1.Randomized Double-blind Placebo-controlled Study on Clinical Efficacy and Mechanism of Shexiang Baoxinwan in Treating Stable Angina Pectoris Complicated with Anxiety and Depression in Coronary Artery Disease
Jie WANG ; Linzi LONG ; Zhiru ZHAO ; Feifei LIAO ; Jieming LU ; Tianjiao LIU ; Yuxuan PENG ; Hua QU ; Changgeng FU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):159-169
ObjectiveTo evaluate the efficacy of Shexiang Baoxinwan in treating stable angina pectoris with Qi stagnation and blood stasis syndrome in patients with coronary artery disease (CAD) complicated with anxiety and depression and explore its underlying mechanisms. MethodsThis study employed a randomized, double-blind, and placebo-controlled clinical trial design. Patients admitted to the hospital were randomly assigned to the observation group and the control group, with 52 patients in each group. Patients in the observation and control groups received Shexiang Baoxinwan and placebo, respectively, both in combination with conventional Western medication. The dose was 45.0 mg, three times daily, for a total duration of eight weeks. The primary outcome was the Seattle Angina Questionnaire (SAQ) scores before and after treatment. Secondary outcomes included changes in traditional Chinese medicine (TCM) syndrome score, the patient health questionnaire-9 (PHQ-9), generalized anxiety disorder-7 (GAD-7), inflammatory markers [interleukin-18 (IL-18), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), CD40, etc.], monoamine neurotransmitters [e.g., dopamine (DA)], vascular endothelial function markers [e.g., endothelin-1(ET-1)], adipokines, and ischemia-modified albumin (IMA). Adverse reactions were also recorded. ResultsA total of 92 patients completed the study, with 44 in the observation group and 48 in the control group. Compared with baseline, both groups showed significant decreases in PHQ-9, GAD-7, and TCM syndrome scores following treatment (P<0.05), along with a significant increase in SAQ scores (P<0.05). In the observation group, DA levels were significantly increased (P<0.05), while levels of IL-18, TNF-α, CD40, ET-1, and IMA were decreased (P<0.05). In contrast, the control group exhibited significantly increased CD40 levels (P<0.05). Compared with the control group after treatment, the observation group showed significant improvements in the SAQ dimensions of physical limitation, angina stability, treatment satisfaction, and disease perception, as well as in TCM syndrome score, PHQ-9 score, IL-18, CD40, ET-1, and IMA (P<0.05). No adverse reactions were observed in either group during treatment. ConclusionShexiang Baoxinwan can improve anxiety and depression, alleviate angina symptoms, and reduce TCM symptoms of Qi stagnation and blood stasis in CAD patients. The mechanism may involve anti-inflammation, improvement of vascular endothelial function, reduction of IMA, and increase of monoamine neurotransmitter levels.
2.Randomized Double-blind Placebo-controlled Study on Clinical Efficacy and Mechanism of Shexiang Baoxinwan in Treating Stable Angina Pectoris Complicated with Anxiety and Depression in Coronary Artery Disease
Jie WANG ; Linzi LONG ; Zhiru ZHAO ; Feifei LIAO ; Jieming LU ; Tianjiao LIU ; Yuxuan PENG ; Hua QU ; Changgeng FU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):159-169
ObjectiveTo evaluate the efficacy of Shexiang Baoxinwan in treating stable angina pectoris with Qi stagnation and blood stasis syndrome in patients with coronary artery disease (CAD) complicated with anxiety and depression and explore its underlying mechanisms. MethodsThis study employed a randomized, double-blind, and placebo-controlled clinical trial design. Patients admitted to the hospital were randomly assigned to the observation group and the control group, with 52 patients in each group. Patients in the observation and control groups received Shexiang Baoxinwan and placebo, respectively, both in combination with conventional Western medication. The dose was 45.0 mg, three times daily, for a total duration of eight weeks. The primary outcome was the Seattle Angina Questionnaire (SAQ) scores before and after treatment. Secondary outcomes included changes in traditional Chinese medicine (TCM) syndrome score, the patient health questionnaire-9 (PHQ-9), generalized anxiety disorder-7 (GAD-7), inflammatory markers [interleukin-18 (IL-18), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), CD40, etc.], monoamine neurotransmitters [e.g., dopamine (DA)], vascular endothelial function markers [e.g., endothelin-1(ET-1)], adipokines, and ischemia-modified albumin (IMA). Adverse reactions were also recorded. ResultsA total of 92 patients completed the study, with 44 in the observation group and 48 in the control group. Compared with baseline, both groups showed significant decreases in PHQ-9, GAD-7, and TCM syndrome scores following treatment (P<0.05), along with a significant increase in SAQ scores (P<0.05). In the observation group, DA levels were significantly increased (P<0.05), while levels of IL-18, TNF-α, CD40, ET-1, and IMA were decreased (P<0.05). In contrast, the control group exhibited significantly increased CD40 levels (P<0.05). Compared with the control group after treatment, the observation group showed significant improvements in the SAQ dimensions of physical limitation, angina stability, treatment satisfaction, and disease perception, as well as in TCM syndrome score, PHQ-9 score, IL-18, CD40, ET-1, and IMA (P<0.05). No adverse reactions were observed in either group during treatment. ConclusionShexiang Baoxinwan can improve anxiety and depression, alleviate angina symptoms, and reduce TCM symptoms of Qi stagnation and blood stasis in CAD patients. The mechanism may involve anti-inflammation, improvement of vascular endothelial function, reduction of IMA, and increase of monoamine neurotransmitter levels.
3.Integrated multiomics reveal mechanism of Aidi Injection in attenuating doxorubicin-induced cardiotoxicity.
Yan-Li WANG ; Yu-Jie TU ; Jian-Hua ZHU ; Lin ZHENG ; Yong HUANG ; Jia SUN ; Yong-Jun LI ; Jie PAN ; Chun-Hua LIU ; Yuan LU
China Journal of Chinese Materia Medica 2025;50(8):2245-2259
The combination of Aidi Injection(ADI) and doxorubicin(DOX) is a common strategy in the treatment of cancer, which can achieve synergistic anti-tumor effects while attenuating the cardiotoxicity caused by DOX. This study aims to investigate the mechanism of ADI in attenuating DOX-induced cardiotoxicity by multi-omics. DOX was used to induce cardiotoxicity in mice, and the cardioprotective effects of ADI were evaluated based on biochemical indicators and pathological changes. Based on the results, transcriptomics, proteomics, and metabolomics were employed to analyze the changes of endogenous substances in different physiological states. Furthermore, data from multiple omics were integrated to screen key regulatory pathways by which ADI attenuated DOX-induced cardiotoxicity, and important target proteins were selected for measurement by ELISA kits and immunohistochemical analysis. The results showed that ADI significantly reduced the levels of cardiac troponin T(cTnT) and N-terminal pro-B-type natriuretic peptide(NT-proBNP) and effectively ameliorated myocardial fibrosis and intracellular vacuolization, indicating that ADI showed therapeutic effect on DOX-induced cardiotoxicity. The transcriptomics analysis screened out a total of 400 differentially expressed genes(DEGs), which were mainly enriched in inflammatory response, oxidative stress, and myocardial fibrosis. After proteomics analysis, 70 differentially expressed proteins were selected, which were mainly enriched in the inflammatory response, cardiac function, and energy metabolism. A total of 51 differentially expressed metabolites were screened by the metabolomics analysis, and they were mainly enriched in multiple signaling pathways, including the inflammatory response, lipid metabolism, and energy metabolism. The integrated data of multiple omics showed that linoleic acid metabolism, arachidonic acid metabolism, and glycerophosphate metabolism pathways played an important role in DOX-induced cardiotoxicity, and ADI may exert therapeutic effects by modulating these pathways. Target validation experiments suggested that ADI significantly regulated abnormal protein levels of cyclooxygenase-1(COX-1), cyclooxygenase-2(COX-2), prostaglandin H2(PGH2), and prostaglandin D2(PGD2) in the model group. In conclusion, ADI may attenuate DOX-induced cardiotoxicity by regulating linoleic acid metabolism, arachidonic acid metabolism, and glycerophosphate metabolism, thus alleviating inflammation of the body.
Doxorubicin/toxicity*
;
Animals
;
Mice
;
Cardiotoxicity/genetics*
;
Drugs, Chinese Herbal/administration & dosage*
;
Male
;
Proteomics
;
Metabolomics
;
Injections
;
Humans
;
Multiomics
4.Expert consensus on evaluation index system construction for new traditional Chinese medicine(TCM) from TCM clinical practice in medical institutions.
Li LIU ; Lei ZHANG ; Wei-An YUAN ; Zhong-Qi YANG ; Jun-Hua ZHANG ; Bao-He WANG ; Si-Yuan HU ; Zu-Guang YE ; Ling HAN ; Yue-Hua ZHOU ; Zi-Feng YANG ; Rui GAO ; Ming YANG ; Ting WANG ; Jie-Lai XIA ; Shi-Shan YU ; Xiao-Hui FAN ; Hua HUA ; Jia HE ; Yin LU ; Zhong WANG ; Jin-Hui DOU ; Geng LI ; Yu DONG ; Hao YU ; Li-Ping QU ; Jian-Yuan TANG
China Journal of Chinese Materia Medica 2025;50(12):3474-3482
Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards*
;
Humans
;
Consensus
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Drugs, Chinese Herbal/therapeutic use*
;
Surveys and Questionnaires
5.Mechanism of Yishen Jiangtang Decoction in regulating endoplasmic reticulum stress-mediated NLRP3 inflammasome to improve renal damage in diabetic nephropathy db/db mice.
Yun-Jie YANG ; Bin-Hua YE ; Chen QIU ; Han-Qing WU ; Bo-Wei HUANG ; Tong WANG ; Shi-Wei RUAN ; Fang GUO ; Jian-Ting WANG ; Ming-Qian JIANG
China Journal of Chinese Materia Medica 2025;50(10):2740-2749
This study aims to explore the mechanism through which Yishen Jiangtang Decoction(YSJTD) regulates endoplasmic reticulum stress(ERS)-mediated NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome to improve diabetic nephropathy(DN) in db/db mice. Thirty db/db mice were randomly divided into the model group, YSJTD group, ERS inhibitor 4-phenylbutyric acid(4-PBA) group, with 10 mice in each group. Additionally, 10 db/m mice were selected as the control group. The YSJTD group was orally administered YSJTD at a dose of 0.01 mL·g~(-1), the 4-PBA group was orally administered 4-PBA at a dose of 0.5 mg·g~(-1), and the control and model groups were given an equal volume of carboxylmethyl cellulose sodium. The treatments were administered once daily for 8 weeks. Food intake, water consumption, and body weight were recorded every 2 weeks. After the intervention, fasting blood glucose(FBG), glycosylated hemoglobin(HbA1c), urine microalbumin(U-mALB), 24-hour urine volume, serum creatinine(Scr), and blood urea nitrogen(BUN) were measured. Inflammatory markers interleukin-1β(IL-1β) and interleukin-18(IL-18) were detected using the enzyme-linked immunosorbent assay(ELISA). Renal pathology was assessed through hematoxylin-eosin(HE), periodic acid-Schiff(PAS), and Masson staining, and transmission electron microscopy(TEM). Western blot was used to detect the expression levels of glucose-regulated protein 78(GRP78), C/EBP homologous protein(CHOP), NLRP3, apoptosis-associated speck-like protein containing CARD(ASC), cysteinyl aspartate-specific proteinase(caspase-1), and gasdermin D(GSDMD) in kidney tissues. The results showed that compared to the control group, the model group exhibited poor general condition, increased weight and food and water intake, and significantly higher levels of FBG, HbA1c, U-mALB, kidney index, 24-hour urine volume, IL-1β, and IL-18. Compared to the model group, the YSJTD and 4-PBA groups showed improved general condition, increased body weight, decreased food intake, and lower levels of FBG, U-mALB, kidney index, 24-hour urine volume, and IL-1β. Specifically, the YSJTD group showed a significant reduction in IL-18 levels compared to the model group, while the 4-PBA group exhibited decreased water intake and HbA1c levels compared to the model group. Although there was a decreasing trend in water intake and HbA1c in the YSJTD group, the differences were not statistically significant. No significant differences were observed in BUN, Scr, and kidney weight among the groups. Renal pathology revealed that the model group exhibited more severe renal damage compared to the control group. Kidney sections from the model group showed diffuse mesangial proliferation in the glomeruli, tubular edema, tubular dilation, significant inflammatory cell infiltration in the interstitium, and increased glycogen staining and blue collagen deposition in the basement membrane. In contrast, the YSJTD and 4-PBA groups showed varying degrees of improvement in renal damage, glycogen staining, and collagen deposition, with the YSJTD group showing more significant improvements. TEM analysis indicated that the model group had extensive cytoplasmic edema, homogeneous thickening of the basement membrane, fewer foot processes, and widening of fused foot processes. In the YSJTD and 4-PBA groups, cytoplasmic swelling of renal tissues was reduced, the basement membrane remained intact and uniform, and foot process fusion improved.Western blot results indicated that compared to the control group, the model group showed upregulation of GRP78, CHOP, GSDMD, NLRP3, ASC, and caspase-1 expression. In contrast, both the YSJTD and 4-PBA groups showed downregulation of these markers compared to the model group. These findings suggest that YSJTD exerts a protective effect against DN by alleviating NLRP3 inflammasome activation through the inhibition of ERS, thereby improving the inflammatory response in db/db DN mice.
Animals
;
Endoplasmic Reticulum Stress/drug effects*
;
Diabetic Nephropathies/metabolism*
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NLR Family, Pyrin Domain-Containing 3 Protein/genetics*
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Drugs, Chinese Herbal/administration & dosage*
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Mice
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Inflammasomes/drug effects*
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Male
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Kidney/pathology*
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Endoplasmic Reticulum Chaperone BiP
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Humans
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Interleukin-18/genetics*
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Mice, Inbred C57BL
6.Tetrahydropalmatine acts on α7nAChR to regulate inflammation and polarization of BV2 microglia.
Yan-Jun WANG ; Guo-Liang DAI ; Pei-Yao CHEN ; Hua-Xi HANG ; Xin-Fang BIAN ; Yu-Jie CHEN ; Wen-Zheng JU
China Journal of Chinese Materia Medica 2025;50(11):3117-3126
Based on the α7 nicotinic acetylcholine receptor(α7nAChR), this study examined how tetrahydropalmatine(THP) affected BV2 microglia exposed to lipopolysaccharide(LPS), aiming to clarify the possible mechanism underlying the anti-depression effect of THP from the perspectives of preventing inflammation and regulating polarization. First, after molecular docking and determination of the content of Corydalis saxicola Bunting total alkaloids, THP was initially identified as a possible anti-depression component. The BV2 microglia model of inflammation was established with LPS. BV2 microglia were allocated into a normal group, a model group, low-and high-dose(20 and 40 μmol·L~(-1), respectively) THP groups, and a THP(20 μmol·L~(-1))+α7nAChR-specific antagonist MLA(1 μmol·L~(-1)) group. The CCK-8 assay was used to screen the safe concentration of THP. A light microscope was used to examine the morphology of the cells. Western blot and immunofluorescence were used to determine the expression of α7nAChR. qRT-PCR was performed to determine the mRNA levels of inducible nitric oxide synthase(iNOS), cluster of differentiation 86(CD86), suppressor of cytokine signaling 3(SOCS3), arginase-1(Arg-1), cluster of differentiation 206(CD206), tumor necrosis factor(TNF)-α, interleukin(IL)-6, and IL-1β. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of TNF-α, IL-6, and IL-1β in the cell supernatant. The experimental results showed that THP at concentrations of 40 μmol·L~(-1) and below had no effect on BV2 microglia. THP improved the morphology of BV2 microglia, significantly up-regulated the protein level of α7nAChR, significantly down-regulated the mRNA levels of iNOS, CD86, SOCS3, TNF-α, IL-6, and IL-1β, significantly up-regulated the mRNA levels of Arg-1 and CD206, and dramatically lowered the levels of TNF-α, IL-6, and IL-1β in the cell supernatant. However, the antagonist MLA abolished the above-mentioned ameliorative effects of THP on LPS-treated BV2 microglia. As demonstrated by the aforementioned findings, THP protected LPS-treated BV2 microglia by regulating the M1/M2 polarization and preventing inflammation, which might be connected to the regulation of α7nAChR on BV2 microglia.
Berberine Alkaloids/chemistry*
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alpha7 Nicotinic Acetylcholine Receptor/chemistry*
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Microglia/metabolism*
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Mice
;
Animals
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Cell Line
;
Corydalis/chemistry*
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Humans
;
Molecular Docking Simulation
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Inflammation/drug therapy*
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Nitric Oxide Synthase Type II/immunology*
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Tumor Necrosis Factor-alpha/immunology*
7.Current situation of medicinal animal breeding and research progress in sustainable utilization of resources.
Cheng-Cai ZHANG ; Jia WANG ; Yu-Jie ZHOU ; Xiao-Yu DAI ; Xiu-Fu WAN ; Chuan-Zhi KANG ; De-Hua WU ; Jia-Hui SUN ; Sheng WANG ; Lan-Ping GUO
China Journal of Chinese Materia Medica 2025;50(16):4397-4406
Traditional Chinese medicine(TCM) is the pillar for the development of motherland medicine, and animal medicine has a long history of application in China, characterized by wide resources, strong activity, definite efficacy, and great benefits. It has significant potential and important status in the consumption market of raw materials of TCM. In the context of global climate change, farming system alterations, and low renewability, the depletion of wild medicinal animal resources has accelerated. Accordingly, the conservation and sustainable utilization of wild resources of animal medicinal materials has become a problem that garners increasing attention and urgently needs to be solved. This paper summarizes the current situation of domestic and foreign medicinal animal breeding and research progress in industrial application in recent years and points out the issues related to standardized breeding, germplasm selection and breeding, and quality evaluation standards for medicinal animals. Furthermore, this paper discusses standardized breeding, quality standards, resource protection and utilization, and the search for alternative resources for rare and endangered medicinal animals. It proposes that researchers should systematically carry out in-depth basic research on animal medicine, improve the breeding scale and level of medicinal animals, employ modern technology to enhance the quality standards of medicinal materials, and strengthen the research and development of alternative resources. This approach aims to effectively address the relationship between protection and utilization and make a significant contribution to the sustainable development of medicinal animal resources and the animal-based Chinese medicinal material industry.
Animals
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Breeding
;
China
;
Medicine, Chinese Traditional
;
Conservation of Natural Resources
8.Dexamethasone synergizes with high-fat diet to increase lipid deposition in adipocytes
Mingli SU ; Ying WANG ; Zheng YAN ; Jia LUO ; Jie YANG ; Hua YE ; Aiming LIU ; Julin YANG
The Korean Journal of Internal Medicine 2025;40(1):92-102
Background/Aims:
Dexamethasone (DEX) is a widely used exogenous therapeutic glucocorticoid in clinical settings. Its long-term use leads to many side effects. However, its effect on metabolic disorders in individuals on a high-fat diet (HFD) remains poorly understood.
Methods:
In this study, HFD-fed mice were intraperitoneally injected with DEX 2.5 mg/kg/day for 30 days. Lipid metabolism, adipocyte proliferation, and inflammation were assayed using typical approaches.
Results:
DEX increased the epididymal fat index and epididymal adipocyte size in HFD-fed mice. The number of epididymal adipocytes with diameters > 70 μm accounted for 0.5% of the cells in the control group, 30% of the cells in the DEX group, 19% of the cells in the HFD group, and 38% of all the cells in the D+H group. Adipocyte proliferation in the D+H group was inhibited by DEX treatment. Adipocyte enlargement in the D+H group was associated with increased the lipid accumulation but not the adipocyte proliferation. In contrast, the liver triglyceride and total cholesterol levels and their metabolism were downregulated by the same treatment, indicating the therapeutic potential of DEX for nonalcoholic fatty liver disease.
Conclusions
DEX synergizes with HFD to promote lipid deposition in adipose tissues. A high risk of obesity development in patients receiving HFD and DEX treatment is suggested.
9.A novel homozygous mutation of CFAP300 identified in a Chinese patient with primary ciliary dyskinesia and infertility.
Zheng ZHOU ; Qi QI ; Wen-Hua WANG ; Jie DONG ; Juan-Juan XU ; Yu-Ming FENG ; Zhi-Chuan ZOU ; Li CHEN ; Jin-Zhao MA ; Bing YAO
Asian Journal of Andrology 2025;27(1):113-119
Primary ciliary dyskinesia (PCD) is a clinically rare, genetically and phenotypically heterogeneous condition characterized by chronic respiratory tract infections, male infertility, tympanitis, and laterality abnormalities. PCD is typically resulted from variants in genes encoding assembly or structural proteins that are indispensable for the movement of motile cilia. Here, we identified a novel nonsense mutation, c.466G>T, in cilia- and flagella-associated protein 300 ( CFAP300 ) resulting in a stop codon (p.Glu156*) through whole-exome sequencing (WES). The proband had a PCD phenotype with laterality defects and immotile sperm flagella displaying a combined loss of the inner dynein arm (IDA) and outer dynein arm (ODA). Bioinformatic programs predicted that the mutation is deleterious. Successful pregnancy was achieved through intracytoplasmic sperm injection (ICSI). Our results expand the spectrum of CFAP300 variants in PCD and provide reproductive guidance for infertile couples suffering from PCD caused by them.
Adult
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Female
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Humans
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Male
;
Pregnancy
;
China
;
Ciliary Motility Disorders/genetics*
;
Codon, Nonsense
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East Asian People/genetics*
;
Exome Sequencing
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Homozygote
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Infertility, Male/genetics*
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Kartagener Syndrome/genetics*
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Pedigree
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Sperm Injections, Intracytoplasmic
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Cytoskeletal Proteins/genetics*
10.Epidemiological characteristics of respiratory syncytial virus infection in children in Hebei Province.
Xuan WANG ; Su-Kun LU ; Jian-Hua LIU ; Jin-Feng SHUAI ; Kun-Ling HUANG ; Bo NIU ; Li-Jie CAO ; Xiao-Wei CUI
Chinese Journal of Contemporary Pediatrics 2025;27(10):1199-1204
OBJECTIVES:
To study the epidemiological characteristics of respiratory syncytial virus (RSV) infection in hospitalized children with community-acquired pneumonia (CAP) in Hebei Province.
METHODS:
Hospitalized children with CAP who tested positive for RSV and were admitted to Hebei Children's Hospital from various cities and counties across Hebei Province between January 2019 and December 2023 were included in the study. Clinical data were collected and analyzed to assess epidemiological characteristics.
RESULTS:
The clinical data of 43 978 children with CAP were collected, with an overall RSV detection rate of 25.98%. The detection rate was higher during the implementation of non-pharmaceutical interventions (NPIs) (30.60%) than in the non-NPIs period. Winter and spring were the primary epidemic seasons for RSV each year except in 2022. The detection rate in males (26.62%) was higher than in females (25.06%) (P<0.001). The highest detection rate (59.18%) was found in infants aged 29 days to <1 year. Single RSV infection was more common, with rhinovirus being the most frequent co-infection.
CONCLUSIONS
The overall RSV detection rate in Hebei Province is influenced by NPIs, being higher during their implementation. RSV predominantly circulates in winter and spring. The detection rate of RSV is higher in males and infants. RSV infection is primarily single, most often co-occurring with rhinovirus.
Humans
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Respiratory Syncytial Virus Infections/epidemiology*
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Female
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Male
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Infant
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Child, Preschool
;
Seasons
;
China/epidemiology*
;
Infant, Newborn
;
Community-Acquired Infections/epidemiology*
;
Child

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