1.Study on the progress of HIV typing methods
Qianru LIN ; Yi LIN ; Ping ZHONG ; Xin SHEN
Shanghai Journal of Preventive Medicine 2023;35(7):719-723
As a retrovirus with high recombination and mutation rate, HIV targets CD4+ T lymphocytes, causing damage to the body's immune system and eventually leading to severe immune function defects. Different subtypes of the HIV virus exhibit significant sequence differences in their structural and regulatory genes, and this diversity is closely related to etiology, transmission, diagnosis, drug therapy, disease progression, and vaccine development. As a country with the largest number of HIV subtypes, rapid and accurate typing of the HIV virus holds great significance for China's efforts in disease prevention and control. This study provides a comprehensive reveiw of domestic and international HIV genotyping methods, and summarizes the clinical significance of different subtypes in order to provide reference for further research.
2.A case report of middle ear cholesteatoma complicated with labyrinthine fistulaand delayed endolymphatic hydrops.
Feng LIN ; Qianru WU ; Yibo ZHANG ; Chunfu DAI
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2023;37(8):670-672
Delayed endolymphatic hydrops (DEH) is a rare disease that causes vertigo and is often misdiagnosed as other vertigo diseases. This article reports on a patient with vertigo who was easily misdiagnosed. The patient was a middle ear cholesteatoma complicated by labyrinthine fistula (LF); however, his vertigo was episodic vertigo, which could not be explained solely by LF causing labyrinthitis. The possibility of endolymphatic hydrops was suspected, which was confirmed by inner ear magnetic resonance gadolinium imaging. This is the first reported case of middle ear cholesteatoma complicated by LF and DEH. The patient underwent surgical resection of the cholesteatoma and three semicircular canal obstructions at the same time. During two years postoperative follow-up, the patient did not experience a recurrence of vertigo. When diagnosing vertigo diseases, a careful history of vertigo is of utmost importance.
Humans
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Endolymphatic Hydrops/diagnosis*
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Cholesteatoma, Middle Ear/complications*
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Vertigo/complications*
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Labyrinth Diseases/complications*
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Magnetic Resonance Imaging/adverse effects*
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Semicircular Canals
3.Influence of periventricular-intraventricular hemorrhage on cerebral blood flow of preterm infants in the late postnatal period observed by arterial spin labeling: a prospective study
Changyang MA ; Chen ZHANG ; Lin LU ; Meng ZHANG ; Qianru XUE ; Bin WANG ; Falin XU
Chinese Journal of Applied Clinical Pediatrics 2023;38(12):927-931
Objective:To study the influence of periventricular-intraventricular hemorrhage (PVH-IVH) on cerebral blood flow (CBF) of preterm infants in the late postnatal period using arterial spin labeling (ASL) magnetic resonance imaging (MRI).Methods:From January 2023 to June 2023, 65 preterm infants (gestational age <32 weeks, birth weight <1 500 g) who were born in the Department of Obstetrics, Third Affiliated Hospital of Zhengzhou University and transferred to the Neonatal Intensive Care Unit were included in the prospective study.They were examined by the brain MRI and ASL at the corrected gestational age of 35-40 weeks.According to the results of the brain ultrasound within 1 week after birth, they were divided into the mild IVH group (25 cases) and the non-IVH group (40 cases). The CBF values in regions of interest (frontal lobe, temporal lobe, parietal lobe, occipital lobe, thalamus, and basal ganglia) on ASL images were compared.Multiple linear regression analysis was used to analyze the effect of PVH-IVH on CBF values in different ASL regions of interest, including frontal cortex, temporal cortex, parietal cortex, occipital cortex, thalamus, and basal ganglia.Results:Compared with those of non-IVH group, infants in the mild IVH group presented significantly older gestational age [29.0 (28.5, 30.4) weeks vs.28.2 (27.0, 31.0) weeks, Z=-2.398, P=0.016], higher hematocrit (HCT) in the latest examination prior to the brain MRI [29.6(26.4, 32.3)% vs.27.8 (25.6, 30.5)%, Z=-2.155, P=0.031], and larger body weight at the time of examination [2 015.0 (1 930.0, 2 127.5) g vs.1 950.0 (1 900.0, 1 997.5) g, Z=-3.314, P=0.001]. After adjustment for confounding factors of gestational age at birth, latest HCT and weight at the time of examination, the multivariable linear regression analysis showed that CBF values in the frontal lobe (95% CI: -8.367--4.042; P<0.001), temporal lobe (95% CI: -19.077--2.854; P=0.008), parietal lobe (95% CI: -8.344--3.502; P<0.001), occipital lobe (95% CI: -9.446--3.645; P<0.001), basal ganglia (95% CI: -7.543--1.963; P=0.001) and thalamus (95% CI: -8.051--2.372; P<0.001) were significantly lower in infants of the mild IVH group than those of non-IVH group. Conclusions:At the same corrected gestational age, mild IVH is correlated with low CBF values in local cerebral cortex and subcortical gray matter in premature infants.However, the predictive potential of CBF values in long-term neurological prognosis requires further explorations.
4.Pediatric stroke with Aicardi-Goutières syndrome: a case report
Yuanyuan LI ; Mingxia LI ; Qianru YANG ; Hong LIN ; Jianjun LI ; Ying LI ; Fangfang GE
Chinese Journal of Neurology 2022;55(9):1008-1012
The clinical, imaging, genetic, therapeutic and prognostic features of a case of pediatric stroke who was finally diagnosed with Aicardi-Goutières syndrome (AGS) in Xi′an International Medical Center Hospital on October 24, 2021 were reported. A 10-year-old boy was admitted to the hospital due to weakness of the right limb for more than 10 hours. The pre-hospital CT showed multiple patchy calcifications in the bilateral frontal lobe and the right parietal lobe cortex-medullary junction. The physical examination on admission had chilblains on the hands, feet and face. National Institutes of Health Stroke Scale Score was 4 points. Brain magnetic resonance imaging showed acute brainstem infarction, no abnormality in magnetic resonance angiography, ultrasound and electrocardiogram of heart and neck vessels were normal, cerebrospinal fluid biochemistry and routine examination were normal, blood routine, biochemistry, coagulation, autoantibody series, thyroid function, tumor markers, human immunodeficiency virus and syphilis examinations were normal. After oral administration of aspirin anti-platelet aggregation and rehabilitation exercises, the muscle strength returned to normal and the patient was discharged. One month later, the result of genetic testing was reported as AGS caused by TREX1 gene mutation, and the mutation site is c.58G>A. AGS is a rare autoimmune hereditary encephalopathy with a large heterogeneity of clinical manifestations. When a hereditary disease was suspected, genetic testing should be done.
5.Predictors of long-term efficacy and recurrence of anti-vascular endothelial growth factor therapy for idiopathic choroidal neovascularization
Qianru WU ; Xiaoyong CHEN ; Kang FENG ; Yuling LIU ; Chun ZHANG ; Lin ZHAO
Chinese Journal of Ocular Fundus Diseases 2021;37(9):709-714
Objective:To investigate the clinical effects and influence factors of intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs in the treatment of idiopathic choroidal neovascularization (ICNV).Methods:This retrospective study involved 27 patients (27 eyes) with ICNV from July 2012 to July 2015. Patients received intravitreal bevacizumab (1.25 mg), ranibizumab (0.05 mg), additional injection was provided if it was needed. The average follow-up time was 168 weeks. The recovery of best corrected visual acuity (BCVA) and central foveal retinal thickness (CRT) of the affected eye was observed. Follow up once a month after the initial treatment until the lesion was completely absorbed or scarred (the first follow-up period). Follow up every 12 weeks was performed to observe the recurrence of the lesions (the second stage of long-term follow-up). One month after the last injection of the first follow-up period, according to the regression of choroidal neovascularization (CNV), the affected eyes were divided into a significant improvement group (significant improvement group) and an insignificant improvement group (non-significant improvement group)), to analyze the effects of age, course of disease, type of drugs, number of injections, baseline BCVA and CRT on the regression of CNV lesions. According to the results of long-term follow-up, the eyes were divided into recurrence group and non-recurrence group, and the factors affecting the recurrence of CNV lesions were analyzed. Measurement data between groups was compared by using independent sample t test or non-parametric test; count data was compared by using χ2 test. Logistic regression analysis was used to analyze the factors affecting the regression and recurrence of the lesion. Results:At baseline and 1 month after the last injection in the first stage, the average BCVA of the eyes were 55.70±15.21 and 73.59±12.08 letters; CRT was 338.3±89.32 and 264.5±47.47 μm, respectively. The BCVA and CRT of the affected eyes were compared at the two time points, and the differences were statistically significant ( Z= -3.886, -4.061; P<0.001). The BCVA of the eyes in the significant improvement group and the insignificant improvement group were 65.38±17.27 and 51.63±12.61 letters, respectively; the difference between the two groups of BCVA was statistically significant ( t=-2.316, P=0.029). The results of long-term follow-up showed that of the 27 eyes, 6 eyes had recurrence; the average recurrence time was 90.83±49.02 weeks. After another intravitreal injection of anti-VEGF drugs, the CNV lesions was resolved. The average injection times of the relapsed group and the non-relapsed group were 3.67±0.816 and 2.24±0.768, respectively. The average injection times of the relapsed group was significantly higher than that of the non-relapsed group, and the difference was statistically significant ( Z=-3.253, P<0.001). There was no statistically significant difference between the two groups of eyes at baseline and CRT at the last follow-up ( Z=-1.342,-1.313; P=0.195, 0.195). Conclusion:Intravitreal injection of anti-VEGF drugs can effectively increase the regression rate of BCVA and CNV lesions in ICNV eyes; high baseline visual acuity indicates better CNV lesion regression after treatment. Relapsed patients can be effectively improved after re-treatment with anti-VEGF drugs, and CNV recurrence has no significant effect on the final prognosis.
6.Experimental study of biomimetic nanoparticle probe containing hematoporphyrin monomethyl ether and its imaging and sonodynamic therapy for breast cancer
Xiaohong LIN ; Pan LI ; Qianru LI ; Ju HUANG ; Qinqin JIANG ; Li WAN ; Rui TANG ; Tao HE
Chinese Journal of Ultrasonography 2021;30(2):173-179
Objective:To develop a biomimetic nanoparticle probe of hematoporphyrin monomethyl ether (HMME) coated with breast cancer cell membrane, to observe its ability to target homologous breast cancer cells in vitro, and to investigate its effect of enhanced photoacoustic imaging and sonodynamic therapy (SDT) for breast cancer in vitro.Methods:The cell membrane of breast cancer 4T1 was extracted by chemical cleavage and repeated freezing and thawing. Then the HMME-coated polylactic acid-glycolic acid copolymer biomimetic nanoparticle was prepared by double emulsification and extrusion. The basic characteristics of nanoparticles were detected. The target ability of nanoparticles to homologous breast cancer cells and the enhancement of photoacoustic imaging were observed in vitro. Singlet oxygen sensor green (SOSG) was used to verify the reactive oxygen species (ROS) production of nanoparticles, and its SDT effect on breast cancer cells was evaluated by CCK8 cytotoxicity assay.Results:The size of the prepared CHP-NPs was uniform, the morphology was spherical "core-shell structure" , the particle size was (275.23±8.25)nm, and the surface potential was (-18.43±0.45)mV. It was observed that CHP-NPs could target homologous 4T1 cells under laser confocal microscopy. In vitro photoacoustic imaging experiments show that the photoacoustic signal of nanoparticles increases with the increase of its concentration. According to SOSG probe detection, CHP-NPs could produce ROS under ultrasonic irradiation.When CHP-NPs was incubated with 4T1 cells alone and no ultrasonic irradiation was used, the cell survival rate was not significantly affected. When the concentration was 0.6 mg/ml, the cell survival rate was still 95%. After ultrasonic irradiation, CCK8 experiment showed that the CHP-NPs had a significant SDT effect on breast cancer cells.Conclusions:The biomimetic nanomolecular probe of breast cancer cell membrane is successfully prepared. The probe has good ability to target homologous tumor, and can significantly enhance tumor photoacoustic imaging and SDT effect.
7.Analysis on characteristics of untreated 16-25 years old people living with HIV-1 at the China-Myanmar border from 2009 to 2017 based on molecular network method
Yibo DING ; Min CHEN ; Jibao WANG ; Yi FENG ; Mengze GAN ; Lijie WANG ; Qianru LIN ; Lin HE ; Yanling MA ; Mengjie HAN ; Liying MA
Chinese Journal of Experimental and Clinical Virology 2021;35(2):124-129
Objective:To analyze the epidemiological characteristics of untreated 16-25 years old people living with HIV-1 (PLWH) in Dehong on the China-Myanmar border during 2009 to 2017, by using molecular network method and to provide references for precise prevention and reduction of the spread of HIV-1 in Dehong.Methods:Screening people living with HIV-1, collecting blood sample and separating plasma, extracting RNA were performed to amplify HIV-1 pol sequence, construct molecular network by HIV-TRACE program and conduct statistical analysis. Results:Among the 573 infected persons in the group, 319 were Chinese (55.67%), 254 were Burmese (44.33%); 351 were males (61%), and 222 were females (39%); 404 had heterosexual transmission (HET, 70.51%), 110 people injected drugs (PWID, 19.20%), 51 men had sex with men (MSM, 8.9%); genotypes included 252 unique recombinant forms (43.98%), and 222 had circular recombinant forms (39.02%), 76 had HIV-1 C (13.26%) and 23 HIV-1 B (4.01%) infection. The 83 molecular networks constructed through HIV-TRACE involved 250 PLWH, 49% were the China-Myanmar mixed network (41/83). Myanmar citizens were at high risk of accessing the China-Myanmar mixed network ( AOR=2.676, p=0.002). Chinese male PWID network assortativity is 0.34, Myanmar male PWID was 0.14, MSM was 0.12. Conclusions:There is a continuous risk of cross-border transmission of HIV-1 in Dehong on the China-Myanmar border; attention should be paid to the mixed transmission of MSM and Myanmar male PWID populations with other transmission routes.
8.Study on the antibodies and viral load of HIV-1 infected individuals with different immune status
Qianru LIN ; Hejun YU ; Hui ZHANG ; Guiying LI ; Yanming SUN ; Min YANG ; Xiaomei JIN ; Liying MA ; Cong JIN ; Yao XIAO
Chinese Journal of Experimental and Clinical Virology 2021;35(2):147-151
Objective:To investigate the differences in virological and immunological indicators of HIV-1 infected individuals with different degrees of immunosuppression, analyze the correlation between the sample/cutoff ratio (S/CO), viral load (VL), Western blot (WB) band type and immune status of HIV-1 infected individuals.Methods:A total of 639 HIV-1 antibodies positive and treatment-naive samples from Henan, Beijing and Yunnan during the period of 2017-2019 were divided into three groups: no immunosuppression (CD4≥500 cells/μl), mild immunosuppressive (350cells/μl≤CD4<500cells/μl), moderate immunosuppression (200 cells/μl≤CD4<350 cells/μl), severe immunosuppression (CD4<200 cells/μl). Chi-square test was used to compare S/CO, WB band type among different immunosuppression groups, analyze the relationship between various indicators and immune status.Results:In each immunosuppressive group, S/CO>20 had the highest occurrence rate (>37%), and showed a decreasing trend with the enhancement of immunity ( P<0.05), the occurrence rate of 119%), the occurrence rate of 078%), while the occurrence rates of p55 (<40%) and p39 (<3%) were the lowest, the differences of the occurrence rates of gp41 and p51 among different immunosuppression groups were statistically significant ( P<0.05). The area under the curve determined by S/CO value combined with viral load for no, mild, moderate and severe immunosuppression groups were respectively 0.651 (95% CI: 0.600-0.702; P<0.05), 0.587 (95% CI: 0.540-0.635; P<0.05), 0.605 (95% CI: 0.560~0.650; P<0.05), 0.647 (95% CI: 0.586-0.708; P<0.05). Conclusions:The S/CO value viral load was the best for the determination of non-immunosuppressive status; The absence of gp41 and p51, S/CO>20 suggest that the patient may be in non or severe immunosuppressed state, respectively.
9.Establishment of an in vitro growth competition assay for HIV-1 CRF07_BC viral fitness
Lin HE ; Yang JIAO ; Yibo DING ; Yuanyuan ZHANG ; Qianru LIN ; Lijie WANG ; Dan LI ; Kunxue HONG ; Liying MA
Chinese Journal of Experimental and Clinical Virology 2021;35(4):457-462
Objective:To establish an in vitro growth competition assay using HIV-1 CRF07_BC infectious clone containing the mouse Thy1.1 gene or Thy1.2 gene. Methods:The mouse Thy1.1 gene and Thy1.2 gene were used to replace the 218 bases of Nef region of the CRF07_BC infectious clone (pXJDC6291-13) and construct the CRF07_BC infectious clones BCEA1 and BCEA2 plasmid. BCEA1 and BCEA2 plasmids were transfected into 293T to obtain the virus and the viral titration was measured. PM1 cells were co-infected with an equal virus. On the 3 rd to 6 th day of infection the cells were collected and labeled with specific antibodies Thy1.1 and Thy1.2. The viral fitness was detected by flow cytometry. Through "TFitness" (http: //bis.urmc.rochester.edu/vFitness) the relative viral fitness was calculated. The influence K103 N and K166R on the relative fitness of HIV-1 CRF07_BC were observed. Results:The relative fitness (1+ s) of CRF07_BC subtypes BCEA1 and BCEA2 viruses were 1.06±0.23693, which was not statistically significant. An in vitro growth competition assay for CRF07_BC was established. The in vitro growth competition assay was used to verify the relative fitness of the K103 N and K166R mutant strains to the wild strain. The relative fitness of BCEA2-K103 N/BCEA1 was 0.728282±0.16608, BCEA2-K166R/BCEA1 was 0.883385±0.19023, BCEA2-K103 N+ K166R/BCEA1 was 0.804604±0.06164. The relative fitness of K103 N resistant mutant strain and the wild strain was significantly different.Conclusions:An in vitro growth competition assay for the fitness of HIV-1 CRF07_BC virus was established. Based on the in vitro growth competition assay, the HIV-1 K103 N resistant mutant strain has reduced viral fitness.
10.Impact of TRAIL gene knockout on regulatory T cells in mice with dextran sodium sulphate-induced experimental colitis
Shijie YING ; Shuguang CAO ; Xuanping XIA ; Qianru LIN ; Yi JIANG
Chinese Journal of Microbiology and Immunology 2019;39(6):440-447
Objective To investigate the impact of knocking out tumor necrosis factor-related ap-optosis-inducing ligand ( TRAIL) gene ( TRAIL-/-) on colonic inflammation and regulatory T cells ( Treg) in mice with dextran sulfate sodium (DSS)-induced experimental colitis. Methods C57BL/6 mice were ran-domly assigned into four groups with 10 in each group:wild-type ( WT) control, WT colitis, TRAIL-/- con-trol and TRAIL-/- colitis. The mouse model of colitis was induced by oral administration of 3. 5% DSS and the severity of colonic inflammation was assessed. Peripheral blood mononuclear cells ( PBMCs) and mesen-teric lymph nodes ( MLNs) were collected. The ratios of Treg cells to CD4+T cells in PBMCs were detected by flow cytometry. Expression of Treg cell-associated transcription factor (Foxp3) and cytokine (IL-10) at mRNA level was measured by real-time fluorescent quantitative polymerase chain reaction. Western blot and enzyme-linked immunosorbent assay ( ELISA) were used to detect the expression of Foxp3 and IL-10 at pro-tein level, respectively. Results Compared with the WT control group, the WT colitis group showed signif-icantly decreased proportions of Treg cells in PBMCs [(1. 85±0. 38)% vs (3. 12±0. 69)%, P<0. 05], but increased proportions in MLNs [(11. 79±1. 18)% vs (6. 24±1. 04)%, P<0. 05]. Compared with the WT mice with colitis, the TRAIL-/- mice with colitis had more severe colonic inflammation and significantly in-creased proportions of Treg cells in PBMCs [(3. 15±0. 64)% vs (1. 85±0. 38)%, P<0. 05], but de-creased Treg cells in MLNs [(9. 80±0. 50)% vs (11. 79±1. 18)%, P<0. 05]. Expression of Foxp3 and IL-10 at mRNA and protein levels in PBMCs of the WT mice with colitis was significantly lower than that in the WT control mice [ Foxp3 mRNA: 0. 48 ± 0. 21 vs 1. 06 ± 0. 31, IL-10 mRNA: 0. 23 ± 0. 07 vs 1. 22 ± 0. 38;Foxp3 protein:0. 68±0. 12 vs 1, IL-10 protein:(4. 91± 0. 72) pg/ml vs (21. 86±2. 40) pg/ml;all P<0. 05], while in MLNs, the expression of Foxp3 and IL-10 at mRNA and protein levels was significantly higher than that of the WT control group [Foxp3 mRNA:3. 71±0. 49 vs 1. 03±0. 15, IL-10 mRNA:11. 98 ±6.10 vs 1. 01±0. 31; Foxp3 protein: 1. 60±0. 03 vs 1, IL-10 protein: (1260. 00±18. 02) pg/ml vs (1184. 00±38. 62) pg/ml;all P<0. 05]. Compared with the WT mice with colitis, the TRAIL-/-mice with colitis showed significantly increased expression of Foxp3 and IL-10 at mRNA and protein levels [ Foxp3 mRNA:1. 80±0. 49 vs 0. 48±0. 21, IL-10 mRNA:1. 67±0. 99 vs 0. 23±0. 07;Foxp3 protein:1. 10±0. 01 vs 0. 68±0. 12, IL-10 protein:(31. 33± 25. 02) pg/ml vs (4. 58±3. 73) pg/ml; all P<0. 05], while de-creased expression in MLNs [ Foxp3 mRNA: 0. 49 ± 0. 21 vs 3. 71 ± 0. 49, IL-10 mRNA: 2. 80 ± 1. 82 vs 11. 98±6. 10; Foxp3 protein: 1. 21±0. 12 vs 1. 60±0. 03, IL-10 protein: (1158. 00±26. 48) pg/ml vs (1190. 00±37. 19) pg/ml;all P<0. 05]. Conclusions Knocking out the expression of TRAIL might af-fect the ratios of Treg cells in peripheral blood and MLNs, thereby aggravating the colitis in mice.

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