AIM: To explore the risk factors for postoperative anterior chamber exudation in cataract patients and construct a nomogram prediction model.METHODS: Retrospective study. From July 2019 to October 2024, 450 patients(467 eyes)with age-related cataract who underwent surgery in our hospital were collected as the study subjects. They were randomly grouped into a modeling group(315 cases, 327 eyes)and a validation group(135 cases, 140 eyes)roughly estimated at a 7:3 ratio using the random number table method. Both groups were separated into a non-exudative group and an exudative group based on whether anterior chamber exudation occurred after surgery. Clinical basic data was collected; multivariate Logistic regression was applied to analyze the influencing factors of anterior chamber exudation in patients with age-related cataract after surgery; R software was applied to draw a nomogram prediction model of anterior chamber exudation in patients with age-related cataract after surgery; the calibration curve and Hosmer Lemeshow(H-L)test were applied to evaluate the calibration of the column plot model in predicting the occurrence of anterior chamber exudation in patients with age-related cataract after surgery; ROC was applied to evaluate the efficacy of anterior chamber exudation in patients with age-related cataract after surgery.RESULTS:The clinical characteristics of the modeling group and the validation group were comparable. The high myopia, history of uveitis, preoperative intraocular pressure, lens nuclear grade, intraoperative cumulative dissipated energy, and intraoperative posterior capsular rupture of the lens were the influencing factors for postoperative anterior chamber exudation in patients with age-related cataract(all P<0.05). The results of the modeling group verifying the occurrence of anterior chamber exudation in patients with age-related cataract after surgery showed that the area under the ROC curve(AUC)was 0.986(95% CI: 0.966-0.996), the H-L test was χ2=6.494, P=0.592, indicating that the risk of anterior chamber exudation in patients with age-related cataract after surgery predicted by model had good consistency with actual risks, the AUC of postoperative anterior chamber exudation in patients with age-related cataract based on external validation was 0.982(95% CI: 0.960-0.994); and the H-L test suggested that the risk of anterior chamber exudation in CAT patients after surgery predicted by model had good consistency with actual risks(χ2=6.117, P=0.634).CONCLUSION:High myopia, history of uveitis, preoperative intraocular pressure, lens nuclear grade, intraoperative cumulative dissipated energy, and intraoperative posterior capsular rupture of the lens are risk factors for postoperative anterior chamber exudation in patients with age-related cataract; the nomogram prediction model constructed based on this has high predictive value, and can provide reference for individualized prevention of anterior chamber exudation in patients with age-related cataract after surgery.

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

Abnormal activation of the Janus kinase/signal transducer and activator of transcription （JAK/STAT） signaling pathway is involved in the pathogenesis of diffuse large B-cell lymphoma （DLBCL）. In recent years， inhibitors targeting JAK2 and STAT3 have emerged as promising therapeutic candidates in DLBCL. This review summarizes the efficacy and safety profiles of JAK2 inhibitors （e.g.， ruxolitinib） and STAT3 inhibitors （direct small-molecule inhibitors， the antisense oligonucleotide， and proteolysis targeting chimeras， etc.） in preclinical models and clinical trials. Accumulating evidence indicates that JAK2 and STAT3 inhibitors exhibit antitumor activity and are generally well tolerated in a subset of DLBCL patients. Meanwhile， the development of novel drug delivery systems has significantly enhanced the stability， bioavailability， and targeting ability of the compounds. Furthermore， JAK2 and STAT3 inhibitors may exhibit synergistic effects when combined with other therapy strategies （such as combinations with B-cell receptor signaling pathway inhibitors， immunomodulators， or other targeted drugs）. However， current clinical applications are still in their early stages. Future research should concentrate on precision treatment strategies based on the genetic subtyping of DLBCL， and further refine the delivery systems for inhibitors as well as combination drug regimens to improve clinical outcomes.

OBJECTIVE To provide references for the accurate identification and management of immune-related cutaneous adverse events （irCAEs） caused by durvalumab， and ensuring safe clinical drug use. METHODS Clinical pharmacists participated in the diagnosis and treatment process of a patient with gallbladder cancer who developed irCAEs caused by durvalumab. The clinical pharmacists systematically reviewed the patient’s past medical history and medication history， and assisted physicians in assessing the association between adverse drug reactions and administered drugs. Meanwhile， the clinical pharmacists conducted a graded assessment of the adverse reaction， proposed recommendations such as discontinuing durvalumab and adjusting the administration regimen of glucocorticoids， assisted physicians in restarting immunotherapy， and carried out medication education and other pharmaceutical care. RESULTS The occurrence of irCAEs in this patient was “highly likely” related to durvalumab and was classified as severe. The physicians adopted the clinical pharmacist’s opinion， and after symptomatic treatment， the patient’s skin symptoms improved， and discharged with medication. After the completion of glucocorticoid therapy for the patient， the physician restarted immunotherapy with tislelizumab， and no related adverse reactions occurred again in the patient. CONCLUSIONS Durvalumab can cause irCAEs such as severe skin maculopapular rash. In clinical practice， it is crucial to promptly identify and discontinue suspicious drugs， immediately implement effective symptomatic treatment measures， and actively resume immunotherapy to ensure the continuity and safety of the patient’s treatment.

ObjectiveTo investigate the value of albumin-bilirubin （ALBI） score combined with platelet count-to-spleen thickness ratio （PC/ST） in predicting rebleeding within one year after endoscopic variceal ligation in liver cirrhosis patients with esophagogastric variceal bleeding （EVB）， to evaluate the risk assessment ability of this model， and to provide a reference for clinical prevention of rebleeding. MethodsA retrospective analysis was performed on the clinical data of liver cirrhosis patients with EVB who were hospitalized in Gansu Provincial Hospital from January 1， 2020 to December 31， 2024. All patients achieved successful hemostasis after endoscopic variceal ligation， and according to whether rebleeding occurred within one year after surgery， they were divided into rebleeding group and non-rebleeding group. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The univariate and multivariate Cox regression analyses were used to identify independent influencing factors for rebleeding. A prediction model was constructed based on the factors identified， and a nomogram was plotted for model visualization. The receiver operating characteristic （ROC） curve was used to assess the discriminatory ability of the model， and the area under the ROC curve （AUC） was calculated； calibration curve was used to assess calibration； decision curve analysis was used to assess the net clinical benefit of the model. ResultsA total of 258 patients were enrolled， among whom 70 patients experienced rebleeding within one year， resulting in a rebleeding rate of 27.1%. The multivariate Cox regression analysis showed that ALBI score （hazard ratio ［HR］=4.679， 95% confidence interval ［CI］： 2.952 — 7.417， P<0.001） and PC/ST （HR=0.461， 95%CI： 0.318 — 0.668， P<0.001） were independent influencing factors for rebleeding in liver cirrhosis patients with EVB. The model constructed based on these two factors yielded an AUC of 0.766 （95%CI： 0.667 — 0.866）， 0.775 （95%CI： 0.699 — 0.851）， and 0.809 （95%CI： 0.752 — 0.866）， respectively， for predicting the risk of rebleeding at 6 weeks， 6 months， and 1 year. The calibration curve showed that the model systematically underestimated the probability of rebleeding at 6 weeks and 6 months， but its prediction for the probability of rebleeding at 1 year aligned well with the ideal curve. The decision curve analysis showed that the model provided a clear net clinical benefit for predicting rebleeding within 1 year. ConclusionThe model constructed based on ALBI score and PC/ST had good performance in predicting the risk of rebleeding within 1 year after endoscopic variceal ligation in liver cirrhosis patients with EVB.

ObjectiveTo explore the possible mechanisms of Modified Shoutai Pill （寿胎丸加味方， MSP） in treating polycystic ovary syndrome （PCOS） with hyperandrogenism， insulin resistance， and miscarriage， focusing on inflammatory response and endometrial receptivity. MethodsThirty female SPF-grade SD rats with regular estrous cycles and in proestrus， and 15 male SPF-grade SD rats were housed together in a 2∶1 ratio at 18：00. At 8：00 next morning， rats showing abundant sperm and vaginal plugs were considered pregnant on the day 0.5. The 30 pregnant rats were randomly divided into three groups， normal group， model group， and MSP group， with 10 rats in each group. From day 0.5 to day 13.5 of pregnancy， the MSP group was given 26.6 g/（kg·d） of the MSP via gavage twice a day for 14 consecutive days. The normal group and the model group received 4 ml of normal saline daily. From day 7.5 to day 13.5 of pregnancy， the rats in the model group and MSP group were intraperitoneally injected with dihydrotestosterone （DHT） and insulin （INS） for 7 consecutive days to establish a PCOS model with hyperandrogenism， insulin resistance， and miscarriage. On day 13.5 of pregnancy， an oral glucose tolerance test （OGTT） was performed to measure blood glucose levels at 0， 30， 60， 90， and 120 minutes. On day 14.5， serum level of progesterone （P₄）， estradiol （E₂）， fasting insulin （FINS）， interleukin-6 （IL-6）， and tumor necrosis factor-alpha （TNF-α） were measured by ELISA. The insulin resistance index （HOMA-IR） was calculated. Embryo implantation， miscarriage rate， and average number of live fetuses were observed. Uterine tissue pathology was examined by HE staining， and mRNA expression of Il-6， Tnf-α， leukemia inhibitory factor （Lif）， homeobox gene 10 （Hoxa10）， prolactin family 8 subfamily A member 2 （Prl8a2）， and insulin-like growth factor-binding protein 1 （Igfbp1） in the uterine tissue was detected by qRT-PCR. ResultsCompared with the normal group， the model group had significantly higher blood glucose level at 0， 30， 60， 90， and 120 minutes， increased miscarriage rate， elevated HOMA-IR， decreased average number of live fetuses， lower level of P₄ and E₂， higher level of IL-6， TNF-α， and FINS， and higher mRNA expression of Il-6 and Tnf-α in the uterine tissue. The mRNA expression of Lif， Hoxa10， and Prl8a2 was reduced （P＜0.05 or P＜0.01）. The uterus had a dark red color， visible areas of bleeding， fewer embryos with developmental abnormalities， and increased placental necrosis. Pathological examination revealed thrombus in the decidual layer， unclear decidual cell morphology， loose arrangement， scattered distribution， edema degeneration in the cytoplasm， and nuclear shrinkage or disappearance， with extensive infiltration of inflammatory cells. In contrast， compared with the model group， the MSP group showed significantly lower blood glucose level at 0， 30， 60， 90， and 120 min， reduced miscarriage rate， lower HOMA-IR， increased number of live fetuses， higher level of P₄ and E₂， and lower level of IL-6， TNF-α， and FINS. The mRNA expression of Il-6 and Tnf-α in the uterine tissue was lower， while the expression of Lif， Hoxa10， and Prl8a2 mRNA was higher （P＜0.05 or P＜0.01）. There was significant improvement in uterine and embryo conditions， as well as in uterine tissue pathology. ConclusionThe MSP can reduce the miscarriage rate in a PCOS model with hyperandrogenism， insulin resistance， and miscarriage. Its mechanism may involve inhibiting inflammation， improving endometrial receptivity， and restoring the defects in endometrial decidualization.

The NOD-like receptor protein 3 (NLRP3) inflammasome is essential in innate immune-mediated inflammation, with its overactivation implicated in various autoinflammatory, metabolic, and neurodegenerative diseases. Pharmacological inhibition of NLRP3 offers a promising treatment strategy for inflammatory conditions, although no medications targeting the NLRP3 inflammasome are currently available. This study demonstrates that clioquinol (CQ), a clinical drug with chelating properties, effectively inhibits NLRP3 activation, resulting in reduced cytokine secretion and cell pyroptosis in both human and mouse macrophages, with a half maximal inhibitory concentration (IC₅₀) of 0.478 μM. Additionally, CQ mitigates experimental acute peritonitis, gouty arthritis, sepsis, and colitis by lowering serum levels of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Mechanistically, CQ covalently binds to Arginine 335 (R335) in the NACHT domain, inhibiting NLRP3 inflammasome assembly and blocking the interaction between NLRP3 and its component protein. Collectively, this study identifies CQ as an effective natural NLRP3 inhibitor and a potential therapeutic agent for NLRP3-driven diseases.

OBJECTIVE: To explore the genetic etiology for a Chinese pedigree affected with X-linked cardiac valve dysplasia (CVDPX) and congenital chronic pseudo intestinal obstruction (CIIPX). METHODS: A pedigree presented at the First Hospital of Lanzhou University for CVDPX combined with CIIX was selected as the study subject. Whole exome sequencing (Trio-WES) was carried out, and the candidate variant was verified by Sanger sequencing. This study has been approved by the Medical Ethics Committee of the First Hospital of Lanzhou University (Ethics No. LDYYSZLLKH2024-15). RESULTS: Both the proband and his affected younger brother were found to harbor a hemizygous c.443A>G (p.Tyr148Cys) variant of the FLNA gene, for which their mother was heterozygous and their father was not a carrier, suggesting an X-linked recessive inheritance pattern. The variant was not recorded in the OMIM and ClinVar databases, and was determined to be likely pathogenic (PM2+PS4+PP2+PP3) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). The patients had presented with typical CVDPX/CIIPX phenotype, including multiple valve dysplasia and chronic pseudo intestinal obstruction, in addition with gallbladder wall edema and thickening. Bioinformatic analysis showed that the variant site is highly conserved, and multiple algorithms had predicted its pathogenicity. CONCLUSION This study confirmed the diagnosis of CVDPX/CIIX in a Chinese pedigree, expanded the phenotype spectrum of FLNA gene variants, and provided a basis for genetic counseling and prenatal diagnosis for the pedigree.
Adult ; Female ; Humans ; Male ; Exome Sequencing ; Filamins/genetics* ; Genetic Diseases, X-Linked/genetics* ; Heart Defects, Congenital/genetics* ; Heart Valve Diseases/genetics* ; Pedigree ; East Asian People/genetics*

OBJECTIVE: To explore the mechanism and clinical manifestations of a case with complex structural variations involving chromosomes 5, 7, and 14, and assess the value of Chromosome conformation-based karyotyping (C-MoKa) for its diagnosis. METHODS: Two half-sibs by the same father presented at the First Hospital of Lanzhou University in December 2024 for severe multi-system abnormalities were selected as study subjects. Peripheral blood samples from the their parents were subjected to conventional chromosomal karyotyping analysis. The father was further analyzed using C-MoKa, while both siblings underwent copy number variation sequencing (CNV-seq). This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: LDYYSZLLKH2025-05). RESULTS: Conventional karyotype analysis indicated that the father has a karyotype of 46,XY,add(5)(p15.3). CNV-seq identified multiple chromosomal abnormalities in both siblings, including duplications and deletions of chromosomes 14 and 5. C-MoKa analysis further revealed a complex chromosomal structural variation involving chromosomes 5, 7, and 14 in the father. These variations were closely associated with the severe phenotypes noted in both children. CONCLUSION Complex chromosomal structural variations can lead to multi-system abnormalities and significantly impact reproductive health. Compared to conventional karyotyping, the C-MoKa technique has shown significant advantage in identifying such complex rearrangements. The combined application of multiple techniques can improve the accuracy of diagnosis, enabling genetic counseling for carriers to reduce their risk for producing further affected offspring.
Female ; Humans ; Male ; China ; Chromosome Aberrations ; DNA Copy Number Variations/genetics* ; Karyotyping ; Pedigree ; East Asian People/genetics*

Lymphoma is a highly heterogeneous malignancy characterized by complex molecular regulatory mechanisms that result in significant differences in aggressiveness and prognosis across its subtypes.Gene copy number alteration(CNA)analysis,an emerging technology,has become a pivotal tool in the precision re-search and management of lymphoma.By detecting DNA deletions,amplifications,and chromosomal copy number changes,CNA analysis addresses the limitations of traditional cytogenetic techniques,enhances the ac-curacy of subtype classification,and aids in evaluating tumor heterogeneity and disease progression.This re-view provides a comprehensive summary of CNA detection methods and their applications in lymphoma,with a focus on recent advancements in the field.It offers a comparative analysis of CNA detection techniques and discusses their role in precision diagnosis,subtype classification,monitoring disease progression,predicting therapeutic resistance,and assessing prognosis.Additionally,the review explores the potential applications of CNA analysis in uncovering molecular regulatory mechanisms,optimizing therapeutic strategies,and impro-ving patient survival outcomes.