OBJECTIVE: Chromosome conformation-based karyotype analysis (C-MoKa) technology was used to test a couple who had experienced multiple adverse pregnancies in order to provide them with genetic counseling and reproductive guidance. METHODS: A couple presented at the Reproductive Medicine Center of the First Hospital of Lanzhou University in 2023 was selected as the study subject. Through C-MoKa testing, copy number variation sequencing (CNV-seq), and preimplantation genetic testing for aneuploidy (PGT-A), it was found that the couple's repeatedly miscarried fetuses and abnormal embryos exhibited highly similar chromosomal structural abnormalities. Using C-MoKa, the potential genetic abnormalities in both partners were traced, and reproductive guidance was provided based on the result. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: LDYYSZLLKH2025-09). RESULTS: CNV-seq analysis of the couple's miscarriage fetal chorionic villi showed del(18)(q21.2q23)(28.90 Mb) and dup(13)(q31.2q34)(26.26 Mb). Chromosomal karyotyping analysis of both partners showed no abnormality. From 2024 to 2025, the couple underwent three rounds of PGT-A assisted reproduction. The first embryo test showed del(13)(q31.2q34)(26.77 Mb) and dup(18)(q21.2q23)(29.08 Mb). The second embryo test showed dup(13)(q31.2q34)(26.26 Mb) and del(18)(q21.2q23)(28.90 Mb). And the third embryo test results showed complex chromosomal abnormalities. In 2025, after genetic counseling, the couple had opted C-MoKa test, which has detected no abnormality in the wife, but a balanced 46,XY,t(13;18)(q31.2;q21.2) translocation in the husband. CONCLUSION As a high-throughput sequencing method based on the three-dimensional conformation of chromatin, C-MoKa has the advantages of high resolution and high accuracy, and can accurately detect balanced translocations with similar banding patterns. It has therefore offered a powerful new tool for chromosomal analysis.
Female ; Humans ; Male ; Pregnancy ; Abortion, Habitual/genetics* ; DNA Copy Number Variations ; Karyotyping/methods* ; Preimplantation Diagnosis ; Translocation, Genetic

ObjectiveTo investigate the effects of atorvastatin （ATV） on the proliferation and differentiation of rat bone marrow mesenchymal stem cells （BMSCs）， periodontal ligament stem cells （PDLSCs）， and dental pulp stem cells （DPSCs） in vitro， and to validate the regulatory effect of ATV on periodontal bone formation and tooth movement using a rat orthodontic tooth movement （OTM） model. MethodsThe effects of ATV on the proliferation and osteogenic/odontogenic differentiation of rat BMSCs， PDLSCs， and DPSCs were assessed in vitro. CCK-8 assay was used to detect the proliferation of the three types of cells. Alkaline phosphatase （ALP） staining and Alizarin Red staining were employed to evaluate osteogenic differentiation capacity. Western blot was used to detect the expression of osteogenesis-related proteins ［collagen type I （COL-I）， Runt-related transcription factor 2 （Runx2）， bone morphogenetic protein-2 （BMP-2）， osteocalcin （OCN）］ and the odontogenesis-related protein dentin sialophosphoprotein （DSPP） in BMSCs， PDLSCs and DPSCs. An OTM rat model was established， with rats randomly assigned to an ATV gavage group and a control group. The ATV gavage group received daily oral administration of ATV at a dose of 20 mg/kg， while the control group received an equal volume of solvent by gavage. Tooth movement distance was measured via Micro-CT on days 7， 14， and 21. Histomorphology of periodontal tissues was observed using Hematoxylin and Eosin （HE） staining and Masson staining. The gene and protein expression levels of osteogenic markers （BMP-2， Runx2， OCN） on the tension side of the first molar were detected by qRT-PCR and immunohistochemistry， respectively. ResultsATV at concentrations of 1×10⁻⁶ mol/L and 1×10⁻⁷ mol/L significantly promoted the proliferation and osteogenic/odontogenic differentiation of BMSCs， PDLSCs， and DPSCs， manifested as enhanced ALP activity， increased mineralized nodule formation， and up-regulated expression of osteogenic/odontogenic proteins COL-I， Runx2， BMP-2， OCN， and DSPP （P<0.001）. In the OTM model， compared with the control group， the ATV gavage group showed a significant reduction in tooth movement distance （P<0.05）， enhanced osteogenic activity in periodontal tissues， and significantly increased gene （P<0.001） and protein （P<0.05） expression of BMP-2， Runx2， and OCN on the tension side of the first molar. ConclusionATV enhances periodontal osteogenesis by promoting osteogenic/dentinogenic differentiation， thus inhibiting tooth movement.

Neonatal diabetes mellitus （NDM） is a rare monogenic disorder primarily caused by insufficient insulin secretion resulting from mutations in the KCNJ11 and ABCC8 genes. Sulfonylureas， represented by glibenclamide， have become the standard therapy for this type of NDM by precisely closing the mutated ATP-sensitive potassium channels in pancreatic β cells， thereby restoring insulin secretion. Clinical studies confirm that sulfonylureas enable over 90% of patients to successfully transition from insulin to oral treatment， achieving long-term stable glycemic control and improving neurological outcomes to a certain extent. In terms of safety， severe hypoglycemia induced by sulfonylureas is relatively rare and gastrointestinal reactions are mild； moreover， sulfonylureas show good long-term tolerability， and have no adverse effects on child growth and development. In the future， by further refining the full-chain management pathway of “rapid genetic diagnosis-early intervention-specialized dosage forms-long-term follow-up”， the clinical application of sulfonylureas is expected to provide NDM patients with an optimized treatment regimen and maximize their health benefits.

Objective: To evaluate the methodological quality and reporting quality of clinical practice guidelines or expert consensus on blood transfusion and blood use (BTBU) in China (hereinafter referred to as "guidelines/consensus"), providing reference for the development and updating of future BTBU guidelines/consensus. Methods: A systematic search was conducted in Chinese databases such as China National Knowledge Infrastructure (CNKI), Wanfang Data, VIP Data-base, relevant guideline release platforms, and professional association websites. BTBU-related guidelines/consensus published between January 2006 and December 2025 were included. According to the inclusion and exclusion criteria, after completing literature screening and data extraction, three evaluators independently assessed the quality of the included literature using the Scientificity, Transparency, and Applicability of Guidelines Rating Tool (STAR), the Appraisal of Guidelines for Research and Evaluation Ⅱ (AGREE Ⅱ), and the International Practice Guideline Reporting Standards (RIGHT). Results: A total of 29 documents were included, including 5 guidelines, 22 consensus statements, and 2 protocols. The results of the STAR assessment showed that the total score was (21.7±8.8)%. The domain score ratios for registration, research protocol, funding, working group, conflict of interest, clinical question, evidence, consensus method, recommendation, accessibility and other domains were (2.2±12.1)%, 0, (36.7±25.1)%, (18.3±7.6)%, (19.2±15.3)%, (16.6±23.1)%, (15.1±6.3)%, (9.6±21.2)%, (54.3±18.4)%, (31.7±10.4)% and (10.3±31.0)%, respectively. For the AGREE Ⅱ assessment, the methodological quality of 26 articles was rated Grade B and 3 articles Grade C. The results of the RIGHT assessment indicated that the overall reporting rate of all guidelines/consensuses was (65.3±4.0)%. Conclusion: The methodological and reporting quality of current expert guidelines/consensus on BTBU in China still need improvement, and guidelines and consensus should be strictly formulated and standardized according to the standards of STAR, AGREE II and RIGHT.

Anti-CD20 monoclonal antibodies for the treatment of refractory nephrotic syndrome （RNS） in children. The first- generation rituximab is the most widely used in clinical practice； it shows definite efficacy in children with RNS， is recommended by guidelines， particularly for achieving a high remission rate in minimal change nephrosis， and can significantly reduce the cumulative use of glucocorticoids and immunosuppressants. The second-generation ofatumumab has potential as an alternative treatment for patients who are intolerant or resistant to rituximab， while the third-generation obinutuzumab has shown efficacy in complex cases such as rituximab resistance or post-transplant recurrence. However， there is still controversy regarding the optimization of rituximab treatment dosage and whether ofatumumab and obinutuzumab offer greater advantages than rituximab for the treatment of RNS in children. The most common adverse reaction induced by anti-CD20 monoclonal antibodies is infusion reactions， and long-term adverse events mainly include increased risks of sustained immunosuppression and infections. Rituximab has significant economic advantages for the treatment of RNS， but additional pharmacoeconomic research based on China’s healthcare environment is needed to evaluate the cost-effectiveness of ofatumumab and obinutuzumab in this population. Given that the current use of ofatumumab and obinutuzumab in this field is considered off-label use， clinical application should only proceed after a rigorous evaluation of the patient’s benefits and risks.

Objective: To investigate the genetic basis of RhD-negative phenotype in the blood donor population of Nantong City. Methods: RHD genotyping was performed on 386 randomly selected RhD-negative donor samples (from a total of 676 RhD-negative donors identified between January 20, 2023, and June 28, 2024) using polymerase chain reaction (PCR), and the inconclusive results were confirmed by nucleotide sequencing. Results: Ten RHD allele types were identified: The complete deletion variant RHD 01N.01 was predominant (64.25%, 248/386); followed by RHD 01EL.01 (19.69%, 76/386). RHD 01N.03, RHD 01N.04, RHD 01N.16 and RHD 01EL.32 were frequently observed., RHD 01EL.02, RHD 01EL.08, RHD 01EL.37 and RHD 01N.25 were rare, and two exon deletion variants remained uncharacterized. The phenotypic distribution of RhD-negative blood donors was ccee (55.44%)>Ccee(31.09%)>ccEe(5.96%)>CCee(5.44%)>CcEe(1.81%)>CcEE(0.26%), and the antigen distribution trend was e(99.74%)>c(94.56%)>C(38.60%)>E(8.03%). A correlation was observed between RHD genotypes and RhCE phenotypes. Conclusion: The Nantong blood donor population exhibits unique RHD gene polymorphisms. Integrating RhCE serological phenotyping with RHD genotyping is essential for ensuring transfusion safety.

Primary liver cancer is one of the most common malignant tumors of the digestive system， and the “inflammation-to-cancer transformation” （ICT） of chronic hepatitis is the core pathological process of the progression of chronic hepatitis to liver cancer. Persistent and uncontrolled liver inflammation in patients with chronic hepatitis often leads to repeated liver tissue damage and repair， which gradually develops into liver fibrosis and cirrhosis， eventually leading to malignant transformation through the mechanisms such as gene mutation and microenvironment imbalance. ICT in chronic hepatitis is the key link between chronic hepatitis and liver cancer， and its dynamic evolution involves various pathogenic factors such as dampness， heat， deficiency， toxin， and stasis； among which damp-heat and vital energy deficiency are the initiating factors for ICT of chronic hepatitis， while intermingled stasis and toxin are the key pathological products that promote malignant transformation. Based on the concept of preventive treatment， traditional Chinese medicine can effectively delay and even block the ICT of chronic hepatitis by regulating inflammation， metabolism， and abnormal cell proliferation through multiple targets， which provides important strategies and research directions for the prevention and treatment of liver cancer.

Intrauterine growth restriction(IUGR),which refers to the failure of the fetus to achieve ad-equate growth potential,is a common complication of pregnancy.The disease seriously affects fetal growth and development,increases the risk of fetal and neonatal complications and death,and easily causes adverse perina-tal outcomes such as fetal distress and neonatal asphyxia.Children with IUGR have a high risk of lifelong neu-rodevelopmental consequences such as cognitive deficits,cerebral palsy,behavioral problems,learning and con-centration difficulties.Currently,there is no definite treatment method to protect neonates with IUGR from adverse neurological consequences.Early and accurate identification and intervention to promote neurodevelop-ment are essential to improve poor outcomes in neonates with IUGR.In addition,IUGR can also affect blood flow in the fetal brain,change the structure of the ventricles,affect brain functions and change molecular dy-namics indicators in the brain.The purpose of this article is to summarize the progress of research on fetal neurodevelopment of IUGR in recent years,and to review how IUGR affects fetal neurodevelopment and the corresponding diagnostic monitoring methods,so as to provide new ideas for further determining the plan to improve the long-term poor neurological prognosis.

Objective:To explore the effects of Jianpi Mixture on the glucose receptor/glucagon like peptide-1 (GLP-1)/5-hydroxytryptamine (5-HT) signaling pathway and the mechanism of Jianpi Mixture in improving visceral hypersensitivity in diarrhea-predominant irritable bowel syndrome (IBS-D) rats.Methods:Totally 40 healthy male SPF rats were divided into blank group, model group, Jianpi Mixture low- and high-dosage groups according to the random number table method, with 10 rats in each group. Except for the blank group, the rest of the rats were prepared by the "senna gavage combined with restraint stress" method to replicate the IBS-D spleen deficiency model. The aqueous extract of Jianpi Mixture was 2.52 and 7.56 g/kg in the low- and high-dosage groups, and the same volume of normal saline was given to the blank group and the model group, once a day, for 14 days. On the 1st, 7th and 14th days of administration, the body weight of rats was recorded, the fecal traits of the rats were scored with Bristol score, the visceral sensitivity of IBS-D rats was evaluated by the abdominal wall retraction reflex score (AWR) under rectal dilation, the morphology of colonic mucosal tissues was observed by HE staining, and the protein expressions of T1R2, SLGT1, GLUT2, GLP-1 and 5-HT in colon tissues were detected by immunohistochemical staining.Results:On the 1st, 7th and 14th days of administration, compared with the model group, the weight of the rats in the Jianpi Mixture high-dosage group increased ( P<0.05); on the 14th day of administration, the fecal Bristol score decreased significantly ( P<0.05) and the AWR score increased ( P<0.05); HE staining showed that the mucosal epithelium of colon tissue in the model group was slightly damaged, and local edema was visible. The pathological condition of colonic mucosa in the Jianpi Mixture low- and high-dosage groups was effectively improved; compared with the model group, the expressions of T1R2 and GLP-1 in the Jianpi Mixture low- and high-dosage groups increased ( P<0.05), and the expression of 5-HT decreased ( P<0.05); the protein expressions of GLUT2 and SGLT1 in the Jianpi Mixture high-dosage group increased ( P<0.05). Conclusion:Jianpi Mixture can treat spleen-deficiency IBS-D by restoring the normal expression of intestinal glucose receptors, regulating the secretion of GLP-1/5-HT, improving intestinal motility and alleviating visceral hypersensitivity.