1.Network pharmacology and animal experiments reveal molecular mechanisms of Cordyceps sinensis in ameliorating heart aging and injury in mice by regulating Nrf2/HO-1/NF-κB pathway.
Si-Yi LIU ; Yue TU ; Wei-Ming HE ; Wen-Jie LIU ; Kai-Zhi WEN ; Cheng-Juan LI ; Chao HAN ; Xin-Yu LIANG
China Journal of Chinese Materia Medica 2025;50(4):1063-1074
This study aims to explore the effects and mechanisms of the traditional Chinese medicine Cordyceps sinensis(CS) in ameliorating heart aging and injury in mice based on animal experiments and network pharmacology. A mouse model of heart aging was established by continuously subcutaneous injection of D-galactose(D-gal). Thirty mice were randomly assigned into a normal group, a model group, a low-dose CS(CS-L) group, a high-dose CS(CS-H) group, and a vitamin E(VE) group. Mice in these groups were administrated with normal saline, different doses of CS suspension, or VE suspension via gavage daily. After 60 days of treatment with D-gal and various drugs, all mice were euthanized, and blood and heart tissue samples were collected for determination of the indicators related to heart aging and injury in mice. Experimental results showed that both high and low doses of CS and VE ameliorated the aging phenotype, improved the heart index and myocardial enzyme spectrum, restored the expression levels of proteins associated with cell cycle arrest and senescence-associated secretory phenotypes(SASP), and alleviated the fibrosis and histopathological changes of the heart tissue in model mice. From the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),259 active ingredients of CS were retrieved. From Gene Cards and OMIM, 2 568 targets related to heart aging were identified, and 133common targets shared by CS and heart aging were obtained. The Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes( KEGG) pathway enrichment revealed that the pathways related to heart aging involved oxidative stress,apoptosis, inflammation-related signaling pathways, etc. The animal experiment results showed that both high and low doses of CS and VE ameliorated oxidative stress and apoptosis in the heart tissue to varying degrees in model mice. Additionally, CS-H and VE activated the nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1) pathway and inhibited the expression of key proteins in the nuclear factor-κB(NF-κB) pathway in the heart tissue of model mice. In conclusion, this study demonstrated based on network pharmacology and animal experiments that CS may alleviate heart aging and injury in aging mice by reducing oxidative stress,apoptosis, and inflammation in the heart via the Nrf2/HO-1/NF-κB pathway.
Animals
;
Cordyceps/chemistry*
;
Mice
;
NF-E2-Related Factor 2/genetics*
;
NF-kappa B/genetics*
;
Aging/genetics*
;
Male
;
Signal Transduction/drug effects*
;
Network Pharmacology
;
Drugs, Chinese Herbal/pharmacology*
;
Heme Oxygenase-1/genetics*
;
Heart/drug effects*
;
Humans
;
Myocardium/metabolism*
;
Membrane Proteins/genetics*
2.Dahuang Zhechong Pills delay heart aging by reducing cardiomyocyte apoptosis via PI3K/AKT/HIF-1α signaling pathway.
Wen-Jie LIU ; Yue TU ; Wei-Ming HE ; Si-Yi LIU ; Liu-Yun-Xin PAN ; Kai-Zhi WEN ; Cheng-Juan LI ; Chao HAN
China Journal of Chinese Materia Medica 2025;50(5):1276-1285
This study aimed to investigate the effect of Dahuang Zhechong Pills(DHZCP) in delaying heart aging(HA) and explore the potential mechanism. Network pharmacology and molecular docking were employed to explore the targets and potential mechanisms of DHZCP in delaying HA. Furthermore, in vitro experiments were conducted with the DHZCP-containing serum to verify key targets and pathways in D-galactose(D-gal)-induced aging of cardiomyocytes. Active components of DHZCP were searched against the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCSMP), and relevant targets were predicted. HA-related targets were screened from the GeneCards, Online Mendelian Inheritance in Man(OMIM), and DisGeNET. The common targets shared by the active components of DHZCP and HA were used to construct a protein-protein interaction network in STRING 12.0, and core targets were screened based on degree in Cytoscape 3.9.1. Metaspace was used for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses of the core targets to predict the mechanisms. Molecular docking was performed in AutoDock Vina. The results indicated that a total of 774 targets of the active components of DHZCP and 4 520 targets related to HA were screened out, including 510 common targets. Core targets included B-cell lymphoma 2(BCL-2), serine/threonine kinase 1(AKT1), and hypoxia-inducible factor 1 subunit A(HIF1A). The GO and KEGG enrichment analyses suggested that DHZCP mainly exerted its effects via the phosphatidylinositol 3-kinase(PI3K)/AKT signaling pathway, HIF-1α signaling pathway, longevity signaling pathway, and apoptosis signaling pathway. Among the pathways predicted by GO and KEGG enrichment analyses, the PI3K/AKT/HIF-1α signaling pathway was selected for verification. The cell-counting kit 8(CCK-8) assay showed that D-gal significantly inhibited the proliferation of H9c2 cells, while DHZCP-containing serum increased the viability of H9c2 cells. SA-β-gal staining revealed a significant increase in the number of blue-green positive cells in the D-gal group, which was reduced by DHZCP-containing serum. TUNEL staining showed that DHZCP-containing serum decreased the number of apoptotic cells. After treatment with DHZCP-containing serum, the protein levels of Klotho, BCL-2, p-PI3K/PI3K, p-AKT1/AKT1, and HIF-1α were up-regulated, while those of P21, P16, BCL-2 associated X protein(Bax), and cleaved caspase-3 were down-regulated. The results indicated that DHZCP delayed HA via multiple components, targets, and pathways. Specifically, DHZCP may delay HA by reducing apoptosis via activating the PI3K/AKT/HIF-1α signaling pathway.
Proto-Oncogene Proteins c-akt/genetics*
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Drugs, Chinese Herbal/pharmacology*
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Signal Transduction/drug effects*
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Apoptosis/drug effects*
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Myocytes, Cardiac/cytology*
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Hypoxia-Inducible Factor 1, alpha Subunit/genetics*
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Phosphatidylinositol 3-Kinases/genetics*
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Animals
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Rats
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Humans
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Molecular Docking Simulation
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Aging/metabolism*
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Protein Interaction Maps/drug effects*
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Heart/drug effects*
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Network Pharmacology
3.Randomized, double-blind, parallel-controlled, multicenter, equivalence clinical trial of Jiuwei Xifeng Granules(Os Draconis replaced by Ostreae Concha) for treating tic disorder in children.
Qiu-Han CAI ; Cheng-Liang ZHONG ; Si-Yuan HU ; Xin-Min LI ; Zhi-Chun XU ; Hui CHEN ; Ying HUA ; Jun-Hong WANG ; Ji-Hong TANG ; Bing-Xiang MA ; Xiu-Xia WANG ; Ai-Zhen WANG ; Meng-Qing WANG ; Wei ZHANG ; Chun WANG ; Yi-Qun TENG ; Yi-Hui SHAN ; Sheng-Xuan GUO
China Journal of Chinese Materia Medica 2025;50(6):1699-1705
Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent
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Child
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Child, Preschool
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Female
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Humans
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Male
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Double-Blind Method
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Drugs, Chinese Herbal/therapeutic use*
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Tic Disorders/drug therapy*
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Treatment Outcome
4.Qualitative and quantitative analysis of chemical components of different processed products of Corni Fructus by UPLC-Q-TOF-MS and UPLC-QqQ-MS/MS.
Li-Qiang ZHANG ; Guo-Shun SHAN ; Yi-Dan HONG ; Si-Han LIU ; Guo-Wei XU ; Hui GAO ; Wei WANG ; Cheng-Guo JU
China Journal of Chinese Materia Medica 2025;50(8):2145-2158
Qualitative and quantitative analysis methods for chemical components of different processed products of Corni Fructus were established to systematically characterize and identify these components, and the content of the main differential components was determined. The chemical components of different processed products of Corni Fructus were collected using ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS). Through analysis of self-built databases, literature, and reference standards, a total of 93 components were obtained, including 19 iridoids, 15 flavonoids, 16 organic acids, eight triterpenoids, eight tannins, four amino acids, two polysaccharides, five olefins, and 16 other compounds. Additionally, by using multivariate statistical methods, the differential components between different processed products of Corni Fructus were screened under the conditions of VIP>1.0 and FC<0.5 or FC>2.0 and P<0.05. The PCA and OPLS-DA results showed differences in the chemical components between different processed products of Corni Fructus. A total of 21 differential components were screened, including tartaric acid, morroniside, and rutin. On this basis, ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry(UPLC-QqQ-MS/MS) was used to determine the content of 10 main common differential components, including gallic acid, morroniside, ursolic acid, loganin, swertiamarin, rutin, 5-hydroxymethylfurfural, cornuside Ⅰ, quercetin, and oleanolic acid. The above 10 components showed a good linear relationship within the determined concentration range, with the precision, stability, repeatability, and sample recovery rate all meeting the requirements. Compared with that in Corni Fructus, the content of iridoid glycosides in wine-prepared Corni Fructus and wine-and honey-prepared Corni Fructus decreased, while the content of gallic acid, rutin, quercetin, 5-hydroxymethylfurfural, ursolic acid, and oleanolic acid increased. Compared with wine-prepared Corni Fructus, wine-and honey-prepared Corni Fructus showed varying degrees of increase in all other components, except for a slight decrease in gallic acid content. In summary, this study clarified the influence of different processing methods on the chemical components of Corni Fructus, providing a theoretical basis for the scientific connotation, overall quality evaluation, and clinically rational application of Corni Fructus processing in the future.
Tandem Mass Spectrometry/methods*
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Chromatography, High Pressure Liquid/methods*
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Cornus/chemistry*
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Drugs, Chinese Herbal/chemistry*
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Fruit/chemistry*
5.Integrating traditional Chinese medicine constitutions into insomnia management: Findings from a cross-sectional study.
Yan HAN ; Yu WANG ; Mo-Yi SHI ; Yu LIU ; Xiao-Dong CHENG ; Yang ZHOU
Journal of Integrative Medicine 2025;23(4):382-389
OBJECTIVE:
The concept of constitution in traditional Chinese medicine (TCM) has been increasingly recognized as a crucial factor in both the prevention and treatment of insomnia. However, rigorous statistical evidence on the correlation between TCM constitutions-particularly mixed constitutions-and insomnia disorder remains limited. This study aimed to investigate the association between specific TCM constitutions and insomnia disorder.
METHODS:
A cross-sectional study was conducted at the Department of Preventive Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, from November 2022 to December 2023. TCM constitutions were assessed using the Constitution in Chinese Medicine Questionnaire. Insomnia disorder was diagnosed by experienced internal medicine physicians according to the criteria of the International Classification of Sleep Disorders, Third Edition. A total of 1065 eligible participants (242 with insomnia disorder and 823 controls) were included in the final analysis.
RESULTS:
Among the participants, 862 (80.94%) exhibited biased constitutions, with 75.30% of these having mixed constitutions. Logistic regression analysis revealed a negative association between the gentleness constitution and insomnia disorder, whereas qi-deficiency, yang-deficiency, phlegm-dampness and qi-depression constitutions were positively associated with insomnia disorder. These associations remained significant after adjusting for potential confounders and were further validated through sensitivity analysis using propensity score matching.
CONCLUSION
Significant associations between TCM constitutions and insomnia disorder were demonstrated. Future research should further investigate these relationships and explore the underlying mechanisms through rigorous longitudinal and interventional studies to improve understanding and clinical applications. Please cite this article as: Han Y, Wang Y, Shi MY, Liu Y, Cheng XD, Zhou Y. Integrating traditional Chinese medicine constitutions into insomnia management: Findings from a cross-sectional study. J Integr Med. 2025; 23(4): 382-389.
Humans
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Sleep Initiation and Maintenance Disorders/therapy*
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Cross-Sectional Studies
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Medicine, Chinese Traditional/methods*
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Male
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Female
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Middle Aged
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Adult
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Aged
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Surveys and Questionnaires
6.Association of Body Mass Index with All-Cause Mortality and Cause-Specific Mortality in Rural China: 10-Year Follow-up of a Population-Based Multicenter Prospective Study.
Juan Juan HUANG ; Yuan Zhi DI ; Ling Yu SHEN ; Jian Guo LIANG ; Jiang DU ; Xue Fang CAO ; Wei Tao DUAN ; Ai Wei HE ; Jun LIANG ; Li Mei ZHU ; Zi Sen LIU ; Fang LIU ; Shu Min YANG ; Zu Hui XU ; Cheng CHEN ; Bin ZHANG ; Jiao Xia YAN ; Yan Chun LIANG ; Rong LIU ; Tao ZHU ; Hong Zhi LI ; Fei SHEN ; Bo Xuan FENG ; Yi Jun HE ; Zi Han LI ; Ya Qi ZHAO ; Tong Lei GUO ; Li Qiong BAI ; Wei LU ; Qi JIN ; Lei GAO ; He Nan XIN
Biomedical and Environmental Sciences 2025;38(10):1179-1193
OBJECTIVE:
This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study.
METHODS:
A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants.
RESULTS:
Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m 2) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m 2) and obesity (≥ 28.0 kg/m 2) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m 2 ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses.
CONCLUSION
This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans
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Body Mass Index
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China/epidemiology*
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Male
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Female
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Middle Aged
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Prospective Studies
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Rural Population/statistics & numerical data*
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Aged
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Follow-Up Studies
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Adult
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Mortality
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Cause of Death
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Obesity/mortality*
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Overweight/mortality*
7.Comparative analysis of isolated male epispadias: concealed versus nonconcealed cases in a Chinese tertiary hospital.
Jia-Yi LI ; Bo YU ; Meng-Cheng YANG ; Zong-Han LI ; Hong-Cheng SONG ; Wei-Ping ZHANG
Asian Journal of Andrology 2025;27(4):502-507
Isolated male epispadias typically presents with preputial defects and dorsal urethral dehiscence. A less common subtype, known as concealed epispadias, is distinguished by an intact prepuce. Despite its clinical relevance, there is limited literature on this variant. In this study, we retrospectively analyzed the clinical data of 86 pediatric patients with isolated male epispadias treated in Beijing Children's Hospital (Beijing, China) from May 2004 to July 2023, including 19 cases of concealed epispadias and 67 of nonconcealed epispadias. We compared clinical characteristics, preoperative diagnostics, surgical techniques, postoperative outcomes, and sexual function during follow-up between the concealed and nonconcealed groups. No significant differences were observed between the two groups regarding surgical methods, postoperative complications, or rates of urinary incontinence. However, notable distinctions were found in the age at initial diagnosis, timing of surgery, frequency of incontinence, location of the urethral meatus, and postoperative urinary incontinence scores (all P < 0.05). Given the absence of penopubic epispadias in concealed cases, we categorized glans and penile epispadias within nonconcealed epispadias as distal epispadias ( n = 40) and subsequently compared them with concealed epispadias cases. The postoperative urinary incontinence scores did not differ significantly between the concealed and distal epispadias groups. These findings suggest that concealed epispadias represents a relatively milder form of the condition, characterized by the absence of penopubic involvement, lower rates of urinary incontinence, and favorable surgical outcomes. However, the intact prepuce in concealed cases underscores the need for careful identification and early diagnosis.
Humans
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Male
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Retrospective Studies
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Epispadias/classification*
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China
;
Tertiary Care Centers
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Child, Preschool
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Child
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Postoperative Complications/epidemiology*
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Urinary Incontinence/epidemiology*
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Urethra/surgery*
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Infant
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Penis/surgery*
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Adolescent
;
Urologic Surgical Procedures, Male/methods*
;
East Asian People
8.Risk factors for cardiopulmonary dysfunction after ligation of hemodynamically significant patent ductus arteriosus in preterm infants.
Chong-Chong LIU ; Yong LIU ; Yi ZHANG ; Dai-Cheng HAN ; Rui-Jing HE ; Shi-Wen XIA
Chinese Journal of Contemporary Pediatrics 2025;27(4):425-431
OBJECTIVES:
To investigate the risk factors for the occurrence of cardiopulmonary dysfunction following ligation of hemodynamically significant patent ductus arteriosus (hsPDA) in preterm infants.
METHODS:
A retrospective collection of clinical data was conducted on preterm infants with a gestational age of <34 weeks who were admitted to the Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology from January 2018 to August 2024. These infants underwent hsPDA ligation after 1-2 courses of failed ibuprofen treatment. Based on the occurrence of blood pressure changes and oxygenation or ventilation failure postoperatively, the infants were divided into a cardiopulmonary dysfunction group (19 cases) and a non-cardiopulmonary dysfunction group (40 cases). Binary logistic regression analysis was performed to explore risk factors for postoperative cardiopulmonary dysfunction.
RESULTS:
Binary logistic regression analysis indicated that a faster average weight gain rate preoperatively and low levels of free triiodothyronine (FT3) within one week before surgery were risk factors for cardiopulmonary dysfunction following hsPDA ligation (P<0.05). Receiver operating characteristic curve analysis showed that an average weight gain rate >11.45 g/(kg·d) and FT3 levels <2.785 pmol/L within one week before surgery had predictive value for postoperative cardiopulmonary dysfunction (P<0.05). The combination of these two indicators provided the highest predictive value (P<0.05), with an area under the curve of 0.825, a sensitivity of 79%, and a specificity of 75%.
CONCLUSIONS
An average weight gain rate exceeding 11.45 g/(kg·d) and FT3 levels below 2.785 pmol/L within one week before surgery are risk factors affecting cardiopulmonary function after hsPDA ligation. Preoperative assessment and intervention should be strengthened to reduce the risk of postoperative complications.
Humans
;
Ductus Arteriosus, Patent/physiopathology*
;
Risk Factors
;
Female
;
Infant, Newborn
;
Male
;
Retrospective Studies
;
Infant, Premature
;
Ligation/adverse effects*
;
Hemodynamics
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Postoperative Complications/etiology*
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Logistic Models
;
Lung Diseases/etiology*
9.Comprehensive Review on Rhodiola crenulata: Ethnopharmacology, Phytochemistry, Pharmacological Properties and Clinical Applications.
Rui ZHU ; Cui-Fen FANG ; Shu-Jing ZHANG ; Zhu HAN ; Ge-Hui ZHU ; Shang-Zuo CAI ; Cheng ZHENG ; Yu TANG ; Yi WANG
Chinese journal of integrative medicine 2025;31(8):752-759
10.A comparison and prediction study of wide-field swept-source optical coher-ence tomography angiography in identifying non-perfusion areas in diabetic retinopathy
Chuyun GUO ; Yue HAN ; Li CHEN ; Yi LIU ; Hongzhuang CHENG ; Xinru NING ; Yadan SHEN ; Ruolan LING ; Jie ZHONG ; Jie LI
Recent Advances in Ophthalmology 2025;45(3):211-215
Objective To compare the differences between swept-source optical coherence tomography angiography(SS-OCTA)and ultra-wide-field fluorescein angiography(UWFA)in detecting non-perfusion areas(NPs)in patients with diabetic retinopathy(DR),to evaluate the accuracy of SS-OCTA in predicting NPs outside its visible range,and to explore the distribution patterns of NPs.Methods A retrospective analysis was made on 69 DR patients(88 eyes)who under-went both UWFA and SS-OCTA examinations at the Ophthalmology Department of Sichuan Provincial People's Hospital from December 2022 to September 2024.Manual NP labeling was conducted to compare the detection rate of NPs between the two imaging techniques.The distribution patterns of NPs and the accuracy of SS-OCTA for predicting NPs outside its visible range were also analyzed.Results In a scanning area of 20 mm x 24 mm,the overall NP detection rate by SS-OCTA was 47.40%,with UWFA taken as the standard.The NP detection rate by SS-OCTA was 51.56%in the superotemporal quad-rant,58.35%in the inferotemporal quadrant,45.50%in the superonasal quadrant,and 43.17%in the inferonasal quad-rant.Most NPs occurred in the inferonasal quadrant,accounting for 41.71%of the total NP.The accuracy of SS-OCTA in predicting NPs was 75.00%in the superonasal quadrant and 78.41%in the inferonasal quadrant.The ischemic indices(ISI)of the two imaging techniques were highly positively correlated(r2=0.74).Conclusion Although SS-OCTA can-not yet fully replace UWFA for NP detection in DR patients due to a small visible range,it is still an effective tool to assess retinal ischemia.SS-OCTA has the ability to predict NPs outside its visible range in its scanning range.The inferonasal quadrant is the region where NPs occur most frequently in DR patients,so it is suggested that special attention should be paid to this region in early diagnosis and follow-up periods.

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