Objective: To explore the impact of sleep quality, experience of childhood maltreatment, and their interaction on depressive symptoms among middle school students, so as to provide the reference for early intervention of depressive symptoms among middle school students. Methods: From September to December 2023, a questionnaire survey was conducted among 1 231 students from two secondary schools in Harbin, Heilongjiang Province by a convenient sampling method. The survey included general demographic information, Childhood Trauma Questionnaire Short Form, Pittsburgh Sleep Quality Index and Short Version of Center for Epidemiological Studies Depression Scale. The Chi square test was used to analyze the differences in depressive symptom, sleep quality and childhood maltreatment among students with different demographic characteristics. Correlation analysis was conducted using Logistic regression, and interaction analysis was performed by both additive and multiplicative interaction models. Results: The detection rate of depressive symptoms among middle school students was 22.7%, and the rate for high school students (35.2%) was significantly higher than that for middle school students (17.0%) ( χ 2=50.35, P <0.01). The detection rates of depressive symptoms among middle school students with a history of childhood maltreatment and poor sleep quality were 45.8% and 44.0%, respectively. Multivariate Logistic regression analysis showed that compared to students without a history of childhood maltreatment, students with a history of childhood maltreatment had a higher risk of depressive symptoms ( OR =4.49，95% CI =3.31~ 6.09 , P <0.01);students with poor sleep quality had a higher risk of depressive symptoms than students with good sleep quality ( OR = 5.99，95% CI =4.37~8.22, P <0.01).The interaction results showed that the presence of childhood maltreatment and poor sleep quality had an additive interaction on the occurrence of depression in middle school students. Compared with students without childhood maltreatment and having good sleep quality, students with childhood maltreatment and poor sleep quality had a 22.49 times higher risk of developing depression ( OR =22.49，95% CI =14.22~35.59, P <0.01). Conclusion Depressive symptoms among middle school students are associated with childhood maltreatment and poor sleep quality, and there is an additive interaction between childhood maltreatment and poor sleep quality on the impact of depressive symptoms.

Artificial intelligence （AI） and population pharmacokinetics （PPK） technologies have demonstrated significant potential in the personalized medication of immunosuppressants after organ transplantation, enabling precise prediction of drug dosages. This article provides a comprehensive review of the application status of AI and PPK in the individualized administration of immunosuppressants after organ transplantation， focuses on monitoring blood drug concentration， predicting efficacy/adverse reactions， and establishing individualized dosing models for organ transplant recipients after immunosuppressant administration， and analyzes and compares the application characteristics of different methods in different organ transplant patients as well as the integration and future development of AI and PPK technologies. AI and PPK technologies can not only significantly reduce the dependence on human resources， but also greatly improve the level of individualized treatment of immunosuppressants after organ transplantation， and reduce the discomfort and burden caused by frequent blood concentration monitoring to patients.

Glucagon-like peptide-1 （GLP-1） receptor agonists are a novel class of antidiabetic drugs that also possess lipid- lowering and cardiovascular protective effects， with liraglutide and semaglutide being their representative medications. Based on a systematic literature search， this review summarizes the lipid-lowering mechanisms by which liraglutide and semaglutide exert direct effects on the liver and kidney （regulating autophagy， key lipid metabolism pathways， reverse cholesterol transport， etc.）， direct actions on adipose tissue （affecting adipocyte proliferation and differentiation， expression of lipid metabolism proteins， and gene transcription）， activation of sympathetic pathways through the central nervous system， and modulation of the gut microbiota. Additionally， it summarizes the clinical evidence of their lipid-lowering effects in populations with type 2 diabetes mellitus， overweight individuals， and others. These findings indicate that GLP-1 receptor agonists exert lipid-lowering effects by acting on multiple tissues or systems， providing crucial evidence for further elucidating the molecular mechanisms of these drugs in lipid regulation and exploring potential new ideas for their clinical applications.

Objective:To investigate the clinical features and prognosis of prolonged cytopenia (PC) in patients with large B-cell lymphoma (LBCL) undergoing anti-CD19 chimeric antigen receptor T (CAR-T) cell therapy.Methods:A retrospective case series study was conducted on LBCL patients who received CAR-T cell therapy with a survival time of over one month at the Hematology Department of Peking Union Medical College Hospital from March 2019 to December 2023. Statistical analyses were performed on hematologic changes at 1, 3, 6, and 12 months post-CAR-T infusion, as well as on the progression-free survival (PFS) and post-treatment adverse events, including infections. Patients were categorized into the PC and non-PC groups based on the occurrence of cytopenia at 90 days post-infusion. Differences between groups were compared, and univariate logistic regression analysis was used to identify risk factors.Results:The median age of 27 LBCL patients receiving CAR-T cell therapy was 58 years (range 27-69 years), with 18 males. Among the 27 LBCL patients who received CAR-T cell therapy, PC was observed in 19 patients (70.4%), with instances of neutropenia (48.1%, 13 cases), anemia (37.0%, 10 cases), and thrombocytopenia (22.2%, 6 cases). Univariate logistic regression analysis revealed that prior chemotherapy sensitivity ( OR=18.00, 95% CI 1.56-207.45, P=0.020) and bone marrow suppression ( OR=18.00, 95% CI 1.38-235.69, P=0.028) were associated with PC. The median follow-up time was 13.5 months. The PC group exhibited a higher risk of infection within 3 months (9/19 vs. 1/8) and a shorter mean PFS (19.3 months vs. 24.4 months), although the difference was not statistically significant (both P>0.05). Conclusions:PC is common following CAR-T cell therapy and is associated with an increased risk of infection and poorer prognosis. Prior treatment sensitivity and bone marrow suppression may serve as indicators of PC.

This paper summarises the nursing experiences with a lung cancer patient who suffered Grade 4 mixed hepatotoxicity characterised with cholestasis.Summarised key care measures include close observation of liver biochemical indexes,timely and safe administration of immunosuppressants,implementation of skincare procedure,prevention of opportunistic infections,individualised exercises,nutrition care,sleep care and psychological care.The patient was discharged with oral immune inhibitors after 29 days of hospitalisation when the hepatotoxicity had been improved and down to Grade 1.In the second month of follow-up,the patient had a well-recovered liver function.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective:To investigate the efficacy and safety of protein A immunoadsorption (PAIA) combined with rituximab (RTX) in highly sensitized patients who underwent haplo-hematopoietic stem cell transplantation (haplo-HSCT) .Methods:The clinical data of 56 highly sensitized patients treated with PAIA and RTX before haplo-HSCT at the First Affiliated Hospital of Soochow University and Soochow Hopes Hematonosis Hospital between March 2021 and June 2023 were retrospectively analyzed. The number of human leukocyte antigen (HLA) antibody types and the mean fluorescence intensity (MFI), humoral immunity, adverse reactions during adsorption, and survival within 100 days before and after adsorption were measured.Results:After receiving the PAIA treatment, the median MFI of patients containing only HLA Ⅰ antibodies decreased from 7 859 (3 209-12 444) to 3 719 (0-8 275) ( P<0.001), and the median MFI of HLA Ⅰ+Ⅱ antibodies decreased from 5 476 (1 977-12 382) to 3 714 (0-11 074) ( P=0.035). The median MFI of patients with positive anti-donor-specific antibodies decreased from 8 779 (2 697-18 659) to 4 524 (0–15 989) ( P<0.001). The number of HLA-A, B, C, DR, and DQ antibodies in all patients decreased after the PAIA treatment, and the differences were statistically significant (A, B, C, DR: P<0.001, DQ: P<0.01). The humoral immune monitoring before and after the PAIA treatment showed a significant decrease in the number of IgG and complement C3 ( P<0.001 and P=0.002, respectively). Forty-four patients underwent HLA antibody monitoring after transplantation, and the overall MFI and number of antibody types decreased. However, five patients developed new antibodies with low MFI, and nine patients continued to have high MFI. The overall survival, disease-free survival, non-recurrent mortality, and cumulative recurrence rates at 100 days post-transplantation were 83.8%, 80.2%, 16.1%, and 4.5%, respectively. Conclusions:The combination of PAIA and RTX has a certain therapeutic effect and good safety in the desensitization treatment of highly sensitive patients before haplo-HSCT.

Objective To investigate the protective effect of herba artemisiae scopariae extract on multidrug resistance protein 3(MDR3)gene mutation-induced neonatal parenteral nutrition-associated cholestasis(PNAC)and its possible mechanism.Methods ①Human primary hepatocytes were treated with cell culture in vitro,CRISPR/Cas9 lentivirus infection and MDR3 mutant gene lead-in.The levels of hepatic and biliary biochemical indexes[alanine transaminase(ALT),aspartate transaminase(AST),total bilirubin(TBil),direct bilirubin(DBil),indirect bilirubin(IBil),total bile acid(TBA)]in the supernatant of hepatocytes before and after 16,32,48 hours were compared to determine the time required for fatty acid induction of PNAC hepatocyte model with MDR3 gene mutation.② Human primary hepatocytes were divided into blank control group,MDR3 gene wild type group,MDR3 gene mutation group,and herba artemisiae scopariae extract intervention group according to random number table method.The blank control group was treated with culture medium only,the MDR3 gene wild type group was infected with lentivirus and mixed with wild type MDR3 gene and culture medium,the MDR3 gene mutation group was infected with lentivirus and cultured in culture medium with the mutant genes lead-in of LV-MDR3KI(c.485T>A,c.2793insA,c.1031G>A,c.3347G>A)mutation,while the MDR3 mutant gene was lead-in by lentivirus infection and cultured in culture medium,and then pretreated with 100 g/L herba artemisiae scopariae extract in the herba artemisiae scopariae extract intervention group,then the four groups of hepatocytes were induced with 1%fat emulsion,and the treatment time was the time needed to construct the PNAC hepatocytes model with MDR3 gene mutation.The levels of ALT,AST,TBil,DBil,IBil and TBA in the supernatant of hepatocytes were measured by enzyme-linked immunosorbent assay(ELISA).The mRNA expression abundance of adenosine triphosphate binding cassette proteins(ABCB4,ABCB11,ABCC2,ABCC3,ABCC4)encoding MDR3,bile salt export pump(BSEP),multidrug resistance associated protein(MRP)2-4,and tumor necrosis factor-α(TNF-α)genes were detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).Results Compared to the blank control group and MDR3 gene wild type group,there was no significant difference in the levels of ALT,AST,TBil,DBil,IBil,TBA in the supernatant of MDR3 gene mutant group before and 16 hours after induction with 1%fat emulsion,however after treated with 1%fat emulsion for 32 hours and 48 hours,the levels of ALT,AST,TBil,DBil,IBil,TBA in the supernatant of MDR3 mutant hepatocytes were significantly increased(P<0.05),consequently the time required for fatty acid induction of PNAC hepatocyte model was 32 hours.At 32 hours after treatment with fat emulsion,the levels of ALT,AST,TBil,DBil,TBA in the supernatant of hepatocytes in the herba artemisiae scopariae extract intervention group were significantly decreased[ALT(ng/L):148.3±2.3 vs.164.9±7.0,AST(ng/L):2767.4±78.8 vs.3239.4±107.1,TBil(μmol/L):7.6±0.2 vs.13.6±0.3,DBil(μmol/L):1.8±0.1 vs.5.7±0.2,TBA(μmol/L):3.4±0.2 vs.6.7±0.1,all P<0.05].The ABCB4,ABCC2,ABCC3,ABCC4 mRNA expression of MDR3,MRP2,MRP3,MRP4 in the blank control group,MDR3 wild type group,MDR3 gene mutation group and the herba artemisiae scopariae extract intervention group had no significant difference.The expression of TNF gene mRNA was highly expressed in MDR3 gene mutation group(2-??Ct:1.258±0.200 vs.1.001±0.052),and was low expressed in the herba artemisiae scopariae extract intervention group(2-??Ct:0.387±0.247 vs.1.258±0.200),and there was a significant difference between the two groups(both P<0.05).Compared to the MDR3 gene mutation group,the ABCB11 gene encoding BSEP mRNA expression in the herba artemisiae scopariae extract intervention group was significantly increased(2-??Ct:2.955±0.479 vs.1.333±0.529,P<0.05).Conclusion The herba artemisiae scopariae extract has a protective effect on PNAC induced by MDR3 gene mutation,which may be related to antagonizing inflammatory reaction,decreasing the expression of TNF mRNA and improving the expression of ABCB11 gene encoding BSEP.

ObjectiveTo prepare a rat model of heart failure after myocardial infarction by ligation of the anterior descending branch of the left coronary artery， and to observe the effect of Shenfu Yixin granules on the mitochondrial dynamics of rats with heart failure. MethodFifty SD male rats were randomly taken ten as the sham operation group and the rest as modeling group. The rat model of heart failure after myocardial infarction was prepared by ligation of anterior descending branch of left coronary artery. According to the left ventricular ejection fraction（LVEF） on the 28^th day after operation， the model rats were randomly divided into the model group， Shenfu Yixin granule low-dose and high-dose groups（3.011， 15.055 g·kg^-1） and sacubitril valsartan sodium group（20.83 mg·kg^-1）. Each administration group was gavaged daily with the corresponding dose of drug solution， while the sham operation group and model group were given the same amount of normal saline once a day for 28 days， with 6 rats in each group. Ultrasound was used to detect the cardiac function parameters， rat heart mass and body mass were weighed to calculate the cardiac mass index， enzyme linked immunosorbent assay（ELISA） was used to detect serum brain natriuretic peptide（BNP） and soluble growth stimulation expressed gene 2 protein（sST2） levels. Hematoxylin-eosin（HE） staining was used to observe the pathological morphology of the myocardium. Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） and Western blot were used to detect the mRNA and protein expression of mitochondrial fusion protein 1/2（Mfn1/2）， optic atrophy protein 1（Opa1）， dynamin-related protein 1（Drp1） and fission protein 1（Fis1）. ResultCompared with the sham operation group， the mRNA and protein expression of LVEF， Mfn1， Mfn2， Opal in the model group decreased（P<0.05）， while BNP， sST2， cardiac mass index， Drp1， Fis1 mRNA and protein levels increased（P<0.05）. Compared with the model group， the expression of LVEF， Mfn1， Mfn2， Opal mRNA and protein increased in Shenfu Yixin granule high-dose and sacubitril valsartan sodium groups（P<0.05）， while BNP， sST2， cardiac mass index， Drp1， Fis1 mRNA and protein levels decreased（P<0.05）. Pathological observation showed that compared with the sham operation group， the model group had disordered arrangement of myocardial cells， inflammatory cell infiltration and myocardial fibrosis. Compared with the model group， the degree of inflammatory cell infiltration， myocardial or interstitial fibrosis was improved and alleviated in all administered groups. ConclusionShenfu Yixin granules can resist heart failure， reduce cardiac mass index， decrease BNP and sST2 contents， and improve cardiac function. Its mechanism may be related to the adjustment of mitochondrial dynamics.

Objective:To evaluate the clinical efficacy of ultrasound-guided superior laryngeal nerve block combined with cricothyroid membrane puncture for awake tracheal intubation in difficult airways.Methods:A total of 80 patients scheduled for general anesthesia surgery owing to difficult airways at Marine Police Corps Hospital of Chinese People's Armed Police Force from August 2019 to February 2023 were included in this prospective study. These patients were randomly divided into a control group and an observation group ( n = 40 per group). Both groups of patients underwent fiberoptic bronchoscope-guided awake tracheal intubation through the nasal route. Before intubation, the control group received surface anesthesia combined with cricothyroid membrane puncture anesthesia, while the observation group received superior laryngeal nerve block combined with cricothyroid membrane puncture anesthesia. During the intubation process, hemodynamic indicators of the patients were monitored, the duration of the intubation operation was recorded, and the degree of sedation and cough response was evaluated. Before and after intubation, the levels of serum stress response factors were determined, and the satisfaction level of patients with the intubation operation was investigated. Results:At the time points T1 (immediately after the tracheal tube enters the glottis) and T2 (after the tracheal tube enters the trachea), the heart rate in the observation group was (84.08 ± 8.25) times/minute and (82.64 ± 7.81) times/minute, respectively, and the mean arterial pressure in the observation group was (92.57 ± 8.32) mmHg (1 mmHg = 0.133 kPa) and (103.27 ± 9.16) mmHg, respectively, which were significantly lower compared with those in the control group ( t = 5.92-12.56, all P < 0.001). At T1 and T2, there was no significant difference in blood oxygen saturation (SpO 2) between the observation and control groups ( t = 0.34-0.43, P = 0.652-0.726). The duration of the intubation operation in the observation group was (8.96 ± 1.15) minutes, which was significantly shorter than (11.47 ± 1.39) minutes in the control group ( t = 6.84, P < 0.001). The Ramsay sedation score during intubation in the observation group was 3 (2,3) points, which was significantly higher than 2 (1,3) points in the control group ( Z = 9.26, P < 0.001). The cough response score in the observation group was 1 (0,1) point, which was significantly lower than 1 (0, 2) points in the control group ( Z = 4.37, P < 0.001). The serum levels of stress response factors norepinephrine and adrenaline in the observation group were significantly lower than those in the control group ( t = 14.58-25.94, both P < 0.05). The overall patient satisfaction in the observation group was 97.50%, which was significantly higher than that in the control group ( χ2 = 4.51, P = 0.034). Conclusion:Superior laryngeal nerve block combined with cricothyroid membrane puncture can be used for anesthetic management of awake nasal tracheal intubation in difficult airways. This combined approach can improve patient hemodynamic stability and sedation, shorten the duration of intubation, reduce stress responses during intubation, and enhance patient satisfaction.