OBJECTIVE To analyze the distribution characteristics of mirtazapine steady-state trough concentration and concentration-to-dose ratio （ C / D ）， and to investigate the influence of clinical and genetic factors on C / D . METHODS A retrospective study was conducted on hospitalized patients with depression who received mirtazapine treatment and underwent therapeutic drug monitoring at the First Hospital of Hebei Medical University from May 2022 to May 2025. The collected data included patients’ gender， age， body mass index， daily dose， steady-state trough concentration， smoking status， history of liver disease， drug type， concomitant medications， and CYP2D6 metabolic phenotype. The C / D was calculated. Spearman rank correlation was used to analyze the relationship between mirtazapine steady-state trough concentration and daily dose. Univariate analysis and multiple linear regression model were employed to screen the factors potentially influencing the C / D of mirtazapine. RESULTS A total of 226 patients were included. The daily dose of mirtazapine was 25.00 （24.82， 30.00） mg/d， the steady-state trough concentration was 44.46 （20.00， 70.00） ng/mL， and the C / D was 1.83 （1.00， 2.00） （ng·d）/（mL·mg）. Steady-state trough concentrations were within the reference range （30-80 ng/mL） in 121 patients （53.54%）， below the lower limit in 80 patients （35.40%）， and above the upper limit in 25 patients （11.06%）. A positive correlation was observed between mirtazapine steady-state trough concentration and daily dose （coefficient of determination was 0.320 8， P ＜0.001）. Gender， smoking status， and CYP2D6 metabolic phenotype were significantly associated with the mirtazapine C / D （ P ＜0.05）. CONCLUSIONS Significant interindividual variability exists in mirtazapine steady-state trough concentrations. Gender， smoking status， and CYP2D6 metabolic phenotype are identified as independent influencing factors for the mirtazapine C / D ， with higher C / D ratios observed in females， non-smokers， and intermediate metabolizers.

γδ T cells possess both innate and adaptive immune characteristics. Their antigen recognition is independent of major histocompatibility complex presentation， and they can directly recognize abnormal tumor metabolism， showing unique application potential in tumors with low immune infiltration. This paper systematically sorts out the biological characteristics and antitumor immune functions of γδ T cells， and mainly reviews the relevant mechanisms by which active ingredients of traditional Chinese medicine regulate γδ T cells to exert antitumor immune functions. Glycyrrhiza polysaccharide and Astragalus polysaccharide can enhance the antitumor immune function of γδ T cells by promoting the expression of various cytokines， regulating intestinal flora and alleviating immunosuppressive state. Quercetin and puerarin can strengthen γδ T cell-mediated tumor cell killing by regulating the proliferation of γδ T cells， the expression of cytotoxic effector molecules and related signaling pathways. Toosendanin can potentiate γδ T cell-induced tumor cell killing by down-regulating the expression of anti-apoptotic protein in tumor cells. Artesunate can boost γδ T cell-mediated antitumor immune responses by enhancing the effector function of γδ T cells and weakening tumor immune escape. Future research shall focus on exploring the synergistic effects and molecular mechanisms of the combined application of active ingredients of traditional Chinese medicine and γδ T cell immunotherapy， and identifying the key targets for γδ T cells to exert antitumor immune functions.

γδ T cells possess both innate and adaptive immune characteristics. Their antigen recognition is independent of major histocompatibility complex presentation， and they can directly recognize abnormal tumor metabolism， showing unique application potential in tumors with low immune infiltration. This paper systematically sorts out the biological characteristics and antitumor immune functions of γδ T cells， and mainly reviews the relevant mechanisms by which active ingredients of traditional Chinese medicine regulate γδ T cells to exert antitumor immune functions. Glycyrrhiza polysaccharide and Astragalus polysaccharide can enhance the antitumor immune function of γδ T cells by promoting the expression of various cytokines， regulating intestinal flora and alleviating immunosuppressive state. Quercetin and puerarin can strengthen γδ T cell-mediated tumor cell killing by regulating the proliferation of γδ T cells， the expression of cytotoxic effector molecules and related signaling pathways. Toosendanin can potentiate γδ T cell-induced tumor cell killing by down-regulating the expression of anti-apoptotic protein in tumor cells. Artesunate can boost γδ T cell-mediated antitumor immune responses by enhancing the effector function of γδ T cells and weakening tumor immune escape. Future research shall focus on exploring the synergistic effects and molecular mechanisms of the combined application of active ingredients of traditional Chinese medicine and γδ T cell immunotherapy， and identifying the key targets for γδ T cells to exert antitumor immune functions.

The clinical data of 2 pediatric patients with atypical hemolytic uremic syndrome (aHUS) who were admitted to the Department of Nephrology at the Children′s Hospital of Nanjing Medical University on July 2018 to June 2023 were retrospectively analyzed.Both patients had combined CFH and CD46 gene mutations.One patient, a 2-year-old boy, presented jaundice and darkened urine following mumps.The other patient, a 7-month-old girl and the younger sister of the boy, developed fever, cough, vomiting, and thrombocytopenia without any apparent cause.Laboratory tests revealed hemolytic anemia, thrombocytopenia, and acute kidney injury in both patients.The genetic test results revealed mutations in both CFH (c.3572C>T, p.Ser1191Leu) and CD46 genes (c.293C>T, p.Thr98Ile) in both patients.The patients′ mother is a heterozygous carrier of the CFH gene mutation, while their father is a heterozygous carrier of the CD46 gene mutation.Both parents exhibit normal phenotypes and are currently receiving regular infusions of Eculizumab.The pediatric aHUS caused by combined CFH and CD46 gene mutations is reported in this study for the first time in China.The clinical features of these patients are summarized and analyzed.

Objective To explore and identify the nutritional/inflammatory indicator with the highest predictive potential for overall survival(OS)in postoperative tumor patients so as to provide guidance for postoperative rehabilitation of tumor patients.Methods Data from 3 191 surgical patients were collected,including 15 nutritional/inflammatory indicators.The maximum selection rank statistic method was used to calculate the optimal cut-off values for continuous indicators.The Kaplan-Meier method was used to assess OS,and Cox proportional hazards models were used to analyze the association between the aforementioned 15 indicators and survival.The predictive value of these 15 indicators was evaluated with receiver operating characteristic(ROC)curves and C-index.Results Multivariate analysis showed that all 15 indicators were significantly associated with poorer OS in surgical patients(P＜0.05 for all).Time-dependent area under the curve(AUC)and C-index analysis indicated that 3 indicators with the highest predictive potential in OS in postoperative tumor patients were the nutritional risk index(NRI)(C-index:0.597),C-reactive protein-to-albumin ratio(CAR)(C-index:0.587),and C-reactive protein-to-lymphocyte ratio(CLR)(C-index:0.587).The optimal cut-off value for NRI was determined to be 104.31(i.e.,NRI＜104.31 suggests malnutrition)with the maximum selection rank statistic method,the optimal cut-off value for CAR to be 0.05(i.e.,CAR≥0.05 suggests a strong inflammatory response,often accompanied by malnutrition),and the optimal cut-off value for CLR to be 1.18(i.e.,CLR≥1.18 suggests a strong inflammatory response).Subgroup analysis indicated that NRI,CAR,and CLR had good correlation with tumor staging,and there were significant differences between tumor node metastasis(TNM)Ⅲ/Ⅳ stage patients and TNM Ⅰ/Ⅱ stage patients when there was a strong inflammatory response or malnutrition.Conclusion In postoperative tumor patients,NRI,CLR,and CAR have high prognostic value.Combining these with the patient's clinical stage,it enables more precise guidance for clinical diagnosis and treatment strategies.

Objective To investigate the clinical characteristics of patients with chronic abacterial pros-tafitis(CAP),the CAP related factors were analyzed,and a risk prediction model for CAP were constructed and validated.Methods The clinical dataes of 252 suspected CAP patients admitted to the hospital from June 2022 to December 2024 were collected,the patients were divided into modeling set(ni=177)and validation set(n=75)by 7∶3 ratio.Based on the modeling set dataes,the Lasso was used to screen CAP related predictive factors,a logistic multiple factor model was used to analyze the independent influence factors of CAP and a risk prediction model was constructed.The validation set patient dataes were used to plot ROC and DCA and validate the predic-tion model.Results There were 86 cases of CAP in the modeling set,accounting for 48.59％;32 cases of CAP in the validation set,accounting for 42.67％.The Logistic multiple regression analysis showed that BMI,waist to hip ratio,abnormal elevation of IL-8,COX-2,and PGE2 in prostate fluid were independent influence factors of CAP(P＜0.05),a Nomogram column chart based on this was established.The ROC analysis showed that the sensitivity of the model for detecting CAP in the modeling and validation sets were 0.814 and 0.802,respectively,and the specificity were 0.673 and 0.703,respectively.The DCA analysis showed that the net benefit thresholds for model-ing and validation sets by column charts are 0.1～0.9 and 0.2～1.0,respectively.Conclusions The occurrence of CAP is related to the patient's BMI,waist to hip ratio,the levels of IL-8,COX-2,and PGE2 in prostate fluid.The predictive model established based on this is highly accurate and it can help for CAP screening.

Objective To investigate the application of cardiovascular magnetic resonance feature tracking(CMR-FT)in assessing myocardial strain in dilated cardiomyopathy(DCM)patients residing at high altitudes.Methods We retrospectively enrolled 29 DCM patients living at high altitudes(DCM-H),27 DCM patients living in a low-altitude plain environment(DCM-P),23 healthy volunteers living at a high altitude(HV-H),and 24 healthy volunteers living in a low-altitude plain environment(HV-P).All subjects underwent cine MRI scanning using a 3.0T rapid steady-state free precession sequence.The CMR images thus acquired were analyzed using cvi42,a post-processing software,to obtain left ventricular function and myocardial strain parameters.Results Compared with the HV-H group,the DCM-H group showed higher left ventricle end-diastolic volume(LVEDV)and left ventricle end-systolic volume(LVESV),and lower left ventricular ejection fraction(LVEF)and stroke volume(LVSV)(all P＜0.01).No significant difference was observed in cardiac function between the DCM-H and DCM-P groups(all P＞0.05).The absolute values of global radial strain(GRS),global circumferential strain(GCS),and global longitudinal strain(GLS)in the DCM-H group were lower than those in the HV-P group([14.5±6.5]％vs.[34.2±10.7]％,[-11.1±4.4]％vs.[-19.9±2.8]％,and[-7.7±3.2]％vs.[-13.6±4.1]％,respectively),with the differences being statistically significant(all P＜0.001).The DCM-H group had higher absolute GRS,GCS,and GCS values than the DCM-P group did([14.5±6.5]％vs.[7.0±2.7]％,[-11.1±4.4]％vs.[—5.4±2.2]％,and[—7.7±3.2]％vs.[—4.3±1.7]％,respectivley,all P＜0.01).Conclusion Myocardial strain in DCM patients living at a high altitude is lower than that in healthy volunteers living at a high altitude,but higher than that in DCM patients living in a low-altitude plain environment.CMR-FT can be used to quantitatively assess myocardial contractility in DCM patients living at a high altitude,showing promise for clinical application.

Objective To establish primary breast cancer cell lines from patient tissues and offer a new cancer cell model for basic research.Methods Breast cancer biopsy tissues were digested with typeⅡcollagenase and cultured in BCMI medium.When the cells proliferated rapidly,the medium was switched to DMEM.STR genotyping was per-formed to identify specific genetic markers of the four primary breast cancer cell lines.Colony expansion assays and sphere formation assays were conducted to analyze its tumorigenicity.Real-time PCR and Western blot experiments were used to analyze the expression of the epithelial-mesenchymal transition(EMT)molecule markers.Migration and invasion assays were performed to assess the metastatic potential of the primary breast cancer cells.Results We es?tablished four primary breast cancer cell lines:BC25#,BC51#,BC56#,and BC57#.These cell lines were cultured in DMEM medium,passaged multiple times and tagged with details about their clinical past.STR genotyping identified specific genetic markers for each of the four primary breast cancer cell lines.Clonogenic and sphere formation assays revealed that the four lines have a stronger tumor?forming capability compared to the classic breast cancer cell line T?47D.Real?time PCR and Western blot experiments showed that,compared to T?47D,the four primary breast cancer cell lines have decreased E?cadherin expression and increased vimentin expression.Migration and invasion assays indicated that BC25#had a higher metastatic potential than the traditional breast cancer cell line T?47D.Conclusions Four primary breast cancer cell lines,BC25#,BC51#,BC56#and BC57#are successfully estab?lished,which may act as new cancer cell model for laboratory research of breast cancer.

Objective To investigate the role of a novel human-specific long noncoding RNA(lncRNA),MEK6-AS1,and its potential molecular mechanism in improving the osteogenic differentiation of senescent mesenchymal stem cells(MSCs).Methods An in vitro human MSCs replicative senescence model was established by sequen-tial passaging,and then senescence was identified by β staining and senescence-related gene expression.RT-qPCR was used to detect the expression of MEK6-AS1 during senescence and osteogenic differentiation of human MSCs(hMSCs);Lentiviral knockdown technology was used to regulate the expression of MEK6-AS1 in the MSCs replicative senescence model.Transcriptome sequencing technology was utilized to analyze the effects of MEK6-AS1 on the transcriptome of hMSCs especially on genes and pathways related to osteogenic differentiation.The effect of MEK6-AS1 as an intervention target at osteogenic differentiation of human senescent hMSCs was evaluated with alkaline phosphatase staining microscopy.PCR technology was used to detect osteogenic gene expression levels in cells.Results With aging process,the osteogenic differentiation ability of hMSCs decreased significantly while the expression level of MEK6-AS1 was enhanced(P＜0.000 1).Knockdown of MEK6-AS1 significantly enhanced the osteogenic differentiation of MSCs by the up-regulating expression of osteogenic markers and increasing minerali-zation capacity(P＜0.001).Conclusions Knockdown of human-specific lncRNA MEK6-AS1 improves osteogenic differentiation of senescent MSCs,providing a new target and theoretical basis for the treatment of senescence-asso-ciated osteoporosis.

Objective:To investigate the effects and mechanisms of dendrobium officinale polysaccharides(DOP)on neural function and sleep in a rat model of ischemic stroke.Methods:Rats with ischemic stroke were modeled using middle cerebral artery occlusion(MCAO).The neurological function was assessed using the Longa scale.Sleep was monitored by electroencephalography.The hippocampal tissue damage was evaluated by TTC staining,HE staining,Nissl staining and TUNEL staining.The kits were used to detect reactive oxygen species(ROS),malondialdehyde(MDA),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),IL-1β,and IL-18 in the hippocampal tissue.West-ern blot analysis was conducted to detect the expression of microtubule-associated protein light chain 3(LC3)and Bec-lin1,NLRP3,apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),cleaved caspase-1(C-caspase-1),GSDMD-N-terminal domain(GSDMD-N),nuclear factor erythroid 2-related factor 2(Nrf2),and heme oxygenase-1(HO-1)in the hippocampal tissue.Results:DOP can improve sleep quality and neurological func-tion in rats with ischemic stroke,alleviate hippocampal tissue damage,inhibit oxidative stress and inflammation in the hippocampus,decrease the expression of Beclin1,NLRP3,ASC,C-caspase-1,GSDMD-N,cytosolic Nrf2 protein,and the LC3-Ⅱ/LC3-Ⅰ ratio in the hippocampus,while increasing the expression of HO-1 and nuclear Nrf2 protein.The Nrf2 inhibitor ML385 partially reversed the ameliorative effects of DOP.Conclusion:DOP may improve neurological function and sleep in rats with ischemic stroke by inhibiting autophagy and NLRP3 inflammasome-mediated pyroptosis through the activation of the Nrf2/HO-1 pathway,thereby alleviating oxidative stress and neuroinflammation.