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.

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.

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.

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 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 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 explore the relationship between early fecal calprotectin (FC) level and the long-term efficacy of infliximab (IFX) in the treatment of Crohn′s disease (CD) and predictive the value.Methods:From January 2018 to December 2023, at the First Affiliated Hospital with Nanjing Medical University, the clinical data of patients with moderate-to-severe CD who received IFX as first-line therapy were retrospectively collected. The main outcomes were clinical and endoscopic remission at week 52 after IFX treatment, and the secondary outcome was clinical response at week 14 after IFX treatment. The predictive value of FC levels at week 0 (at baseline when first administered) and week 14 of treatment was evaluated for the clinical and endoscopic remission at week 52 after IFX treatment. Multivariate logistic regression was performed to investigate the factors predicting endoscopic remission. The optimal cutoff value was calculated, model was established, the data was divided into training set and validation set at a ratio of 7∶3 using the random number table method and the corresponding column chart was drawn. Receiver operating characteristic curve (ROC) and calibration curve were used to evaluate the discrimination and calibration of the model, respectively. Mann-Whitney U test was used for statistical comparison. Results:A total of 165 patients with CD were enrolled, of whom 150 cases (90.9%) achieved clinical response after induction therapy, and 15 cases (9.1%) were primary non-response. Among the 150 patients with clinical response, 112 cases (74.7%) achieved clinical remission at week 52 after treatment, while 38 cases (25.3%) did not achieve clinical remission. Endoscopic evaluation was performed at week 52 after treatment in 139 patients, of whom 54 cases (38.8%) achieved endoscopic remission and 85 cases (61.2%) did not. At week 14 of treatment, there was no statistically significant difference in FC level between the patients achieved and did not achieve clinical response (263.24 (93.96, 675.28) μg/g vs. 556.35 (245.77, 953.56) μg/g, P>0.05). At week 52 after treatment, the FC level of patients who achieved clinical remission was lower than that of patients did not achieve(103.20(44.11, 456.57) μg/g vs. 531.26(222.06, 998.40) μg/g) and the decreased value of FC at week 52 and week 0 after treatment of patients achieved clinical remission was more than that of patients did not achieve clinical remission (443.34 (82.25, 788.95) μg/g vs. 269.91 (-79.20, 522.54) μg/g), and the differences were statistically significant ( U=1 078.00, 2 677.00; P<0.001, =0.018). At week 52 after treatment, the FC level of patients achieved endoscopic remission was lower than that of patients did not achieve endoscopic remission (52.80(31.93, 83.47) μg/g vs. 506.18(217.44, 778.02) μg/g), and the decreased value of FC at week 52 and week 0 after treatment of patients achieved endoscopic remission was more than that of patients did not achieve endoscopic remission (428.85(140.20, 863.60) μg/g vs. 309.61(-62.37, 683.82) μg/g), and the differences were statistically significant ( U=500.00, 2 812.00; P<0.001, =0.025). The FC level at week 14 of treatment could predict the clinical and endoscopic remission at week 52 after treatment (area under the curve (AUC) =0.663, 0.773; 95% confidence interval (95% CI): 0.566 to 0.760, 0.694 to 0.852; P=0.006, <0.001). The optimal cutoff value of FC at week 14 of treatment for predicting endoscopic remission at week 52 after treatment was 246.13 μg/g, with a sensitivity of 0.741 and a specificity of 0.671. The results of multivariate logistic regression analysis revealed that FC ≤ 246.13 μg/g at week 14 of treatment ( OR=4.576, 95% CI: 2.021 to 10.363, P<0.001), baseline albumin ( OR=1.093, 95% CI: 1.006 to 1.188, P=0.035), and baseline platelet-to-lymphocyte ratio (PLR) ( OR=0.995, 95% CI: 0.990 to 1.000, P=0.046) were independent influencing factors of endoscopic remission at week 52 after treatment. A predictive model for endoscopic remission at week 52 after IFX treatment was established based on FC ≤ 246.13 μg/g at week 14 of treatment, baseline albumin and PLR. The results of ROC analysis showed that this model had good discriminative ability, with an AUC of 0.780 (95% CI: 0.700 to 0.878) in the validation set, with a sensitivity of 0.812 and a specificity of 0.760. The results of calibration curve analysis demonstrated that the average absolute error of the prediction model in the validation set was 0.038, and the consistency between the predicted probability and the actual probability was good. Conclusion:FC ≤ 246.13 g/g at week 14 of IFX treatment has good predictive value for endoscopic remission at week 52 after treatment in CD patients.

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.