1.The levels of NK cells and Th cytokines predict the outcomes of assisted reproductive pregnancy in HR-HPV infected patients
Hailing WEN ; Haohui LI ; Lihua ZHOU
International Journal of Laboratory Medicine 2025;46(4):404-408
Objective To investigate the prediction of natural killer(NK)cells,and T helper cells(Th)cy-tokine levels for assisted reproductive pregnancy outcomes in high-risk human papillomavirus(HR-HPV)in-fected patients.Methods A total of 128 cases of HR-HPV infected patients who received assisted reproduc-tive treatment in a hospital from September 2021 to June 2023 were selected as the study objects,and were di-vided into normal pregnancy outcome group(n=87)and adverse pregnancy outcome group(n=41)accord-ing to their pregnancy outcomes.The clinical data,NK cell proportion,interleukin(IL)-2,IL-4,IL-6 and IL-10 levels before in vitro fertilization-embryo transfer treatment were collected and compared between the two groups.Spearman correlation analysis,univariate Logistic regression analysis and multiple Logistic regression analysis were used to screen out the risk factors for adverse pregnancy outcomes in HR-HPV infected patients receiving assisted reproduction.Receiver operating characteristic(ROC)curve and area under the curve(AUC)were used to evaluate the predictive efficacy of risk factors alone and in combination for adverse preg-nancy outcomes in HR-HPV infected patients undergoing assisted reproduction.Results The age of the ad-verse pregnancy outcome group was significantly higher than that of the normal pregnancy outcome group,and the difference was statistically significant(P<0.05).The proportion of NK cells and the level of IL-10 in the adverse pregnancy outcome group were significantly lower than those in the normal pregnancy outcome group,and the level of IL-6 was significantly higher than that in the normal pregnancy outcome group,with statistical significance(P<0.05).Spearman correlation analysis showed that age and IL-6 level of HR-HPV infection were positively correlated with adverse pregnancy outcome after assisted reproduction(r=0.582,0.341,P<0.001).The proportion of NK cells and the level of IL-10 were negatively correlated with adverse pregnancy outcomes after assisted reproduction(r=-0.459,-0.359,P<0.001).Multivariate Logistic re-gression analysis showed that the proportion of NK cells,low level of IL-10 and high level of IL-6 in HR-HPV infected persons were risk factors for adverse pregnancy outcomes after assisted reproduction(P<0.05).ROC curve analysis results showed that the AUC of NK cell ratio,IL-6 and IL-10 alone and in combination to predict adverse pregnancy outcome after assisted reproduction in HR-HPV infected patients were 0.784,0.711,0.660 and 0.876,respectively.The efficiency of combined prediction using the three indicators was higher than that of independent prediction(Z=3.006,3.211,3.716,P<0.05).Conclusion The levels of NK cells and Th cytokines have important clinical significance in the prediction of assisted reproductive pregnancy outcome in HR-HPV infected patients.
2.Effect of Tianzhi granule on neuroinflammation in rats with vascular dementia based on inflammatory response mediated by Nrf2/HO-1 signaling pathway
Ling LIAO ; Wen ZHENG ; Yuanya ZHANG ; Chen HUANG ; Na LIU ; Lihua YANG ; Hongbo YU
Chinese Journal of Immunology 2025;41(4):815-821,827
Objective:To explore inhibitory effect of Tianzhi granule on neuroinflammation in vascular dementia(VD)rats.Methods:Sixty rats were randomly divided into Sham group,VD group,TZG-L group and TZG-H group,with 15 rats in each group.Bilateral common carotid artery occlusion was used to construct VD rats model,Sham group was not ligated.Rats in TZG-L group and TZG-H group were gavaged with Tianzhi granule 5 g/kg,20 g/kg every day,while rats in Sham group and VD group were gavaged with same amount of normal saline for 8 weeks.Y-maze test was used to detect cognitive ability of rats;Nissl staining and FJC staining were used to assess neuronal damage;TUNEL staining was used to detect neuronal apoptosis;immunofluorescence staining and Western blot were used to detect Bcl-2,Bax,Caspase-3,NLRP3,ASC,Caspase-1,IL-1β,IL-18,TNF-α,Iba-1,GFAP,MPO,Nrf2,HO-1 protein levels in temporal cortex tissue.PC12 cells was divided into Control group,Glutamate group,TZG-L group and TZG-H group.Glutamate(20 μmol/L)was used to construct neuron injury model.TZG-L group and TZG-H group were added with Tianzhi granule 1 mg/ml,4 mg/ml.Neurons in each group were incubated for 48 h.CCK8 method and TUNEL staining were used to detect activity and apoptosis of neurons;immunofluorescence staining and Western blot were used to detect Bcl-2,Bax,Caspase-3,Nrf2,HO-1 protein levels in cells.Results:Compared with Sham group,cognitive ability of rats in VD group were decreased,TUNEL positive neurons ratio was increased,Bcl-2 level was decreased,Bax,Caspase-3,NLRP3,ASC,Caspase-1,IL-1β,IL-18,TNF-α,Iba-1,GFAP,MPO,Nrf2,HO-1 levels were increased(all P<0.05).Compared with VD group,cognitive ability of rats in TZG-L group and TZG-H group were increased,TUNEL positive neurons ratio was decreased,Bcl-2,Nrf2,HO-1 levels were increased,Bax,Caspase-3,NLRP3,ASC,Caspase-1,IL-1β,IL-18,TNF-α,Iba-1,GFAP,MPO levels were decreased(all P<0.05).Morphology of neurons in control group were normal;compared with control group,neurons in Glutamate group were swollen,activity of neurons was decreased,apoptosis rate was increased,Bcl-2 level was decreased,Bax,Caspase-3,Nrf2,HO-1 levels were increased(all P<0.05);compared with Glutamate group,cell damage in TZG-L group and TZG-H group were reduced,activity of neurons was increased and apoptosis rate was decreased,Bcl-2,Nrf2,HO-1 levels were increased,Bax,Caspase-3 levels were decreased(all P<0.05).Conclusion:Tianzhi granule can inhibit neuronal apoptosis and expression of NLRP3 inflammasome in VD rats,inhibit activa-tion of microglia/astrocytes and neutrophil infiltration,improve neuroinflammation of VD,which may play a role by activating Nrf2/HO-1 signaling pathway in neurons.
3.Influence and mediation effect of adolescent obesity on myopia risk:a cross-sectional and cohort analysis based on longitudinal study of Chengdu city from 2014 to 2023
Yanqun WEN ; Ya WEN ; Kefeng LI ; Lihua DI ; Li ZHAO ; Siqi LI
Journal of China Medical University 2025;54(3):204-207
Objective To investigate the relationships between adolescents'body mass index(BMI),blood pressure(BP),and myopia and provide a scientific basis for the formulation of myopia prevention and control measures.Methods Adolescent students who par-ticipated in physical fitness surveillance in Chenghua District,Chengdu,from 2014 to 2023 were selected as the study population.A cross-sectional study was conducted using multiple logistic regression,adjusting for age,sex,BP,and pulse as covariates.A Cox model was employed to examine the relationship between obesity and myopia.Additionally,for the 2023 dataset,characterized by the largest sample size and most complete data,a mediation analysis was performed with mean BP as the mediator.Results Annual cross-sectional analysis from 2014 to 2023 revealed a significant positive association between obesity and myopia,with OR and 95%CI of 1.16(1.10-1.22),1.15(1.08-1.21),1.19(1.12-1.26),1.11(1.04-1.18),1.10(1.05-1.15),1.10(1.05-1.16),1.07(1.03-1.12),1.10(1.05-1.15),1.12(1.07-1.17),and 1.11(1.06-1.15),respectively.Similarly,cohort analysis showed a significant positive association between obesity and myopia(HR=1.09,95%CI:1.01-1.19).Mediation analysis indicated that BP accounted for 21.2%of the total effect of obesity on myopia.Conclusion Obesity facilitates the onset of myopia,and weight reduction can help decrease the likelihood of latter.Furthermore,BP mediates the impact of obesity on myopia.Implementing BP-lowering interventions in obese populations may aid in the prevention of myopia.
4.Effect of Tianzhi granule on neuroinflammation in rats with vascular dementia based on inflammatory response mediated by Nrf2/HO-1 signaling pathway
Ling LIAO ; Wen ZHENG ; Yuanya ZHANG ; Chen HUANG ; Na LIU ; Lihua YANG ; Hongbo YU
Chinese Journal of Immunology 2025;41(4):815-821,827
Objective:To explore inhibitory effect of Tianzhi granule on neuroinflammation in vascular dementia(VD)rats.Methods:Sixty rats were randomly divided into Sham group,VD group,TZG-L group and TZG-H group,with 15 rats in each group.Bilateral common carotid artery occlusion was used to construct VD rats model,Sham group was not ligated.Rats in TZG-L group and TZG-H group were gavaged with Tianzhi granule 5 g/kg,20 g/kg every day,while rats in Sham group and VD group were gavaged with same amount of normal saline for 8 weeks.Y-maze test was used to detect cognitive ability of rats;Nissl staining and FJC staining were used to assess neuronal damage;TUNEL staining was used to detect neuronal apoptosis;immunofluorescence staining and Western blot were used to detect Bcl-2,Bax,Caspase-3,NLRP3,ASC,Caspase-1,IL-1β,IL-18,TNF-α,Iba-1,GFAP,MPO,Nrf2,HO-1 protein levels in temporal cortex tissue.PC12 cells was divided into Control group,Glutamate group,TZG-L group and TZG-H group.Glutamate(20 μmol/L)was used to construct neuron injury model.TZG-L group and TZG-H group were added with Tianzhi granule 1 mg/ml,4 mg/ml.Neurons in each group were incubated for 48 h.CCK8 method and TUNEL staining were used to detect activity and apoptosis of neurons;immunofluorescence staining and Western blot were used to detect Bcl-2,Bax,Caspase-3,Nrf2,HO-1 protein levels in cells.Results:Compared with Sham group,cognitive ability of rats in VD group were decreased,TUNEL positive neurons ratio was increased,Bcl-2 level was decreased,Bax,Caspase-3,NLRP3,ASC,Caspase-1,IL-1β,IL-18,TNF-α,Iba-1,GFAP,MPO,Nrf2,HO-1 levels were increased(all P<0.05).Compared with VD group,cognitive ability of rats in TZG-L group and TZG-H group were increased,TUNEL positive neurons ratio was decreased,Bcl-2,Nrf2,HO-1 levels were increased,Bax,Caspase-3,NLRP3,ASC,Caspase-1,IL-1β,IL-18,TNF-α,Iba-1,GFAP,MPO levels were decreased(all P<0.05).Morphology of neurons in control group were normal;compared with control group,neurons in Glutamate group were swollen,activity of neurons was decreased,apoptosis rate was increased,Bcl-2 level was decreased,Bax,Caspase-3,Nrf2,HO-1 levels were increased(all P<0.05);compared with Glutamate group,cell damage in TZG-L group and TZG-H group were reduced,activity of neurons was increased and apoptosis rate was decreased,Bcl-2,Nrf2,HO-1 levels were increased,Bax,Caspase-3 levels were decreased(all P<0.05).Conclusion:Tianzhi granule can inhibit neuronal apoptosis and expression of NLRP3 inflammasome in VD rats,inhibit activa-tion of microglia/astrocytes and neutrophil infiltration,improve neuroinflammation of VD,which may play a role by activating Nrf2/HO-1 signaling pathway in neurons.
5.Influence and mediation effect of adolescent obesity on myopia risk:a cross-sectional and cohort analysis based on longitudinal study of Chengdu city from 2014 to 2023
Yanqun WEN ; Ya WEN ; Kefeng LI ; Lihua DI ; Li ZHAO ; Siqi LI
Journal of China Medical University 2025;54(3):204-207
Objective To investigate the relationships between adolescents'body mass index(BMI),blood pressure(BP),and myopia and provide a scientific basis for the formulation of myopia prevention and control measures.Methods Adolescent students who par-ticipated in physical fitness surveillance in Chenghua District,Chengdu,from 2014 to 2023 were selected as the study population.A cross-sectional study was conducted using multiple logistic regression,adjusting for age,sex,BP,and pulse as covariates.A Cox model was employed to examine the relationship between obesity and myopia.Additionally,for the 2023 dataset,characterized by the largest sample size and most complete data,a mediation analysis was performed with mean BP as the mediator.Results Annual cross-sectional analysis from 2014 to 2023 revealed a significant positive association between obesity and myopia,with OR and 95%CI of 1.16(1.10-1.22),1.15(1.08-1.21),1.19(1.12-1.26),1.11(1.04-1.18),1.10(1.05-1.15),1.10(1.05-1.16),1.07(1.03-1.12),1.10(1.05-1.15),1.12(1.07-1.17),and 1.11(1.06-1.15),respectively.Similarly,cohort analysis showed a significant positive association between obesity and myopia(HR=1.09,95%CI:1.01-1.19).Mediation analysis indicated that BP accounted for 21.2%of the total effect of obesity on myopia.Conclusion Obesity facilitates the onset of myopia,and weight reduction can help decrease the likelihood of latter.Furthermore,BP mediates the impact of obesity on myopia.Implementing BP-lowering interventions in obese populations may aid in the prevention of myopia.
6.Status risk factors and prevention and control strategies of familial aggregation of Helicobacter pylori infection
Lihua SONG ; Sijing HAN ; Shuqin REN ; Wen YANG ; Sihong DING ; Yixin ZHONG ; Yao QIN ; Huiyue ZHANG ; Yang ZHANG
Journal of Public Health and Preventive Medicine 2024;35(2):148-151
Objective To investigate the status of familial aggregation of Helicobacter pylori (Hp) infection in Jinniu District, Chengdu, and analyze its risk factors so as to provide a basis for developing prevention and control strategies of family aggregation of Hp infection. Methods A total of 172 subjects in the Second Affiliated Hospital of Chengdu Medical College · 416 Hospital of Nuclear Industry from January 2022 to January 2023 were selected as the research subjects. All subjects underwent 13C-urea breath test (13C-UBT) to diagnose whether there was Hp infection. Analyze the current situation of family aggregation of Hp infection in the region, collect general data of survey subjects, analyze the relevant factors affecting Hp family aggregation infection, and develop prevention and control strategies based on this. Results A total of 242 people from 97 households were surveyed, and the Hp family aggregation rate was 29.33%. Univariate analysis showed that there were statistically significant differences in family aggregation of Hp infection in terms of different age groups (χ2=9.719, P=0.008), marital status (χ2=8.496, P=0.014), occupations (χ2=19.462, P<0.001), frequencies of dining out (χ2=5.457, P=0.019), previous Hp test results (χ2 =4.131, P=0.042) and test results after treatment (χ2=12.000, P=0.001), with statistical significance (P<0.05). Multivariate logistic regression analysis showed that the frequency of dining out 2 days or more per week and a positive Hp test results in the past were risk factors for family aggregation of Hp infection, while the occupation of teachers/medical staff/management/technology personnel and a negative Hp results after treatment were protective factors (P<0.05). Conclusion Family aggregation of Hp infection is related to family members' occupation, frequency of dining out, previous Hp test results and Hp test results after eradication, which deserves attention in clinical practice.
7.Investigation on performance of pilots in high altitude physiological training
Liping WANG ; Lihua YU ; Weiru SHI ; Yan ZHANG ; Dongqing WEN ; Guiyou WANG ; Zhao GU ; Lei TU ; Lihao XUE
Chinese Journal of Aerospace Medicine 2024;35(2):81-85
Objective:To provide basis for preventing flight safety accidents caused by hypoxia by exploring the subjective and objective performance of pilots in hypobaric hypoxia environment.Methods:The relevant data of pilots′ high altitude physiological training were retrospectively analyzed and a symptom questionnaire upon the training were summarized. The pilots were divided into excellent group (time of useful consciousness >6 min), good group (3 min ≤time of useful consciousness <6 min) and qualified group (2 min ≤time of useful consciousness <3 min) according to the time of useful consciousness. The hypoxia symptoms and physiological parameters of pilots in each group were statistically analyzed.Results:A total of 919 pilots were included, in which 416 were in excellent group, 490 were in good group and 13 were in qualified group. Among the 25 hypoxia symptoms, there were significant differences in the components of numbness and difficulty in calculation among 3 groups ( χ2=6.04, 7.79, P=0.049, 0.020), but there were no significant differences in the components of the other 23 hypoxia symptoms (all P>0.05). The changes of blood oxygen saturation were significant in group main effect, time main effect and their interaction ( F=25.65, 1 039.77, 25.22, all P<0.001). The change of heart rate was statistically significant in the main effect of time ( F=66.41, P<0.001) but in time main effect and their interaction (both P>0.05). There was no significant difference in respiratory rate among group main effect, time main effect and their interaction (all P>0.05). The distribution and variation of blood oxygen saturation were statistically significant differences among the 3 groups in the ranges of 81%-90%, 71%-80% and 65%-70% ( H=125.93, 372.83, 13.10, all P≤0.001) unlike the range of 91%-100% ( H=2.48, P=0.289). Conclusions:The excellent group showed better blood oxygen saturation maintaining and useful consciousness time enduring capabilities, and those imply them in better performance and consciousness that enable the operation in hypoxic environment with more ease.
8.Comparative analysis of 2 kinds of pilot hypoxia training effects
Yan ZHANG ; Weiru SHI ; Liping WANG ; Xiaopeng LIU ; Lihao XUE ; Dongqing WEN ; Lihua YU ; Lei TU ; Zhao GU ; Tong YANG ; Guiyou WANG
Chinese Journal of Aerospace Medicine 2024;35(2):86-90
Objective:To provide scientific basis for pilots′ hypoxia training by comparing and analyzing the effects of hypoxia training under normobaric and hypobaric environments.Methods:Forty-two healthy subjects were selected. The pilot reduced oxygen breathing device and hypobaric chamber were used to simulate 7 500 m hypoxia training, and blood oxygen saturation, heart rate, respiratory rate and hypoxia endurance time were monitored and recorded. The hypoxia symptom questionnaire was filled out by the subjects after 2 training sessions. The hypoxia endurance time and hypoxia tolerance grade of normobaric and hypobaric hypoxia training were analyzed, and the differences of blood oxygen saturation and hypoxia symptoms were compared between 2 hypoxia trainings.Results:Forty-two subjects completed the normobaric and hypobaric hypoxia trainings. The survival curve analysis of hypoxia endurance time showed that the median hypoxia endurance time of normobaric and hypobaric hypoxia training was [3.17(2.70, 3.64)] min and [3.67(3.46, 3.88)] min respectively, with no significant difference ( P>0.05). There was no significant difference in the grade distribution of hypoxia tolerance between 2 hypoxia trainings ( P>0.05). The blood oxygen saturation curves of 2 hypoxia trainings were basically consistent. There was no significant difference between 2 hypoxia trainings on blood oxygen saturation, heart rate and respiratory rate (all P>0.05). There were significant differences in difficulty in calculation, difficulty in concentration and with palpitation ( χ2=4.81, 3.97, 3.98, P=0.028, 0.046, 0.046). Conclusions:The analysis showed that most physiological responses and subjective symptoms of pilots are quite similar in the normobaric and hypobaric hypoxia training at simulated 7 500 m. Both normobaric and hypobaric exposures show the similar hypoxia training effect.
9.Efficacy evaluation of extending or switching to tenofovir amibufenamide in patients with chronic hepatitis B: a phase Ⅲ randomized controlled study
Zhihong LIU ; Qinglong JIN ; Yuexin ZHANG ; Guozhong GONG ; Guicheng WU ; Lvfeng YAO ; Xiaofeng WEN ; Zhiliang GAO ; Yan HUANG ; Daokun YANG ; Enqiang CHEN ; Qing MAO ; Shide LIN ; Jia SHANG ; Huanyu GONG ; Lihua ZHONG ; Huafa YIN ; Fengmei WANG ; Peng HU ; Xiaoqing ZHANG ; Qunjie GAO ; Chaonan JIN ; Chuan LI ; Junqi NIU ; Jinlin HOU
Chinese Journal of Hepatology 2024;32(10):883-892
Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).
10.Safety profile of tenofovir amibufenamide therapy extension or switching in patients with chronic hepatitis B: a phase Ⅲ multicenter, randomized controlled trial
Zhihong LIU ; Qinglong JIN ; Yuexin ZHANG ; Guozhong GONG ; Guicheng WU ; Lvfeng YAO ; Xiaofeng WEN ; Zhiliang GAO ; Yan HUANG ; Daokun YANG ; Enqiang CHEN ; Qing MAO ; Shide LIN ; Jia SHANG ; Huanyu GONG ; Lihua ZHONG ; Huafa YIN ; Fengmei WANG ; Peng HU ; Xiaoqing ZHANG ; Qunjie GAO ; Peng XIA ; Chuan LI ; Junqi NIU ; Jinlin HOU
Chinese Journal of Hepatology 2024;32(10):893-903
Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated.Results:666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion:CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).


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