2.Clinical characteristics and risk factors of human cytomegalovirus infection in pediatric patients after allogeneic hematopoietic stem cell transplantation
Yuting HU ; Guangyu XUE ; Shunqiao FENG ; Qin LUO ; Yingli QU ; Jin CAO ; Wenyan TIAN ; Feng HE ; Haijun DU ; Chen GAO ; Qinqin SONG ; Hailan YAO ; Jun HAN
Chinese Journal of Experimental and Clinical Virology 2025;39(3):345-352
Objective:To analyze the risk factors for human cytomegalovirus (HCMV) infection in pediatric recipients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:Clinical data of children who underwent first allo-HSCT were retrospectively analyzed from March 2017 to November 2024. A total of 259 pediatric allo-HSCT recipients were analyzed through comparing HCMV infection group (n=115) and Non-HCMV infection group (n=144). Clinical characteristics were compared, and risk factors for HCMV infection were analyzed using univariate and multivariate logistic regression.Results:The result of univariate analysis showed that adrenoleukodystrophy (ALD), length of hospitalization, duration of antiviral therapy, and bacterial infection were significantly associated with HCMV infection in pediatric allo-HSCT recipients ( P<0.05). The result of multivariate analysis showed that ALD was an independent protective factor against HCMV infection of allo-HSCT recipients ( P<0.05) [OR=0.22, 95% CI: 0.06-0.86], while umbilical cord blood transplantation (UCBT) was an independent risk factor for HCMV infection in allo-HSCT recipients ( P<0.05) [OR=6.13, 95% CI: 1.34-28.04]. When the area under the ROC curve (AUC) for predicting post-transplant relapse based on HCMV viral load was 0.75 (95% CI: 0.55-0.94, P=0.014) and at the cutoff value of 3×10 3 copies/ml, the sensitivity and specificity for predicting relapse were 81.13% and 66.67%, respectively. Conclusions:HCMV infection in pediatric allo-HSCT recipients may lead to longer hospitalization and increased risk of relapse.
3.Differences in cytokines expression between mild and severe infant cases infected with respiratory syncytial virus
Guangyu XUE ; Yuting HU ; Kexin ZONG ; Qin LUO ; Shengnan YANG ; Miao FENG ; Xiaoyu YI ; Zhiqiang XIA ; Chen GAO ; Haijun DU ; Ying LI ; Ying CHEN ; Feng HE ; Yajuan WANG ; Yingli QU ; Jin CAO ; Wenyan TIAN ; Qinqin SONG ; Hailan YAO ; Jun HAN
Chinese Journal of Experimental and Clinical Virology 2025;39(3):370-377
Objective:To analyze the clinical characteristics and cytokines expression characteristics in infants with mild and severe respiratory syncytial virus (RSV) infection.Methods:From May 2023 to December 2023, plasma samples and clinical information were collected from 16 infants with RSV infection and 14 control infants. Cytek Aurora flow cytometry (Cytek, America) and Enzyme linked immunosorbent assay (ELISA) were used to detect the expression levels of 25 cytokines after mild and severe RSV infection.Results:Cough and nasal obstruction were the main clinical manifestations in infants with mild RSV infection, accompanied by polypnea, wheezing and other symptoms. The main symptoms of severe RSV infection were cough and rales, accompanied by fever and polypnea. In comparison with the control group, the expression levels of IL-2, IL-4, IL-5, IL-6, IL-9, IL-13, IL-22, TNF-α, IFN-α, IFN-β, MIP-1β, I-TAC, ENA-78, GROα, Eotaxin, and MCP-1 in the RSV infection group all exhibited an upregulation trend. Both IP-10 and MIP-3α demonstrated a downward trend in the RSV infection group; however, there was no statistically significant difference ( P>0.05). The levels of IL-10, IFN-γ, MIP-1α, and IL-8 in the RSV infection group were significantly higher than those in the control group, whereas the levels of MIG, TARC, and RANTES in the RSV infection group were significantly lower than those in the control group ( P<0.05). The levels of IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-22, IFN-β, IFN-γ, TNF-α, IL-8, I-TAC, MIP-1β, Eotaxin, and MCP-1 in the mild RSV infection group were significantly higher than those in the severe RSV infection group ( P>0.05). Among these, the levels of MIG, RANTES, TARC, MIP-3α, and ENA-78 in the mild infection group were all lower than those in the severe infection group. The expressions of ENA-78 and MIP-1α in the severe infection group were significantly higher than those in the mild infection group and also higher than those in the control group. There was no significant difference in IP-10 and GROα between the mild and severe RSV infection groups ( P>0.05). Conclusions:The differences in clinical features and cytokines between infants with mild and severe RSV infection provide important data support for the prevention and treatment of RSV infection in infants.
4.Clinical characteristics and risk factors of human cytomegalovirus infection in pediatric patients after allogeneic hematopoietic stem cell transplantation
Yuting HU ; Guangyu XUE ; Shunqiao FENG ; Qin LUO ; Yingli QU ; Jin CAO ; Wenyan TIAN ; Feng HE ; Haijun DU ; Chen GAO ; Qinqin SONG ; Hailan YAO ; Jun HAN
Chinese Journal of Experimental and Clinical Virology 2025;39(3):345-352
Objective:To analyze the risk factors for human cytomegalovirus (HCMV) infection in pediatric recipients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:Clinical data of children who underwent first allo-HSCT were retrospectively analyzed from March 2017 to November 2024. A total of 259 pediatric allo-HSCT recipients were analyzed through comparing HCMV infection group (n=115) and Non-HCMV infection group (n=144). Clinical characteristics were compared, and risk factors for HCMV infection were analyzed using univariate and multivariate logistic regression.Results:The result of univariate analysis showed that adrenoleukodystrophy (ALD), length of hospitalization, duration of antiviral therapy, and bacterial infection were significantly associated with HCMV infection in pediatric allo-HSCT recipients ( P<0.05). The result of multivariate analysis showed that ALD was an independent protective factor against HCMV infection of allo-HSCT recipients ( P<0.05) [OR=0.22, 95% CI: 0.06-0.86], while umbilical cord blood transplantation (UCBT) was an independent risk factor for HCMV infection in allo-HSCT recipients ( P<0.05) [OR=6.13, 95% CI: 1.34-28.04]. When the area under the ROC curve (AUC) for predicting post-transplant relapse based on HCMV viral load was 0.75 (95% CI: 0.55-0.94, P=0.014) and at the cutoff value of 3×10 3 copies/ml, the sensitivity and specificity for predicting relapse were 81.13% and 66.67%, respectively. Conclusions:HCMV infection in pediatric allo-HSCT recipients may lead to longer hospitalization and increased risk of relapse.
5.Differences in cytokines expression between mild and severe infant cases infected with respiratory syncytial virus
Guangyu XUE ; Yuting HU ; Kexin ZONG ; Qin LUO ; Shengnan YANG ; Miao FENG ; Xiaoyu YI ; Zhiqiang XIA ; Chen GAO ; Haijun DU ; Ying LI ; Ying CHEN ; Feng HE ; Yajuan WANG ; Yingli QU ; Jin CAO ; Wenyan TIAN ; Qinqin SONG ; Hailan YAO ; Jun HAN
Chinese Journal of Experimental and Clinical Virology 2025;39(3):370-377
Objective:To analyze the clinical characteristics and cytokines expression characteristics in infants with mild and severe respiratory syncytial virus (RSV) infection.Methods:From May 2023 to December 2023, plasma samples and clinical information were collected from 16 infants with RSV infection and 14 control infants. Cytek Aurora flow cytometry (Cytek, America) and Enzyme linked immunosorbent assay (ELISA) were used to detect the expression levels of 25 cytokines after mild and severe RSV infection.Results:Cough and nasal obstruction were the main clinical manifestations in infants with mild RSV infection, accompanied by polypnea, wheezing and other symptoms. The main symptoms of severe RSV infection were cough and rales, accompanied by fever and polypnea. In comparison with the control group, the expression levels of IL-2, IL-4, IL-5, IL-6, IL-9, IL-13, IL-22, TNF-α, IFN-α, IFN-β, MIP-1β, I-TAC, ENA-78, GROα, Eotaxin, and MCP-1 in the RSV infection group all exhibited an upregulation trend. Both IP-10 and MIP-3α demonstrated a downward trend in the RSV infection group; however, there was no statistically significant difference ( P>0.05). The levels of IL-10, IFN-γ, MIP-1α, and IL-8 in the RSV infection group were significantly higher than those in the control group, whereas the levels of MIG, TARC, and RANTES in the RSV infection group were significantly lower than those in the control group ( P<0.05). The levels of IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-22, IFN-β, IFN-γ, TNF-α, IL-8, I-TAC, MIP-1β, Eotaxin, and MCP-1 in the mild RSV infection group were significantly higher than those in the severe RSV infection group ( P>0.05). Among these, the levels of MIG, RANTES, TARC, MIP-3α, and ENA-78 in the mild infection group were all lower than those in the severe infection group. The expressions of ENA-78 and MIP-1α in the severe infection group were significantly higher than those in the mild infection group and also higher than those in the control group. There was no significant difference in IP-10 and GROα between the mild and severe RSV infection groups ( P>0.05). Conclusions:The differences in clinical features and cytokines between infants with mild and severe RSV infection provide important data support for the prevention and treatment of RSV infection in infants.
6.Establishment of ultra-performance liquid chromatography-tandem mass spectrometry method for assay of tobramycin in human serum and its use in a pharmacokinetic study of tobramycin inhalation in bronchiectasis patients
Yu WANG ; Xiaoyong XU ; Xiaolan HUANG ; Xiaofen LIU ; Yaxin FAN ; Jiali HU ; Hailan WU ; Jing ZHANG ; Beining GUO
Chinese Journal of Infection and Chemotherapy 2024;24(5):545-552
Objective To establish an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method for determination of tobramycin in human serum,and examine the utility of the method in a clinical pharmacokinetic study of tobramycin inhalation.Methods Serum samples were pretreated by solid phase extraction with tobramycin-D12 as internal standard.Chromatographic separation was performed on a TitankHilic(2.1 mm × 100 mm,3 μm)column.The mobile phase consisted of0.1%formic acid-acetonitrile and 0.1%formic acid aqueous solution at a flow rate of 0.4 mL/min.Electrospray ionization source and multiple reaction monitoring(MRM)scanning were used for monitoring the quantitative ion pairs with m/z 468.3→m/z 163.3(tobramycin)and m/z 480.6→m/z 166.2(tobramycin-D12).The established method was investigated in terms of selectivity,interaction,concomitant medication,standard curve and lower limit of quantitation,precision and accuracy,recovery,matrix effect,and stability of tobramycinin.Results The linear range of tobramycin was 0.050 0-10.0 mg/L(R2=0.999 5).The intra-and inter-batch precision was satisfactory(coefficient of variation[CV]≤3.6%).The accuracy ranged from-0.4%to 6.0%.The matrix effect factor(MF)in human serum samples(including hemolysis and lipemia)ranged from 92.2%to 94.9%(CV≤2.7%).The recovery of tobramycinin was 79.5%-81.9%in serum samples,while the recovery of internal standard was 78.9%.The analyte was stable in serum samples for 72 h at room temperature and for 274 days at-20℃/-70℃.The pharmacokinetic study of tobramycin inhalation in bronchiectasis patients showed that after continuous administration of tobramycin 300 mg twice a day to 3 patients,the mean Cmax of tobramycin was(0.72±0.61)mg/L on Day 1 and(0.76±0.73)mg/L on Day 28,respectively.The corresponding Tmax was(1.83±0.61)h and(1.50±0.50)h,respectively.Conclusions The UPLC-MS/MS method established in this study is sensitive,accurate and rapid.It is successfully applied to the clinical pharmacokinetic study of tobramycin inhalation.The method may be suitable for therapeutic drug monitoring of tobramycin in clinical practice.
7.A Wnt10a-Notch signaling axis controls Hertwig's epithelial root sheath cell behaviors during root furcation patterning
Sun KAI ; Yu MIAO ; Wang JIAYU ; Zhao HU ; Liu HAOCHEN ; Feng HAILAN ; Liu YANG ; Han DONG
International Journal of Oral Science 2024;16(3):425-435
Human with bi-allelic WNT10A mutations and epithelial Wnt10a knockout mice present enlarged pulp chamber and apical displacement of the root furcation of multi-rooted teeth,known as taurodontism;thus,indicating the critical role of Wnt10a in tooth root morphogenesis.However,the endogenous mechanism by which epithelial Wnt10a regulates Hertwig's epithelial root sheath(HERS)cellular behaviors and contributes to root furcation patterning remains unclear.In this study,we found that HERS in the presumptive root furcating region failed to elongate at an appropriate horizontal level in K14-Cre;Wnt10afl/flmice from post-natal day 0.5(PN0.5)to PN4.5.EdU assays and immunofluorescent staining of cyclin D1 revealed significantly decreased proliferation activity of inner enamel epithelial(IEE)cells of HERS in K14-Cre;Wnt10afl/flmice at PN2.5 and PN3.5.Immunofluorescent staining of E-Cadherin and acetyl-α-Tubulin demonstrated that the IEE cells of HERS tended to divide perpendicularly to the horizontal plane,which impaired the horizontal extension of HERS in the presumptive root furcating region of K14-Cre;Wnt10afl/flmice.RNA-seq and immunofluorescence showed that the expressions of Jag1 and Notch2 were downregulated in IEE cells of HERS in K14-Cre;Wnt10afl/fl mice.Furthermore,after activation of Notch signaling in K14-Cre;Wnt10afl/flmolars by Notch2 adenovirus and kidney capsule grafts,the root furcation defect was partially rescued.Taken together,our study demonstrates that an epithelial Wnt10a-Notch signaling axis is crucial for modulating HERS cell proper proliferation and horizontal-oriented division during tooth root furcation morphogenesis.
8.A Critical Role for γCaMKII in Decoding NMDA Signaling to Regulate AMPA Receptors in Putative Inhibitory Interneurons.
Xingzhi HE ; Yang WANG ; Guangjun ZHOU ; Jing YANG ; Jiarui LI ; Tao LI ; Hailan HU ; Huan MA
Neuroscience Bulletin 2022;38(8):916-926
CaMKII is essential for long-term potentiation (LTP), a process in which synaptic strength is increased following the acquisition of information. Among the four CaMKII isoforms, γCaMKII is the one that mediates the LTP of excitatory synapses onto inhibitory interneurons (LTPE→I). However, the molecular mechanism underlying how γCaMKII mediates LTPE→I remains unclear. Here, we show that γCaMKII is highly enriched in cultured hippocampal inhibitory interneurons and opts to be activated by higher stimulating frequencies in the 10-30 Hz range. Following stimulation, γCaMKII is translocated to the synapse and becomes co-localized with the postsynaptic protein PSD-95. Knocking down γCaMKII prevents the chemical LTP-induced phosphorylation and trafficking of AMPA receptors (AMPARs) in putative inhibitory interneurons, which are restored by overexpression of γCaMKII but not its kinase-dead form. Taken together, these data suggest that γCaMKII decodes NMDAR-mediated signaling and in turn regulates AMPARs for expressing LTP in inhibitory interneurons.
Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism*
;
Hippocampus/metabolism*
;
Interneurons/physiology*
;
Long-Term Potentiation/physiology*
;
N-Methylaspartate/metabolism*
;
Receptors, AMPA/physiology*
;
Receptors, N-Methyl-D-Aspartate/metabolism*
;
Synapses/physiology*
9.Characteristics and trends of induced abortions: a retrospective study in Xiamen from 2014 to 2018
Zhenyu LUO ; Wenrong WANG ; Dongning CHAI ; Ruide SU ; Lingling ZHUANG ; Yupin SHEN ; Meiying HU ; Hailan SHEN ; Yingyin CAI
Chinese Journal of Reproduction and Contraception 2020;40(6):490-495
Objective:To investigate the characteristics and trends of women who underwent induced abortion in recent years, and to provide more evidences to decrease induced abortion rate.Methods:A retrospective study was conducted on women who underwent induced abortions in the Family Planning Department of Women and Children’s Hospital of Xiamen University from January 2014 to December 2018.Results:Of the 28 529 women with induced abortion, the age was (28.77±5.78) years old. Women aged 25-34 years accounted for 58.1%, 67.0% of women were married, 62.5% had a history of delivery, 24.0% were in their first pregnancies, 30.3% had induced abortion for twice, 21.5% were for three times and more (the maximum frequency of induced abortion was 14). About 16.1% induced abortion women had a history of cesarean section,and rate showed an increasing trend in the five years (16.2%, 15.0%, 15.9%, 16.6%, 16.9%), but the difference was not statistically significant ( P=0.054). From 2014 to 2018, the age of induced abortion women [(28.05±5.69) years, (28.47±5.62) years, (28.70±5.80) years, (29.03±5.81) years, (29.59±5.82) years, P<0.001] and the percentages of married women (63.2%, 66.8%, 66.9%, 67.2%, 70.9%), women with two or more children (11.8%, 15.4%, 20.2%, 25.2%, 32.2%) and women undergoing at least a second abortion over 35 years old (21.7%, 22.1%, 23.4%, 26.7%, 29.9%) increased every year (all P<0.001). However, among the induced abortion women, the percentages of unmarried women (36.8%, 33.2%, 33.1%, 32.8%, 29.1%), women who haven’t bear children (42.9%, 38.4%, 37.8%, 36.3%, 32.4%), women with the first pregnancy (26.2%, 23.8%, 24.7%, 23.4%, 21.8%) and women under 24 years old (29.3%, 25.3%, 24.7%, 24.1%, 21.5%) decreased during the five years period (all P<0.001). Conclusion:The incidence rate of induced abortion among married women with children is the highest, so special attention should be paid to postpartum women in family planning services, and it is urgent to launch postpartum contraceptive services and promote long-term reversible contraceptive measures.
10.Characteristics and trends of induced abortions: a retrospective study in Xiamen from 2014 to 2018
Zhenyu LUO ; Wenrong WANG ; Dongning CHAI ; Ruide SU ; Lingling ZHUANG ; Yupin SHEN ; Meiying HU ; Hailan SHEN ; Yingyin CAI
Chinese Journal of Reproduction and Contraception 2020;40(6):490-495
Objective:To investigate the characteristics and trends of women who underwent induced abortion in recent years, and to provide more evidences to decrease induced abortion rate.Methods:A retrospective study was conducted on women who underwent induced abortions in the Family Planning Department of Women and Children’s Hospital of Xiamen University from January 2014 to December 2018.Results:Of the 28 529 women with induced abortion, the age was (28.77±5.78) years old. Women aged 25-34 years accounted for 58.1%, 67.0% of women were married, 62.5% had a history of delivery, 24.0% were in their first pregnancies, 30.3% had induced abortion for twice, 21.5% were for three times and more (the maximum frequency of induced abortion was 14). About 16.1% induced abortion women had a history of cesarean section,and rate showed an increasing trend in the five years (16.2%, 15.0%, 15.9%, 16.6%, 16.9%), but the difference was not statistically significant ( P=0.054). From 2014 to 2018, the age of induced abortion women [(28.05±5.69) years, (28.47±5.62) years, (28.70±5.80) years, (29.03±5.81) years, (29.59±5.82) years, P<0.001] and the percentages of married women (63.2%, 66.8%, 66.9%, 67.2%, 70.9%), women with two or more children (11.8%, 15.4%, 20.2%, 25.2%, 32.2%) and women undergoing at least a second abortion over 35 years old (21.7%, 22.1%, 23.4%, 26.7%, 29.9%) increased every year (all P<0.001). However, among the induced abortion women, the percentages of unmarried women (36.8%, 33.2%, 33.1%, 32.8%, 29.1%), women who haven’t bear children (42.9%, 38.4%, 37.8%, 36.3%, 32.4%), women with the first pregnancy (26.2%, 23.8%, 24.7%, 23.4%, 21.8%) and women under 24 years old (29.3%, 25.3%, 24.7%, 24.1%, 21.5%) decreased during the five years period (all P<0.001). Conclusion:The incidence rate of induced abortion among married women with children is the highest, so special attention should be paid to postpartum women in family planning services, and it is urgent to launch postpartum contraceptive services and promote long-term reversible contraceptive measures.

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