1.Effect of Chaihu Jia Longgu Muli Decoction on apoptosis in rats with heart failure after myocardial infarction through IκBα/NF-κB pathway.
Miao-Yu SONG ; Cui-Ling ZHU ; Yi-Zhuo LI ; Xing-Yuan LI ; Gang LIU ; Xiao-Hui LI ; Yan-Qin SUN ; Ming-Yuan DU ; Lei JIANG ; Chao-Chong YUE
China Journal of Chinese Materia Medica 2025;50(8):2184-2192
This study aims to explore the protective effect of Chaihu Jia Longgu Muli Decoction on rats with heart failure after myocardial infarction, and to clarify its possible mechanisms, providing a new basis for basic research on the mechanism of classic Chinese medicinal formula-mediated inflammatory response in preventing and treating heart failure induced by apoptosis after myocardial infarction. A heart failure model after myocardial infarction was established in rats by coronary artery ligation. The rats were divided into sham group, model group, and low, medium, and high-dose groups of Chaihu Jia Longgu Muli Decoction, with 10 rats in each group. The low-dose, medium-dose, and high-dose groups of Chaihu Jia Longgu Muli Decoction were given 6.3, 12.6, and 25.2 g·kg~(-1) doses by gavage, respectively. The sham group and model group were given an equal volume of distilled water by gavage once daily for four consecutive weeks. Cardiac function was assessed using color Doppler echocardiography. Myocardial pathology was detected by hematoxylin-eosin(HE) staining, apoptosis was measured by TUNEL assay, and mitophagy was observed by transmission electron microscopy. The levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-1β, and N-terminal pro-B-type natriuretic peptide(NT-proBNP) in serum were detected by enzyme-linked immunosorbent assay(ELISA). The expression of apoptosis-related proteins B-cell lymphoma 2(Bcl-2), Bcl-2-associated X protein(Bax), and cleaved caspase-3 was detected by Western blot. Additionally, the expression of phosphorylated nuclear transcription factor-κB(NF-κB) p65(p-NF-κB p65)(upstream) and nuclear factor kappa B inhibitor alpha(IκBα)(downstream) in the NF-κB signaling pathway was assessed by Western blot. The results showed that compared with the sham group, left ventricular ejection fraction(LVEF) and left ventricular short axis shortening(LVFS) in the model group were significantly reduced, while left ventricular end diastolic diameter(LVEDD) and left ventricular end systolic diameter(LVESD) increased significantly. Myocardial tissue damage was severe, with widened intercellular spaces and disorganized cell arrangement. The apoptosis rate was increased, and mitochondria were enlarged with increased vacuoles. Levels of TNF-α, IL-1β, and NT-proBNP were elevated, indicating an obvious inflammatory response. The expression of pro-apoptotic factors Bax and cleaved caspase-3 increased, while the anti-apoptotic factor Bcl-2 decreased. The expression of p-NF-κB p65 was upregulated, and the expression of IκBα was downregulated. In contrast, the Chaihu Jia Longgu Muli Decoction groups showed significantly improved of LVEF, LVFS and decreased LVEDD, LVESD compared to the model group. Myocardial tissue damage was alleviated, and intercellular spaces were reduced. The apoptosis rate decreased, mitochondrial volume decreased, and the levels of TNF-α, IL-1β, and NT-proBNP were lower. The expression of pro-apoptotic factors Bax and cleaved caspase-3 decreased, while the expression of the anti-apoptotic factor Bcl-2 increased. Additionally, the expression of p-NF-κB p65 decreased, while IκBα expression increased. In summary, this experimental study shows that Chaihu Jia Longgu Muli Decoction can reduce the inflammatory response and apoptosis rate in rats with heart failure after myocardial infarction, which may be related to the regulation of the IκBα/NF-κB signaling pathway.
Animals
;
Apoptosis/drug effects*
;
Drugs, Chinese Herbal/administration & dosage*
;
Rats
;
Myocardial Infarction/physiopathology*
;
Male
;
NF-kappa B/genetics*
;
Heart Failure/etiology*
;
Rats, Sprague-Dawley
;
Signal Transduction/drug effects*
;
NF-KappaB Inhibitor alpha/genetics*
;
Humans
;
Tumor Necrosis Factor-alpha/genetics*
2.Molecular targeted therapy for progressive low-grade gliomas in children.
Yan-Ling SUN ; Miao LI ; Jing-Jing LIU ; Wen-Chao GAO ; Yue-Fang WU ; Lu-Lu WAN ; Si-Qi REN ; Shu-Xu DU ; Wan-Shui WU ; Li-Ming SUN
Chinese Journal of Contemporary Pediatrics 2025;27(6):682-689
OBJECTIVES:
To evaluate the efficacy of molecular targeted agents in children with progressive pediatric low-grade gliomas (pLGG).
METHODS:
A retrospective analysis was conducted on pLGG patients treated with oral targeted therapies at the Department of Pediatrics, Beijing Shijitan Hospital, Capital Medical University, from July 2021. Treatment responses and safety profiles were assessed.
RESULTS:
Among the 20 enrolled patients, the trametinib group (n=12, including 11 cases with BRAF fusions and 1 case with BRAF V600E mutation) demonstrated 4 partial responses (33%) and 2 minor responses (17%), with a median time to response of 3.0 months. In the vemurafenib group (n=6, all with BRAF V600E mutation), 5 patients achieved partial responses (83%), showing a median time to response of 1.0 month. Comparative analysis revealed no statistically significant difference in progression-free survival rates between the two treatment groups (P>0.05). The median duration of clinical benefit (defined as partial response + minor response + stable disease) was 11.0 months for vemurafenib and 18.0 months for trametinib. Two additional cases, one with ATM mutation treated with olaparib for 24 months and one with NF1 mutation receiving everolimus for 21 months, discontinued treatment due to sustained disease stability. No severe adverse events were observed in any treatment group.
CONCLUSIONS
Molecular targeted therapy demonstrates clinical efficacy with favorable tolerability in pLGG. Vemurafenib achieves high response rates and induces early tumor shrinkage in patients with BRAF V600E mutations, supporting its utility as a first-line therapy.
Humans
;
Glioma/genetics*
;
Male
;
Female
;
Child
;
Child, Preschool
;
Retrospective Studies
;
Brain Neoplasms/genetics*
;
Molecular Targeted Therapy/adverse effects*
;
Adolescent
;
Infant
;
Proto-Oncogene Proteins B-raf/genetics*
;
Pyrimidinones/therapeutic use*
;
Mutation
3.Analysis of biotypes and genetic diversity of five non-major pathogenic Brucella species
Miao WANG ; Ying-qi WANG ; Chun-fang LIU ; Song-nan DU ; Zhi-guo LIU ; Zhen-jun LI
Chinese Journal of Zoonoses 2025;41(2):136-141
This study was aimed at analyzing the biotypes and genetic diversity characteristics of five non-major Brucella species,to provide a scientific basis for understanding the species diversity of Brucella and strengthening pathogen monitoring and control.According to the biotypes(species,hosts,isolation locations,and time)and MLVA-16 genotypes(MLVA-16 lo-cus data,MLVA-11 genotypes)of five non-major pathogenic Brucella in the international MLVA database,we used Bionu-merics 8.0 software and PHYLOVIZ2.0 online software to analyze the geographical origin and genetic diversity characteristics of strains.A total of 227 strains were studied,including 121 Brucella ceti,47 B.pinnipedialis,37 Brucella ovis,11 B.mi-croti,and Brucella neotomae.The greatest host diversity was observed for B.ceti,followed by B.pinnipedialis and B.mi-croti.B.ceti was distributed in European and South American countries;B.pinnipedialiswas distributed in Europe;and B.microti.was distributed in the Czech Republic,Austria,and Hungary in Central Europe.B.ovis was widely distributed in Af-rica,Argentina,Australia,Brazil,Greece,the United States,Spain,and France.The MLVA-11 genotypes of different types of Brucella showed high polymorphism and large differences,thus suggesting that the strains have different geographical ori-gins.MST analysis indicated that the studied strains were divided into four branches(BCⅠ-Ⅳ),among which B.ceti was di-vided into two different branches(BC-Ⅰ and BC-Ⅱ),the strains of other types formed different branches(or sub-branches),and the strains of different types showed clear regional and dominant host characteristics.Genetic correlation analysis of strains of the Brucella genus revealed that non-major pathogenic Brucella had clear genetic,distribution,and host spectrum differ-ences with respect to four classical pathogenic Brucella species.Five non-major pathogenic Brucella strains presented unique genetic evolutionary patterns,geographical distributions,and host tropism characteristics,thereby providing new insight for understanding the biological and genetic diversity of those Brucella strains.
4.Genetic analysis of 74 fetuses terminated for skeletal dysplasia and evaluation of diagnostic performance of whole exome sequencing
Jiashan LI ; Siying LIANG ; Yan MIAO ; Xiaoyu DU ; Meiyan HAN ; Wei ZHAO ; Nan JIANG ; Yingchao ZHOU
Chinese Journal of Medical Genetics 2025;42(7):869-882
Objective:To explore the genetic etiology of fetal skeletal dysplasia using whole exome sequencing (WES) and copy number variation sequencing (CNV-seq) techniques, and the feasibility of using WES as the first-tier method for such fetuses.Methods:Seventy four fetuses with skeletal dysplasia detected by prenatal ultrasound at the Genetic Testing Center of the Women and Children′s Hospital Affiliated to Qingdao University from January 2020 to August 2024 were selected as the study subjects. Fetal muscle and peripheral blood samples of the pregnant women and their spouses were collected and subjected to WES analysis. CNV-seq was carried out on all fetal muscle tissue samples. And the results were compared with the CNVs indicated by WES. Genetic etiologies were analyzed across different subtypes of skeletal dysplasia. And the feasibility of using WES as the first-tier genetic test for similar fetuses was assessed, in addition with a systematic cost-effectiveness analysis. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: QFELL-YJ-2024-201).Results:A total of 50 fetuses were diagnosed, which yielded a diagnostic rate of 67.57%. These included 6 chromosomal aneuploidies, 4 chromosomal CNVs and 40 monogenic disorders. The monogenic diseases had involved 46 variant sites in 23 pathogenic genes, among which 12 were unreported previously, including MYH3: c. 735T>C, ALPL: c. 1324C>T, NEK9: c. 1973G>A, MAGEL2: c. 2024_2025del, LMBR1: c. 423+ 4914A>C, NEB: c. 21273_21276del, COL1A1: c. 2651G>C and c. 2758G>C, ASPM: c. 2473delinsGA, TBX5: c. 704G>A, DYNC2H1: c. 10893del, and DYNC2I2: c. 1270C>T. Substantial concordance was reached between WES-derived CNV calls and CNV-seq findings. No clinically significant CNV was exclusively detected by CNV-seq. Cost-effectiveness modeling demonstrated that implementing WES as the first-tier genetic testing method could reduce the total expenditure when WES unit cost remained below 6.4 folds that of the CNV-seq. Conclusion:Genetic variants including single nucleotide variations (SNV) of monogenic disorders, chromosomal aneuploidies and genomic CNVs are important causes for fetal skeletal dysplasia. WES is an accurate and efficient method for analyzing the etiology of fetal skeletal dysplasia, particularly in those with a family history of similar phenotype or maternal history of adverse pregnancies.
5.Application of chromosomal microarray analysis in the prenatal diagnosis of fetuses with isolated Congenital anomalies of the kidney and urinary tract
Xiaoyu DU ; Yan MIAO ; Jiashan LI ; Siying LIANG ; Wei ZHAO ; Yingchao ZHOU ; Nan JIANG
Chinese Journal of Medical Genetics 2025;42(9):1033-1038
Objective:To explore the detection rate of copy number variations (CNVs) in fetuses with isolated Congenital anomalies of the kidney and urinary tract (CAKUT) and pregnancy outcomes in order to provide a basis for genetic counseling.Methods:One hundred and eighty eight fetuses who underwent chromosomal microarray analysis (CMA) due to isolated CAKUT detected by prenatal ultrasonography at Qingdao Women and Children′s Hospital from January 2021 to December 2024 were selected as the study subjects. According to the ultrasound findings, the fetuses were divided into 8 groups, including renal parenchymal dysplasia group, renal cystic dysplasia group, simple renal parenchymal echo enhancement group, abnormal development of renal collecting system group, duplicated kidney group, ectopic kidney group, horseshoe kidney group, and bladder/posterior urethral abnormalities group. The detection of CNVs was retrospectively analyzed, and the pregnant women were followed up to summarize their pregnancy outcomes. 2 test (or Fisher′s exact probability method) was used to compare the CNV detection rates between the groups. This study was approved by the Medical Ethics Committee of the Qingdao Women and Children′s Hospital (Ethics No.: QFELL-YJ-2025-85).Results:Among the 188 fetuses with isolated CAKUT, 23 CNVs (12.23%) were detected, of which 13 cases (6.91%) were pathogenic and 10 cases were rated as variants of unknown significance (VOUS). Among the 8 groups, the three groups with the highest proportion were renal cystic dysplasia group, renal metaplasia group, and renal parenchymal dysplasia group. The detection rates of pathogenic CNVs in the three groups were 1.79% (1/56), 6.78% (4/59), and 16.67% (5/30), respectively, with statistically significant differences ( P<0.05). Parental verification was conducted on 12 fetuses detected with the CNVs, confirming that 2 cases were de novo and 10 were inherited from parents with a normal phenotype. After genetic counseling, the parents of 9 fetuses opted to terminate the pregnancy, while 11 chose to continue with the pregnancy, and 3 were lost to follow-up. At the time of last follow-up, the youngest offspring was 5 months old and the oldest was 3 years and 11 months old. One child had renal aplasia, and two were born with hydronephrosis, which have been cured through surgery. The remainders had no obvious abnormality with their growth and development. Conclusion:CMA testing has important value for prenatal diagnosis of isolated CAKUT. In this study, the detection rate of pathogenic CNVs has increased sequentially in fetuses with renal cystic developmental abnormalities, renal collecting system developmental abnormalities, and renal parenchymal dysplasia, while there was no significant difference in the detection rate of CNVs. For fetuses with isolated CAKUT detected by prenatal ultrasound, CMA testing should be considered, and reasonable pregnancy decisions should be made based on the results of prenatal ultrasound and parental verification.
6.Advances in nanocarrier-mediated cancer therapy: Progress in immunotherapy, chemotherapy, and radiotherapy.
Yue PENG ; Min YU ; Bozhao LI ; Siyu ZHANG ; Jin CHENG ; Feifan WU ; Shuailun DU ; Jinbai MIAO ; Bin HU ; Igor A OLKHOVSKY ; Suping LI
Chinese Medical Journal 2025;138(16):1927-1944
Cancer represents a major worldwide disease burden marked by escalating incidence and mortality. While therapeutic advances persist, developing safer and precisely targeted modalities remains imperative. Nanomedicines emerges as a transformative paradigm leveraging distinctive physicochemical properties to achieve tumor-specific drug delivery, controlled release, and tumor microenvironment modulation. By synergizing passive enhanced permeation and retention effect-driven accumulation and active ligand-mediated targeting, nanoplatforms enhance pharmacokinetics, promote tumor microenvironment enrichment, and improve cellular internalization while mitigating systemic toxicity. Despite revolutionizing cancer therapy through enhanced treatment efficacy and reduced adverse effects, translational challenges persist in manufacturing scalability, longterm biosafety, and cost-efficiency. This review systematically analyzes cutting-edge nanoplatforms, including polymeric, lipidic, biomimetic, albumin-based, peptide engineered, DNA origami, and inorganic nanocarriers, while evaluating their strategic advantages and technical limitations across three therapeutic domains: immunotherapy, chemotherapy, and radiotherapy. By assessing structure-function correlations and clinical translation barriers, this work establishes mechanistic and translational references to advance oncological nanomedicine development.
Humans
;
Neoplasms/radiotherapy*
;
Immunotherapy/methods*
;
Nanoparticles/chemistry*
;
Animals
;
Nanomedicine/methods*
;
Drug Delivery Systems/methods*
;
Drug Carriers/chemistry*
;
Radiotherapy/methods*
7.Pathogenesis of precancerous lesions of gastric cancer and treatment mechanism of Weifuchun Capsules via NF-κB/NLRP3 inflammasome signaling pathway.
Yu-Jia DU ; Ya-di REN ; Yan ZHUANG ; En-Ze LI ; Jun-Hao MIAO ; Chun-Yue YU
China Journal of Chinese Materia Medica 2025;50(5):1236-1246
This study aims to investigate the pathogenesis of precancerous lesions of gastric cancer(PLGC) and explore the potential molecular mechanism of Weifuchun Capsules(WFC) in treating PLGC via the nuclear factor-κB(NF-κB)/NOD-like receptor protein 3(NLRP3) inflammasome signaling pathway. Ninety male SPF-grade Wistar rats were randomized into a normal feeding group and a modeling group. The normal feeding group received a regular diet, while the modeling group was subjected to the disease-syndrome combined modeling of PLGC. Specifically, the rats had free access to the water containing 120 μg·mL~(-1) N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) and received a diet containing 0.05% ranitidine in an irregular feeding pattern(alternations between fasting and overfeeding). After 15 weeks, the rats in the normal feeding group were randomized into control, control-NF-κB activator betulinic acid(C-BA), and control-NF-κB inhibitor pyrrolidine dithiocarbamaten(C-PDTC) groups. Meanwhile, the rats in the modeling group continuously underwent the modeling procedure and were randomized into model, WFC, model-NF-κB activator(M-BA), and model-NF-κB inhibitor(M-PDTC) groups. The model group and control group were given aseptic water by intragastric administration, once a day. WFC was given at a dose(432 mg·kg~(-1)) 6 times the equivalent dose for adults(body weight: 60 kg) by gavage, once a day. The rats in the C-BA and M-BA groups were administrated with BA by intraperitoneal injection at a dose of 10 mg·kg~(-1), twice a week. The rats in the C-PDTC and M-PDTC groups were administrated with PDTC by intraperitoneal injection at a dose of 50 mg·kg~(-1), twice a week. The interventions were carried out for 4 weeks. Histopathological changes of the gastric mucosa were observed and scored by hematoxylin-eosin(HE) and alcian blue-periodic acid Sthiff(AB-PAS) staining. The levels of inflammatory cytokines including interleukin(IL)-1β, IL-6, IL-18, tumor necrosis factor-alpha(TNF-α), and IL-10 in the gastric tissue were determined by enzyme-linked immunosorbent assay(ELISA). The expression levels of proteins associated with the NF-κB/NLRP3 inflammasome in the gastric mucosa were determined by Western blot. The positive expression areas of proteins related to NF-κB/NLRP3 inflammasome in the gastric mucosa were measured by immunohistochemistry. The results showed that compared with the control group, the model, C-BA, and M-BA groups showed significantly risen scores of mucosal inflammation, degree of inflammatory activity, gland atrophy, and intestinal metaplasia, and the model and M-BA groups showed significanly risen scores of dysplasia. Compared with the model group, the WFC group demonstrated significantly declined scores of mucosal inflammation and degree of inflammatory activity, as well as declined scores of intestinal metaplasia and dysplasia. Compared with the control group, the model and C-BA groups showed significantly elevated levels of IL-1β, IL-6, IL-18, and TNF-α in the gastric tissue, and the model group showed significantly elevated level of IL-10. In addition, the model and C-BA groups showed significantly up-regulated expression of NF-κB p65, NLRP3, cysteine-aspartic acid protease 1(caspase-1), and apoptosis-associated speck-like protein containing a CARD(ASC) in the gastric mucosa and increased positive expression areas of NF-κB p65, NLRP3, and ASC. Compared with the model group, the WFC group showed significantly decreased levels of IL-1β, IL-6, IL-18, TNF-α, and IL-10 in the gastric tissue, and the M-PDTC group showed significantly lowered levels of IL-1β, IL-18, and TNF-α in the gastric mucosa. Both WFC and M-PDTC groups demonstrated significantly down-regulated expression levels of NF-κB p65, phosphorylated NF-κB p65(p-NF-κB p65), NLRP3, and caspase-1 in the gastric mucosa, along with significant decreases in the positive expression areas of NF-κB p65, NLRP3, and ASC. In conclusion, the pathogenesis of PLGC is closely related to the activation of the NF-κB/NLRP3 inflammasome signaling pathway. WFC can alleviate mucosal inflammation, inhibit glandular atrophy, partially reverse intestinal metaplasia, and reduce dysplasia to delay the process of inflammation-cancer transformation, and meanwhile it can effectively lower the levels of inflammatory cytokines and down-regulate the expression of pathway-related proteins in the stomach. Therefore, WFC may treat PLGC by inhibiting the NF-κB/NLRP3 inflammasome signaling pathway.
Animals
;
Male
;
NF-kappa B/genetics*
;
Rats
;
Rats, Wistar
;
Drugs, Chinese Herbal/administration & dosage*
;
Signal Transduction/drug effects*
;
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism*
;
Stomach Neoplasms/pathology*
;
Inflammasomes/genetics*
;
Humans
;
Precancerous Conditions/metabolism*
;
Capsules
8.Genetic analysis of 74 fetuses terminated for skeletal dysplasia and evaluation of diagnostic performance of whole exome sequencing.
Jiashan LI ; Siying LIANG ; Yan MIAO ; Xiaoyu DU ; Meiyan HAN ; Wei ZHAO ; Nan JIANG ; Yingchao ZHOU
Chinese Journal of Medical Genetics 2025;42(7):869-882
OBJECTIVE:
To explore the genetic etiology of fetal skeletal dysplasia using whole exome sequencing (WES) and copy number variation sequencing (CNV-seq) techniques, and the feasibility of using WES as the first-tier method for such fetuses.
METHODS:
Seventy four fetuses with skeletal dysplasia detected by prenatal ultrasound at the Genetic Testing Center of the Women and Children's Hospital Affiliated to Qingdao University from January 2020 to August 2024 were selected as the study subjects. Fetal muscle and peripheral blood samples of the pregnant women and their spouses were collected and subjected to WES analysis. CNV-seq was carried out on all fetal muscle tissue samples. And the results were compared with the CNVs indicated by WES. Genetic etiologies were analyzed across different subtypes of skeletal dysplasia. And the feasibility of using WES as the first-tier genetic test for similar fetuses was assessed, in addition with a systematic cost-effectiveness analysis. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: QFELL-YJ-2024-201).
RESULTS:
A total of 50 fetuses were diagnosed, which yielded a diagnostic rate of 67.57%. These included 6 chromosomal aneuploidies, 4 chromosomal CNVs and 40 monogenic disorders. The monogenic diseases had involved 46 variant sites in 23 pathogenic genes, among which 12 were unreported previously, including MYH3: c.735T>C, ALPL: c.1324C>T, NEK9: c.1973G>A, MAGEL2: c.2024_2025del, LMBR1: c.423+4914A>C, NEB: c.21273_21276del, COL1A1: c.2651G>C and c.2758G>C, ASPM: c.2473delinsGA, TBX5: c.704G>A, DYNC2H1: c.10893del, and DYNC2I2: c.1270C>T. Substantial concordance was reached between WES-derived CNV calls and CNV-seq findings. No clinically significant CNV was exclusively detected by CNV-seq. Cost-effectiveness modeling demonstrated that implementing WES as the first-tier genetic testing method could reduce the total expenditure when WES unit cost remained below 6.4 folds that of the CNV-seq.
CONCLUSION
Genetic variants including single nucleotide variations (SNV) of monogenic disorders, chromosomal aneuploidies and genomic CNVs are important causes for fetal skeletal dysplasia. WES is an accurate and efficient method for analyzing the etiology of fetal skeletal dysplasia, particularly in those with a family history of similar phenotype or maternal history of adverse pregnancies.
Humans
;
Exome Sequencing/methods*
;
Female
;
Pregnancy
;
DNA Copy Number Variations/genetics*
;
Genetic Testing/methods*
;
Prenatal Diagnosis/methods*
;
Adult
;
Male
;
Fetus
;
Bone Diseases, Developmental/diagnosis*
;
Ultrasonography, Prenatal
9.Application of chromosomal microarray analysis in the prenatal diagnosis of fetuses with isolated Congenital anomalies of the kidney and urinary tract.
Xiaoyu DU ; Yan MIAO ; Jiashan LI ; Siying LIANG ; Wei ZHAO ; Yingchao ZHOU ; Nan JIANG
Chinese Journal of Medical Genetics 2025;42(9):1033-1038
OBJECTIVE:
To explore the detection rate of copy number variations (CNVs) in fetuses with isolated Congenital anomalies of the kidney and urinary tract (CAKUT) and pregnancy outcomes in order to provide a basis for genetic counseling.
METHODS:
One hundred and eighty eight fetuses who underwent chromosomal microarray analysis (CMA) due to isolated CAKUT detected by prenatal ultrasonography at Qingdao Women and Children's Hospital from January 2021 to December 2024 were selected as the study subjects. According to the ultrasound findings, the fetuses were divided into 8 groups, including renal parenchymal dysplasia group, renal cystic dysplasia group, simple renal parenchymal echo enhancement group, abnormal development of renal collecting system group, duplicated kidney group, ectopic kidney group, horseshoe kidney group, and bladder/posterior urethral abnormalities group. The detection of CNVs was retrospectively analyzed, and the pregnant women were followed up to summarize their pregnancy outcomes. 2 test (or Fisher's exact probability method) was used to compare the CNV detection rates between the groups. This study was approved by the Medical Ethics Committee of the Qingdao Women and Children's Hospital (Ethics No.: QFELL-YJ-2025-85).
RESULTS:
Among the 188 fetuses with isolated CAKUT, 23 CNVs (12.23%) were detected, of which 13 cases (6.91%) were pathogenic and 10 cases were rated as variants of unknown significance (VOUS). Among the 8 groups, the three groups with the highest proportion were renal cystic dysplasia group, renal metaplasia group, and renal parenchymal dysplasia group. The detection rates of pathogenic CNVs in the three groups were 1.79% (1/56), 6.78% (4/59), and 16.67% (5/30), respectively, with statistically significant differences (P < 0.05). Parental verification was conducted on 12 fetuses detected with the CNVs, confirming that 2 cases were de novo and 10 were inherited from parents with a normal phenotype. After genetic counseling, the parents of 9 fetuses opted to terminate the pregnancy, while 11 chose to continue with the pregnancy, and 3 were lost to follow-up. At the time of last follow-up, the youngest offspring was 5 months old and the oldest was 3 years and 11 months old. One child had renal aplasia, and two were born with hydronephrosis, which have been cured through surgery. The remainders had no obvious abnormality with their growth and development.
CONCLUSION
CMA testing has important value for prenatal diagnosis of isolated CAKUT. In this study, the detection rate of pathogenic CNVs has increased sequentially in fetuses with renal cystic developmental abnormalities, renal collecting system developmental abnormalities, and renal parenchymal dysplasia, while there was no significant difference in the detection rate of CNVs. For fetuses with isolated CAKUT detected by prenatal ultrasound, CMA testing should be considered, and reasonable pregnancy decisions should be made based on the results of prenatal ultrasound and parental verification.
Humans
;
Female
;
Pregnancy
;
Prenatal Diagnosis/methods*
;
DNA Copy Number Variations/genetics*
;
Kidney/abnormalities*
;
Adult
;
Ultrasonography, Prenatal
;
Urogenital Abnormalities/diagnosis*
;
Microarray Analysis/methods*
;
Retrospective Studies
;
Urinary Tract/abnormalities*
;
Fetus
;
Pregnancy Outcome
;
Vesico-Ureteral Reflux
10.Clinical study on the combination of Jianpi Bushen Jiedu Prescription with 5-fluorouracil-based chemotherapy and targeted therapy for the treatment of advanced colorectal cancer
Yuying HUANG ; Juan CHEN ; Tao GONG ; Miao MA ; Yanhua ZHAO ; Zihan LIN ; Haina DU ; Xiaokang TIAN ; Mingzhi FANG ; Min LI
International Journal of Traditional Chinese Medicine 2025;47(8):1059-1065
Objective:To observe the clinical efficacy and safety of Jianpi Bushen Jiedu Prescription combined with 5-fluorouracil (5-FU)-based chemotherapy and targeted therapy for the treatment of advanced colorectal cancer patients with liver and kidney yin deficiency combined with spleen deficiency pattern.Methods:A randomized controlled trial was conducted. A total of 72 hospitalized patients with advanced colorectal cancer treated at the Department of Oncology, Nanjing Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine from October 2022 to January 2024 were enrolled as study subjects. Using a random number table method, they were allocated into two groups, with 36 patients in each group. The control group received the mFOLFOX6/FOLFIRI combined with bevacizumab regimen, while the treatment group was administered additional oral Jianpi Bushen Jiedu Prescription on the basis of the control group. Two weeks was a cycle in both groups, with a total of 6 cycles of treatment. Serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), and carbohydrate antigen 724 (CA724) were detected using electrochemiluminescence; the Karnofsky Performance Status (KPS) scale was utilized to evaluate patients' functional status; vital signs were continuously monitored, and adverse reactions were recorded. The short-term efficacy and TCM syndrome efficacy of patients were evaluated.Results:The treatment group demonstrated higher objective response rate (ORR) [31.25% (10/32) vs. 21.88% (7/32), χ2=0.72] and disease control rate (DCR) [84.38% (27/32) vs. 71.88% (23/32), χ2=1.46] compared to the control group, without statistical significance ( P>0.05). Post-treatment levels of CEA [4.09 (3.31,8.57) μg/L vs. 10.07 (4.55,22.35) μg/L, Z=-2.10] and CA72-4 [4.54 (2.04,10.99) mU/L vs. 9.48 (4.34,18.95) mU/L, Z=-2.52] in the treatment group were significantly lower than those in the control group ( P<0.05). The total effective rate of TCM syndrome was significantly higher in the treatment group [78.13% (25/32)] compared with the control group [50.00% (16/32)], with statistical significance ( χ2=5.50, P=0.019). Post-treatment KPS scores in the treatment group [80.0 (80.0, 80.0) vs. 70.0 (62.5, 80.0), Z=-2.76] were significantly higher compared with the control group ( P<0.01). During the treatment period, the treatment group showed statistical significance compared with the control group in the incidence of hemoglobin decrease ( χ2=4.66), leukopenia decrease ( χ2=4.27), and peripheral neuropathy ( χ2=3.93), with statistical significance ( P<0.05). Conclusion:The addition of Jianpi Bushen Jiedu Prescription to 5-FU-based chemotherapy combined with targeted therapy demonstrates significant clinical benefits in advanced colorectal cancer patients, including reducing tumor marker levels, alleviating clinical symptoms, improving quality of life, and mitigating treatment-related toxicities, with a good safety.

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