assessed concurrently with the observation of the sustained virological response (SVR12) in the two patient groups 12 weeks following the drug cessation. The intention-to-treat concept was used to define as closely as possible a full analysis set, including all randomized cases who received the experimental drug at least once. The safety set was collected from all subjects who received the experimental drug at least once (regardless of whether they participated in the randomization group) in this study. All efficacy endpoints and safety profile data were summarized using descriptive statistics. The primary efficacy endpoint was SVR12. The primary analysis was performed on a full analysis set. The frequency and proportion of cases were calculated in the experimental drug group (antaitasvir phosphate capsules combined with yiqibuvir tablets) that achieved "HCV RNA
2.Study on the mechanism of the effect of endothelial progenitor cell injury-derived microparticles on endothelial progenitor cells
Yiping MA ; Mijiti ABUDUREHEMAN ; Yujuan YUAN ; Yisimitila TUERSUNAYI ; Aihemati ABULAJIANG ; Nijiati MUYESAI
Chongqing Medicine 2023;52(23):3538-3545
Objective To investigate the effects of endothelial progenitor cells(EPC)-derived microp-articles(MPs)with different injury treatments on EPC.Methods EPC cells were cultured and EPCs were i-dentified by flow cytometry.EPCs were treated with high glucose(HG)and tumor necrosis factor(TNF)-a recombinant protein,and MPs were extracted.The structural changes of microtubules,Golgi bodies and other organelles in EPC were observed by transmission electron microscopy.MTT assay was used to detect cell pro-liferation.Cell scratch assay was used to evaluate cell migration ability.Cell lumen formation assay was used to detect lumen formation.The expression levels of endothelial nitric oxide synthase(eNOS),silent informa-tion regulator 1(SIRT1),rat sarcoma(RAS)and extracellular regulated protein kinase(ERK)in EPC after different treatments were detected by quantitative real-time fluorescence PCR(qPCR)and Western blot.Re-sults Compared with the control-EPC-MPs group,the microtubule structure of the HG-EPC-MPs group and the TNF-α-EPC-MPs group was complete,the length was shortened,and the Golgi structure was relatively complete.Compared with the control-EPC-MPs group,the proliferation rate of EPC in the HG-EPC-MPs group and the TNF-α-EPC-MPs group was down-regulated,the cell migration ability was decreased,and the tube formation was decreased(P<0.05).Compared with the control-EPC-MPs group,the mRNA and protein expressions of eNOS,SIRT1,RAS and ERK in the HG-EPC-MPs group and the TNF-α-EPC-MPs group were down-regula-ted(P<0.05).Conclusion HG and TNF-α mediated MPs derived from EPC injury may change the structure of organelles in EPC by regulating the expression of SIRT1/ERK1 pathway proteins,thus affecting the biolog-ical function of EPC.
3.Janus kinase inhibitors for the treatment of five children with severe alopecia areata
Yuanxiang LIU ; Yuan LIANG ; Xinrong ZHAO ; Yujuan SUN ; Lin MA ; Zigang XU
Chinese Journal of Dermatology 2023;56(9):849-852
Objective:To evaluate the efficacy of Janus kinase (JAK) inhibitors in the treatment of 5 children with severe alopecia areata, especially those with complicated nail damage.Methods:A total of 5 children with severe alopecia areata were enrolled and treated with oral JAK inhibitors (tofacitinib or baricitinib). The improvement of hair loss was assessed by using the severity of alopecia tool (SALT) at 12, 24, 36, and 48 weeks after the start of treatment. For 3 children with complicated nail damage, the improvement of diseased nails and toenails was evaluated by using the modified nail psoriasis severity index after treatment. During the treatment, adverse reactions were monitored.Results:The 5 children with severe alopecia areata were aged 2 - 11 years, with the disease duration ranging from 5 to 120 months, and the treatment with JAK inhibitors lasted 24 - 48 weeks. After 12-week treatment, 2 children achieved a 50% improvement in SALT (SALT50) ; after 24-week treatment, 3 achieved SALT95, and 1 achieved SALT75 and then withdrew baricitinib for personal reasons; after 36-week treatment, 3 achieved SALT99, and then received half-dose treatment; after 48-week treatment, 1, 1, 1 and 1 patient achieved SALT99, SALT83, SALT31, and SALT0, respectively, and 2 of them experienced gradually aggravated hair loss 1 - 2 months after the start of half-dose treatment. Among the 3 children with complicated nail damage, the improvement rates of nail severity index scores were 67.5%, 45.4%, and 25% respectively, and the improvement rates of toenail severity index scores were 42.5%, 71.4%, and 5% respectively after 12-week treatment; after 48-week treatment, the improvement rate of nail severity index scores were 100%, 100%, and 50% respectively, and the improvement rate of toenail severity index scores were 96.2%, 100%, 50% respectively. During the treatment, the uric acid level increased in 2 children, and one of them was accompanied by increased serum levels of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol; 1 suffered from respiratory tract infections twice during the treatment, and was recovered after symptomatic treatment; there were no adverse reactions leading to drug withdrawal.Conclusion:JAK inhibitors can be used as a treatment option for severe alopecia areata in children.
4.Prevalence and genotyping of Cryptosporidium spp. and Giardia lamblia in dogs and cats from a pet hospital in Shanghai Municipality
Jing ZHANG ; Yuan QIN ; Yujuan SHEN ; Yaxue WANG ; Jianping CAO ; Yaxin SU ; Hua LIU
Chinese Journal of Schistosomiasis Control 2023;35(3):258-262
Objective To investigate the prevalence and genotypes of Cryptosporidium spp. and Giardia lamblia in dogs and cats from a pet hospital in Shanghai Municipality. Methods A total of 145 fresh fecal samples were collected from pet dogs and cats in a pet hospital in Shanghai Municipality during the period from November 2021 to June 2022, including 99 dog fecal samples and 46 cat fecal samples. The small subunit ribosomal ribonucleic acid (SSU rRNA) gene of Cryptosporidium and the triose phosphate isomerase (TPI) gene of G. lamblia were amplified using nested PCR assay, and the positive amplification products were sequenced from both directions. The sequence assembly was performed using the software Clustal X 2.1, and sequence alignment was conducted using BLAST. A phylogenetic tree was created with the Neighbor-Joining method using MEGA 11.0 to identify parasite species or genotype. Results The overall prevalence of Cryptosporidium and G. lamblia was 20.00% (29/145) in 145 pet dog and cat fecal samples, with the prevalence of 0.69% (1/145) and 19.31% (28/145) in Cryptosporidium and G. lamblia, respectively. G. lamblia was only detected in dog fecal samples, with prevalence of 18.18% (18/99), while the detection rates of Cryptosporidium and G. lamblia were 2.17% (1/46) and 21.74% (10/46) in cat fecal samples. Nucleotide sequence analysis showed that one Cryptosporidium positive sample was characterized as C. felis, and 28 G. lamblia positive samples were all characterized as Giardia assemblage A, which showed 100% sequence homology with human isolates of Giardia. Phylogenetic analysis revealed that the sequences obtained in this study belonged to the same branch with the reported Giardia assemblage A. Conclusions Cryptosporidium and G. lamblia infection was prevalent in pet dogs and cats from the study pet hospital in Shanghai Municipality, and there is a zoonotic risk for the species and genotype. Intensified surveillance of Cryptosporidium and Giardia infection is recommended in pets and their owners, and improved management of pet keeping is required.
5.Study on the normal value of cervical elasticity parameters of primiparas during pregnancy by transvaginal ultrasound
Yuan GAO ; Jianjun YUAN ; Yujuan GUO ; Zhaoling ZHU ; Xijun ZHANG ; Li WANG ; Lina WU ; Ruili WANG
Chinese Journal of Ultrasonography 2022;31(8):724-729
Objective:To investigate the normal parameter values of transvaginal E-Cervix cervical elastography of primipara and explore the correlation between E-Cervix parameters and gestational age.Methods:A total of 301 primiparas underwent E-Cervix by transvaginal ultrasound in Henan Provincial People′s Hospital from March 2019 to January 2021, they were divided into 6 groups according to generational weeks: group A (11-13 + 6W), group B (14-17 + 6W), group C (18-21 + 6W), group D (22-25 + 6W), group E (26-29 + 6W), group F (30-33 + 6W). Real-time E-Cervix parameters were obtained, including elasticity contrast index (ECI), hardness ratio (HR), internal ostium (IOS), and external ostium (EOS), strain ratio of the internal and external cervical ostium (IOS/EOS), and the correlations between E-Cervix parameters and the gestational week were analyzed. Results:The normal reference ranges of parameters ECI, IOS, EOS, HR and IOS/EOS were obtained, their 95% reference values in groups A to F were as follows: ECI (1.84-3.38, 2.13-4.50, 2.25-4.12, 2.06-3.96, 2.04-5.15, 2.36-5.53), HR (85.85%-88.72%, 77.31%-80.92%, 74.41%-78.50%, 71.13%-74.35%, 64.49%-68.56%, 63.57%-68.23%), IOS (0.12-0.21, 0.14-0.34, 0.14-0.31, 0.19-0.40, 0.19-0.56, 0.21-0.49), EOS (0.12-0.30, 0.14-0.34, 0.16-0.41, 0.20-0.39, 0.22-0.58, 0.22-0.54), IOS/EOS (0.55-1.12, 0.52-1.45, 0.56-1.26, 0.54-1.38, 0.54-1.52, 0.65-1.46). The differences of ECI, HR, IOS and EOS in different groups were statistically significant (all P<0.05). Spearman correlation analysis results showed that ECI, IOS, and EOS were positively correlated with gestational week( rs=0.524, 0.689, 0.609; all P<0.01). HR was negatively correlated with gestational week ( rs=-0.755, P<0.01). The regression equations of ECI, HR, IOS and EOS were Y=0.06X+ 52.214, Y=99.25-1.07X, Y=8.63E-3X+ 0.05, Y=7.94E-3X+ 0.1, respectively. Conclusions:The normal parameters values of E-TVES are summarized.It provides effective support in data for cervical evaluation in the preterm prediction and success of labor induction.
6.Clinical efficacy of apatinib combined with S-1 in the treatment of advanced esophageal cancer
Xuewei ZHANG ; Peiying SU ; Lei PENG ; Xin LU ; Lei YUAN ; Yujuan GAO
Journal of International Oncology 2021;48(1):30-34
Objective:To explore the efficacy of apatinib combined with S-1 capsule in the treatment of patients with advanced recurrent and metastatic esophageal cancer.Methods:A total of 140 patients with advanced esophageal cancer were selected as test subjects from January 2017 to January 2019 in Shandong Tai′an Cancer Prophylaction-Therapeutic Hospital. These patients were randomly divided into observation group (72 cases) and control group (68 cases) using random number table method. The patients in the observation group were treated with oral apatinib combined with S-1 chemotherapy, and the patients in the control group was only given S-1 chemotherapy. The short-term and long-term efficacy and adverse reactions of the two groups were observed.Results:The objective remission rates of the observation group was 38.9% (28/72), higher than that in the control group (22.1%, 15/68), with a statistically significant difference ( χ2=4.655, P=0.031). The disease control rate of the observation group was 88.9% (64/72), higher than that in the control group (61.8%, 42/68), and there was a significant difference between the two groups ( χ2=13.993, P<0.001). The median progression-free survival of the observation group and the control group was 5.9 months and 2.7 months respectively, the median overall survival was 14.8 months and 7.9 months respectively, and there were significant differences between the two groups ( χ2=5.477, P=0.026; χ2=6.083, P=0.014). The adverse reactions of the two groups were mild, grade 1-2, mainly including fatigue, leukopenia, hand-foot syndrome, hypertension and proteinuria, with incidences of 59.7% (43/72), 50.0% (36/72), 8.3% (6/72), 12.5% (9/72), 9.7% (7/72) in the observation group, and 51.5% (35/68), 57.4% (39/68), 17.6% (12/68), 4.4% (3/68), 4.4% (3/68) in the control group, there were no significant differences between the two groups ( χ2=0.965, P=0.326; χ2=0.760, P=0.383; χ2=2.708, P=0.100; χ2=2.919, P=0.088; χ2=0.794, P=0.373). Conclusion:Apatinib combined with S-1 is effective, safe and tolerable in the treatment of recurrent and metastatic esophageal cancer.
7.Relationship between blood pressure after early endovascular treatment and clinical prognoses in patients with acute large vessel occlusion stroke of anterior circulation
Junfeng XU ; Yujuan ZHU ; Xianjun HUANG ; Wenbing WANG ; Xiangjun XU ; Lili YUAN ; Youqing XU ; Ke YANG ; Qian YANG ; Zhiming ZHOU
Chinese Journal of Neuromedicine 2020;19(9):882-889
Objective:To explore the influence of blood pressure (BP) profiles 24 h after early endovascular treatment (EVT), including mean blood pressure and blood pressure variability, in clinical prognoses of patients with acute large vessel occlusion stroke (ALVOS) of anterior circulation 90 d after EVT.Methods:Clinical data and blood pressure profiles of patients with ALVOS of anterior circulation who received EVT in our hospital from July 2014 to February 2019 were prospectively collected. The 90-d modified Rankin scale (mRS) scores were used as clinical prognosis evaluation, and modified thrombdysis in cerebral infarction (mTICI) was used as evaluation criteria for recanalization of postoperative occlusive blood vessels. Multivariate Logistic regression analysis was used to determine the independent influencing factors for prognoses 90 d after EVT.Results:(1) Two hundred and sixteen patients were collected; 159 patients were with successful recanalization and 57 patients were with unsuccessful recanalization; 90 d after EVT, 95 patients (44%) had good prognosis and 121 patients (56%) had poor prognosis. As compared with patients in the good prognosis group, patients in the poor prognosis group had signficantly advanced age, signficantly higher proportion of patients with atrial fibrillation, signficantly higher baseline NIHSS scores, and signficantly lower baseline ASPECT scores ( P<0.05); and the differences of occlusion locus were statistically significant between patients from the good and poor prognosis groups ( P<0.05). Patients in the poor prognosis group had significantly higher baseline systolic blood pressure (SBP), mean SBP, max SBP, and significantly higher standard deviation, variable coefficient, and continuous variation of SBP, and statistically higher standard deviation, variable coefficient, and continuous variation of diastolic blood pressure (DBP) as compared with those in the good prognosis group ( P<0.05). Multivariable Logistic regression analysis showed that the standard deviation and continuous variation of SBP were independent influencing factors for clinical prognoses 90 d after EVT ( OR=1.116, 95%CI: 1.002-1.243, P=0.047; OR=1.116, 95%CI: 1.016-1.227, P=0.022). (2) In patients with successful recanalization, as compared with patients in the good prognosis subgroup, patients in the poor prognosis subgroup had signficantly advanced age, statistically higher proportions of patients with diabetes mellitus and atrial fibrillation and baseline NIHSS scores, and statistically lower baseline ASPECT scores ( P<0.05); and the differences of occlusion locus and first choices of treatment were statistically significant between patients in the good and poor prognosis subgroups ( P<0.05). Patients in the poor prognosis subgroup had significantly higher baseline SBP and max SBP, and significantly higher standard deviation, variable coefficient, and continuous variation of SBP, and statistically higher variable coefficient of DBP as compared with those in the good prognosis subgroup ( P<0.05). Multivariable Logistic regression analysis showed the standard deviation, variable coefficient, and continuous variation of SBP were independent influencing factors for clinical prognoses 90 d after EVT ( OR=1.164, 95%CI: 1.021-1.326, P=0.023; OR=1.191, 95%CI: 1.007-1.409, P=0.041; OR=1.141, 95%CI: 1.018-1.279, P=0.024). However, in patients with unsuccessful recanalization, there were no significant differences in blood pressure proliles between the good prognosis subgroup and poor prognosis subgroup ( P>0.05). Conclusion:The blood pressure variability 24 h after EVT is correlated with the clinical prognoses of patients with ALVOS of anterior circulation 90 d after EVT.
8.Real-world effectiveness and safety of OBT/PTV/r and dasabuvir for patients with chronic HCV genotype 1b infection in China:A multicenter prospective observational study
Jie YUSHENG ; Lin CHAOSHUANG ; Yuan JING ; Zhao ZHIXIN ; Guan YUJUAN ; Zhou YUANPING ; Zhou XIAOHUI ; Zhong BIHUI ; Ye YINONG ; Zhang LIHUA ; Tao LING ; Li JIANPING ; Zhang XIAOHONG ; Chong YUTIAN
Liver Research 2020;4(3):153-158
Background and aim:Real-world data on the effectiveness and safety of treatment with the direct-acting antiviral agent-based regimen are limited on the Chinese mainland.The aim of this study was to conduct a multicenter,prospective,real-world study of ombitasvir/paritaprevir/ritonavir(OBT/PTV/r)combined with dasabuvir(DSV)in hepatitis C virus(HCV)genotype 1b-infected non-cirrhotic or compensated cirrhotic Chinese adult patients. Materials and methods:Genotype 1b-infected patients were enrolled at eight sites in China.Patients received 25/150/100 mg of OBT/PTV/r once daily combined with 250 mg of DSV twice daily for 8 weeks or 12 weeks.Sustained virological response at 12 weeks post-treatment(SVR12)and the incidence of adverse events were assessed.We have also evaluated the effect of intensive questioning of patients who were overdue for SVR12 testing.Intention-to-treat(1TT)and modified 1TT(mITT)populations were used in the analysis. Results:One hundred forty patients were included,among whom 90.0%(126/140)were newly diag-nosed,9.3%(13/140)had compensated cirrhosis,92.9%(130/140)received 12 weeks of treatment,and 7.1%(10/140)received 8 weeks of treatment.In the mITT population,the virological response rate at week 4 was 96.4%(108/112),and at the end of treatment was 100%(102/102).Among these patients,139 patients completed 12 weeks of treatment,and 73 patients were followed-up.All followed-up patients achieved SVR12.There was no adverse event-related discontinuation.Serious adverse events during treatment were reported in two(1.4%)patients,and none were considered to be drug-related.Sixty-six(47.1%)patients did not return to receive the HCV RNA test at 12 weeks post-treatment. Conclusions:The rate of SVR12 was consistent with Phase Ⅲ clinical studies.OBT/PTV/r combined with DSV showed effectiveness in Chinese adult patients,and both tolerability and safety profile were favorable.However,patient compliance should be further improved in the real world.
9.Application of long non-coding RNA LincROR in the screening of ovarian cancer
Jingyun ZHANG ; Ting YUAN ; Yujuan LI ; Jing ZHOU ; Jingyan XIE ; Shuli ZHAO
Chinese Journal of Clinical Laboratory Science 2019;37(8):608-611
Objective:
To investigate the expression levels of long non-coding RNA LincROR in plasma and tissues of ovarian cancer patients and its value in the screening of ovarian cancer.
Methods:
The plasma samples from 30 healthy women, 56 cases of ovarian cysts, 23 cases of endometriosis, 38 cases of endometrial carcinoma, 35 cases of cervical cancer, 42 cases of ovarian cancer, 21 cases of ovarian cancer after operation and 26 cases of ovarian cancer after chemotherapy were collected, and the expression levels of LincROR in these samples were detected by quantitative PCR. The diagnostic value of LincROR in common clinical gynecological diseases was evaluated combined with clinical data.
Results:
The expression levels of LincROR in plasma of ovarian cancer patients (2.90± 4.42 ) were significantly higher than that in healthy women (0.23±0.28) and the patients with benign ovarian cysts (0.62±0.55, P < 0.01 ). The results of ROC curve analysis showed that the diagnostic value of plasma LincROR in the screening of breast cancer was better than that of CA125, CA199, CA153, AFP and CEA. The sensitivity and specificity of combined screening of LincROR and CA125 for ovarian cancer were 89.7% and 86.7%, respectively (AUCROC=0.918, 95% CI :0.817-0.973). In addition, the expression levels of plasma LincROR in the postoperative patients were significantly lower than that in the ovarian cancer patients without any treatment (0.50±1.72 vs 2.90±4.42, P <0.01). The ROC curve analysis showed that plasma LincROR was more sensitive than CA125 in evaluating the efficacy of chemotherapy for ovarian cancer (AUCROC: 0.866 vs 0.738).
Conclusion
LincROR is expected to be an ideal biomarker for the screening of ovarian cancer, and has potential clinical value in evaluating the efficacy of chemotherapy for ovarian cancer. Combination of LincROR with CA125 may improve the sensitivity and specificity of the screening of ovarian cancer
10. Real-world study of paritaprevir/ritonavir-ombitasvir combined with dasabuvir for the treatment of chronic hepatitis C 1b genotype infection in China
Yusheng JIE ; Jing YUAN ; Xiaohong ZHANG ; Yujuan GUAN ; Zhixin ZHAO ; Yutian CHONG ; Ling TAO ; Jianping LI ; Chaoshuang LIN
Chinese Journal of Hepatology 2019;27(2):123-127
Objective:
To evaluate the real-world safety and curative effect of ombitasvir combined with dasabuvir for the treatment of chronic hepatitis C 1b genotype infection in non-cirrhotic or compensated cirrhotic patients.
Methods:
A real-world research method was adopted, and the research was conducted at three medical centers of mainland China. Non- cirrhotic or compensated cirrhotic patients with HCV genotype 1b infection who were initially treated with IFN/PEG-IFN-alpha combined with ribavirin, and ombitasvir combined with dasabuvir for 8 or 12 weeks were taken. Sustained virological response (SVR) and the incidence of adverse events during treatment and follow-up were evaluated after 12 weeks of drug withdrawal at OBV/PTV/r 25/150/100mg once daily and DSV 250mg, twice daily. Median and range were used for description of non-normally distributed data.
Results:
80 cases of GT1b were included in this study. Of these 88.8% (71/80) were newly diagnosed, 12.5% (10/80) were compensated cirrhotic, 97.5% (78/80) received 12 weeks treatment, and 2.5% (2/80) received 8 weeks treatment. The rate of HCV RNA negative at EOT (end of treatment) was 100% (64/64). A total of 67 patients completed the treatment within 12 weeks, and 43 patients returned to the hospital for further consultations, and SVR12 was 100%(43/43). No patient discontinued the drugs because of an adverse event during treatment.
Conclusion
In the real world, Ombitasvir combined with dasabuvir for the treatment of chronic hepatitis C 1b genotype infection in China has 100% rates of EOT and SVR12 with well- tolerability and safety.

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