OBJECTIVE To investigate a dynamic monitoring of drug consumption （DMDC） model based on the seasonal Mann-Kendall trend test， aiming to provide scientific evidence for the efficient and macroscopic monitoring of drug use. METHODS A monitoring list of key outpatient drugs was established based on the top 20% of drugs ranked by sales volume in the outpatient pharmacy in October 2024. A DMDC model based on the Mann-Kendall trend test was constructed using the monthly usage data of key outpatient drugs from November 2021 to October 2024， aiming to eliminate the impact of seasonal fluctuations and analyze the temporal trends in drug consumption. Taking mucolytic expectorants， triazole derivatives for dermatophytosis， and single-agent hydroxymethylglutaryl coenzyme A （HMG-CoA） reductase inhibitors as examples， the monitoring effectiveness of the DMDC model was demonstrated， and its performance was compared with that achieved by the traditional sequential growth rate ranking method. RESULTS A total of 215 drug varieties were included in the monitoring list， and DMDC models were successfully established for all of them. Among these， 119 showed a significant increasing trend （P＜0.05， S′＞0）. The model successfully monitored the monthly consumption of mucolytic expectorants， triazole derivatives for dermatophytosis， and single- agent HMG-CoA reductase inhibitors. The precision and recall rates of the DMDC model for identifying abnormal drug use were 60.7% and 85.0%， respectively， both significantly higher than those of the sequential growth rate ranking method （8.3% and 15.0%， respectively） （χ2＝20.114， P＜0.001； χ2＝19.600， P＜0.001）. CONCLUSIONS DMDC model based on the seasonal Mann-Kendall trend test can effectively identify long-term trends in drug consumption， eliminate seasonal interference， enhance monitoring accuracy and management efficiency， and is suitable for the dynamic monitoring of drug consumption.

OBJECTIVE To provide scientific evidence and practical references for refined antimicrobial stewardship in multi- branch medical institutions. METHODS Data of antibiotic use density （AUD） of inpatients as well as physician-level case mix index （CMI） were collected from the Liji Road main campus and Panlongcheng branch campus of our hospital from August 2023 to March 2026. The two-factor decomposition method was adopted to decompose total AUD variation into a level effect and structural effect. Grey relational analysis （GRA） was performed to quantify the correlation degree between ward CMI， physician CMI and physician AUD， so as to identify wards and physicians requiring targeted key intervention in different campuses. A refined antimicrobial management framework for multi-branch hospitals was constructed and implemented based on the above analytical results. An interrupted time series （ITS） model incorporating seasonal dummy variables was applied. The research period was divided into pre-intervention stage （August 2023 to March 2024） and post-intervention stage （April 2024 to March 2026）. The temporal changing trends of AUD in two campuses were compared to evaluate management efficacy. RESULTS Driving factors for AUD variation presented significant heterogeneity between the two campuses. AUD variation in the main campus was dominated by level effect， while AUD variation in the branch campus was jointly affected by structural effect and level effect. The grey relational degrees of ward CMI and physician CMI with physician AUD were 0.901 and 0.882， respectively. After refined management implementation， AUD decreased by 7.48 DDDs/（100 bed·days） and 20.54 DDDs/（100 bed·days） in the main campus and branch campus， respectively； the rising trends of AUD in both campuses reversed to declining trends after intervention. CONCLUSIONS Driving factors of AUD variation under the multi-branch hospital model show obvious inter-campus heterogeneity. CMI is highly correlated with AUD. The refined management system developed via AUD attribution decomposition and CMI correlation analysis matches the differentiated clinical characteristics of multi- branch hospitals and effectively improves the precision of antimicrobial stewardship.

Non-alcoholic fatty liver disease(NAFLD)is a chronic liver disease caused by excessive lipid accumulation in the liver.Its incidence rate is increasing year by year and has become an increasingly serious public healthy problem.The pathogenesis of NAFLD is complex and has not been fully clarified at present.It is mainly related to multiple factors such as genetics,metabolism,intestinal flora and immune response.In order to explore the medication rules and mechanism of action of traditional Chinese medicine(TCM)in the treatment of NAFLD,and to provide references for the treatment of NAFLD with TCM and the research and development of new drugs,this article summarizes the TCM pathogenesis of NAFLD(such as"phlegm and blood stasis interlacing","liver depression and spleen deficiency",etc.)and modern etiology and pathogenesis(such as insulin resistance,lipid disorder,mitochondrial dysfunction,oxidative stress,etc.).The clinical research and experimental data at home and abroad in recent years were integrated to analyze the pathological process of NAFLD intervention by TCM through multiple targets,including improving insulin resistance and lipid metabolism disorders,inhibiting oxidative stress and mitochondrial dysfunction,etc.TCM has shown unique advantages in the prevention and treatment of NAFLD.However,the depth of its mechanism analysis and the level of clinical research still need to be improved.In the future,it is necessary to deepen the mechanism research by combining multi-omics technology to accelerate the modernization development of TCM.

Objective:To compare the efficacy of Union Plate combined with robotic placement of infra-acetabular and posterior column screws and common reconstruction plate combined with freehand placement of infra-acetabular and posterior column screws in the treatment of complex acetabular fractures.Methods:The data of 42 patients with complex acetabular fractures treated in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from June 2020 to June 2023 were retrospectively analyzed. Among them, 22 patients were treated with Union Plate combined with robotic placement of posterior column screws and infra-acetabular screws (Union Plate robot group). 20 cases were treated with common reconstruction plate combined with posterior column screw and infra-acetabular screw fixation by hand (reconstruction plate freehand group). The Union Plate robot group included 16 males and 6 females, aged 43.7±11.6 years (range, 24-67 years). Letournel-Judet classification: 14 cases of double-column fractures, 5 cases of anterior column with posterior semi-transverse fractures, 3 cases of "T" -shaped fractures. There were 15 males and 5 females in the reconstruction plate freehand group, aged 42.9±12.0 years (range, 22-66 years). Letournel-Judet classification: 15 cases of double-column fractures, 3 cases of anterior column with posterior semi-transverse fractures, 2 cases of "T" -shaped fractures. The operative time, intraoperative blood loss, intraoperative fluoroscopy times, frame screw placement time, fracture healing time, perfect frame screw placement rate (grade 0 rate) assessed according to the Lonstein criteria, reduction quality assessed according to the Matta criteria, the modified Merle d'Aubign-Postel score and postoperative complications were compared between the two groups.Results:All 42 patients were followed up for 10 to 30 months, with an average of 13 months. The fracture healing time was 3.4±0.4 months in the Union Plate robot group and 3.6±0.4 months in the reconstruction plate freehand group, with no statistical significance ( t=2.179, P=0.035). The operative time and intraoperative blood loss of the Union Plate robot group were 138.3±30.7 min and 735.7±159.8 ml, respectively, which were lower than 163.9±48.7 min and 843.5±181.1 ml in the reconstruction plate freehand group. The differences were statistically significant ( P<0.05). The time and intraoperative fluoroscopy times of the Union Plate robot group were 19.9±3.2 min and 17.1±4.9 times, respectively, which were less than 42.5±6.7 min and 45.4±4.9 times of the reconstruction plate freehand group, and the differences were statistically significant ( P<0.05). According to the Lonstein evaluation, there were 42 cases of class 0 and 2 cases of class I in the Union Plate robot group, and the perfect frame screw placement rate was 96%(42/44). There were 30 cases of grade 0, 8 cases of grade I and 2 cases of grade II in the reconstruction plate freehand group, and the perfect frame screw placement rate was 75%(30/40). There was significant difference between the two groups (χ 2=7.426, P=0.024). According to the Matta criteria, 15 cases of Union Plate robot group were excellent, 4 cases were good, and 3 cases were poor, with an excellent and good rate of 86%(19/22). In the reconstruction plate free hand group, 13 cases were excellent, 4 cases were good, and 3 cases were poor, with an excellent and good rate of 85%(17/20). There was no significant difference between the two groups (χ 2=0.048, P=0.976). At the last follow-up visit, the modified Merle d'Aubign-Postel score of the Union Plate robot group was 16.9±1.7 points and that of the reconstruction plate freehand group was 16.5±2.2 points, with no statistical significance ( t=0.593, P=0.557). In the Union Plate robot group, wound fat liquefaction and lateral femoral cutaneous nerve injury occurred in 1 case, the complication rate was 9%(2/22). There were 4 cases of fat liquefaction, 1 case of lateral femoral cutaneous nerve injury, and 1 case of traumatic hip arthritis in the reconstruction plate freehand group. The complication rate was 30%(6/20), and the difference in complication rate was not statistically significant (χ 2=1.769, P=0.183). Conclusions:The clinical efficacy of Union Plate combined with robotic placement of posterior column screws and infra-acetabular screws in the treatment of complex acetabular fractures is comparable to that of reconstruction plate combined with freehand placement of posterior column screws and infra-acetabular screws. However, the use of Union Plate combined with robotic placement of frame screws can shorten the operative time and the time of frame screw placement. The amount of intraoperative blood loss and intraoperative fluoroscopy times were reduced, and the accuracy of frame screw placement was higher.

Objective"Lie flat"has recently become a buzz word describing a specific psychological state in some individuals.However,its psychological meaning and mechanisms remain unclear.Lack of motivation under certain conditions may be one of the key psychological characteristics of this condition.Methods Sixteen male SD rats were randomly assigned to two food-restriction levels(90%and 80%of baseline weight,respectively),and subjected to a sucrose-pellet self-administration task.The establishment of the model is divided into three stages.The rats were trained to self-administer sucrose pellets in a high-reward learning stage and in a low-reward learning stage.We then assessed"lie flat"behavior in a preference-test stage,in which rats could choose between high-reward-and low-reward-paired nose-pokes in a discrete choice procedure.Results Combining self-feeding training with Western blot,the results showed that:(1)rats showed significantly decreased nose-poke behavior for low-reward,i.e."lie flat"behavior,but not for high-reward,when≥90%of the maximal reward was obtained in the high-reward task and the effort(X)in the low-reward task increased to the breaking point.(2)Dopamine D1R expression in the NAc was significantly higher in the"lie flat"group compared with the"not lie flat"rats,while D2R expression was similar in both groups.Conclusions Rats can show"lie flat"behavior,and up-regulation of D1R expression in the NAc may be a key part of the molecular basis responsible for this motivation deficiency in"lie flat"behavior.These results extend our understanding of"lie flat"behavior,and provide a new paradigm for the study of its mechanism.

Objective"Lie flat"has recently become a buzz word describing a specific psychological state in some individuals.However,its psychological meaning and mechanisms remain unclear.Lack of motivation under certain conditions may be one of the key psychological characteristics of this condition.Methods Sixteen male SD rats were randomly assigned to two food-restriction levels(90%and 80%of baseline weight,respectively),and subjected to a sucrose-pellet self-administration task.The establishment of the model is divided into three stages.The rats were trained to self-administer sucrose pellets in a high-reward learning stage and in a low-reward learning stage.We then assessed"lie flat"behavior in a preference-test stage,in which rats could choose between high-reward-and low-reward-paired nose-pokes in a discrete choice procedure.Results Combining self-feeding training with Western blot,the results showed that:(1)rats showed significantly decreased nose-poke behavior for low-reward,i.e."lie flat"behavior,but not for high-reward,when≥90%of the maximal reward was obtained in the high-reward task and the effort(X)in the low-reward task increased to the breaking point.(2)Dopamine D1R expression in the NAc was significantly higher in the"lie flat"group compared with the"not lie flat"rats,while D2R expression was similar in both groups.Conclusions Rats can show"lie flat"behavior,and up-regulation of D1R expression in the NAc may be a key part of the molecular basis responsible for this motivation deficiency in"lie flat"behavior.These results extend our understanding of"lie flat"behavior,and provide a new paradigm for the study of its mechanism.

Objective To investigate the effects of Gandou Fumu Decoction on liver fibrosis,iron metabolism,and ferroptosis in patients with hepatolenticular degeneration(Wilson disease,WD).Methods Seventy-eight hospitalized patients with WD characterized by kidney and liver deficiency,with phlegm and blood stasis,from the Department of Neurology,the First Affiliated Hospital of Anhui University of Chinese Medicine,were randomly assigned to two groups using a random number table method.The control group(n=39)received sodium dimercaptosulfonate in combination with a low-copper and high-protein diet.The observation group(n=39)received the same treatment as the control group,with the addition of Gandou Fumu Decoction(one dose per day,taken twice daily,in the morning and evening).Both groups underwent six treatment cycles,each lasting eight days.Ultrasonographic parameters,including portal vein main trunk diameter(PVMD),portal vein velocity(PVV),shear wave velocity(SWV),liver stiffness measurement(LSM),serum liver fibrosis markers(hyaluronic acid[HA],laminin[LN],procollagen typeⅢN-terminal peptide[PⅢNP],collagen type Ⅳ[CⅣ],aspartate aminotransferase to platelet ratio index[APRI],fibrosis-4 index[FIB-4]),and iron metabolism indicators(serum iron[SI],ferritin[FT])were compared before and after treatment.The relationship between baseline iron metabolism markers and ultrasonographic parameters,as well as serum liver fibrosis markers,was analyzed.Clinical efficacy,traditional Chinese medicine(TCM)syndrome scores,and adverse reactions were also compared between the groups.Additionally,bioinformatics analysis was performed to identify potential targets of Gandou Fumu Decoction for WD treatment.Peripheral blood mononuclear cells were collected from a normal group of 20 healthy individuals,as well as from both the control and observation groups before and after treatment.Real time fluorogenic quantitative PCR was performed to validate the expression changes of these targets across the groups.Results Compared with pre-treatment values,no significant changes were observed in PVMD levels in either group after treatment.No significant change in PVV was observed in the control group,whereas a significant decrease was noted in the observation group(P＜0.01).SWV,LSM,HA,LN,PⅢNP,CⅣ,APRI,FIB-4,and FT levels were significantly reduced compared to pre-treatment levels(P＜0.05,P＜0.01),whereas SI remained unchanged.Compared with the control group,the observation group had no significant difference in PVMD but had significantly lower PVV,SWV,LSM,HA,LN,PⅢNP,CⅣ,APRI,FIB-4,and FT levels(P＜0.05,P＜0.01),whereas SI remained unchanged.The total effective rate of treatment in the observation group was significantly higher than that in the control group(P＜0.05).Both groups showed a significant reduction in TCM syndrome scores after treatment(P＜0.01),with a significantly greater reduction observed in the observation group(P＜0.01).No significant adverse reactions were reported during treatment.Before treatment,there was no significant correlation between the SI of both groups and PVMD,PVV,SWV,LSM,HA,LN,PⅢNP,CⅣ,APRI,and FIB-4.In the observation group,FT showed a positive correlation with SWV,LSM,LN,PⅢNP,CⅣ,APRI,and FIB-4(P＜0.05,P＜0.01),while in the control group,FT showed a positive correlation with HA,LN,PⅢNP,CⅣ,APRI,and FIB-4(P＜0.01).After treatment,in the control group,SI showed a positive correlation with APRI and FIB-4(P＜0.05,P＜0.01),but there was no significant correlation between SI in the observation group and FT in both groups with the above-mentioned indicators.Bioinformatics analysis identified four potential targets of Gandou Fumu Decoction for treating WD,namely heme oxygenase 1(HMOX1),peroxisome proliferator-activated receptor alpha(PPARα),small heat shock protein B1(HSPB1),and mitogen-activated protein kinase 3(MAPK3).Compared to the normal group,both the control and observation groups had significantly lower PPARαand HSPB1 expression and significantly higher HMOX1 and MAPK3 expression before treatment(P＜0.01).Compared to before treatment within the same group,both groups showed significantly increased PPARα and HSPB1 expression and significantly decreased HMOX1 and MAPK3 expression after treatment(P＜0.05,P＜0.01).After treatment,the observation group had significantly higher PPARα and HSPB1 expression and lower HMOX1 and MAPK3 expression than the control group(P＜0.05,P＜0.01).Conclusion Gandou Fumu Decoction demonstrates remarkable advantages in improving clinical efficacy,Chinese medicine syndrome scores,iron metabolism,liver fibrosis progression,ultrasound imaging parameters,and ferroptosis-related biomarkers expression in patients with WD,with a favorable safety profile.

AIM:This study aims to design pH/near-infrared(NIR)dual-responsive metal-organic framework composite nanoparticles co-loaded with indocyanine green(ICG)and sphingosine kinase 1(SphK1)siRNA(siSphK1),and to evaluate their anticancer efficacy against non-small-cell lung cancer A549 cells.METHODS:The ZIF-8 nanopar-ticles were synthesized and loaded with ICG and siSphK1 to prepare ZIF-8@ICG@siSphK1 nanoparticles.Their morpholo-gy,particle size,surface charge,and crystalline structure were characterized through transmission electron microscopy,dynamic light scattering,and X-ray diffraction.Stability,siSphK1 encapsulation and protection,and pH/NIR response were assessed.The gene silencing efficacy and anticancer activity in A549 cells were evaluated using Western blot,RT-qPCR,MTT assay,flow cytometry,and reactive oxygen species(ROS)fluorescence staining.RESULTS:The ZIF-8@ICG@siSphK1 nanoparticles exhibited a typical polyhedral structure with an average particle size of(76.8±0.9)nm and a ζ potential of(9.2±0.1)mV.The nanoparticles effectively encapsulated siSphK1,protecting it from RNase degra-dation,and demonstrated excellent NIR responsiveness with a photothermal conversion efficiency of 39.7%.After 10 h of 808 nm laser irradiation,siRNA cumulative release was significantly higher at pH 5.5 compared with pH 7.4.In A549 cells,the nanoparticles efficiently delivered siSphK1 under NIR irradiation,significantly down-regulated SphK1 gene ex-pression,inhibited cell proliferation,induced apoptosis,and increased intracellular ROS levels.CONCLUSION:The ZIF-8@ICG@siSphK1 nanoparticles effectively induce cytotoxic effects against A549 cells through gene silencing and pho-tothermal therapy.

Objective:To explore the effects of childhood trauma on resting blood pressure, heart rate, and heart rate variability in patients with depression.Methods:A cross-sectional study was designed to prospectively collect clinical data on a total of 163 patients with depression, including 47 males and 116 females, aged 18-50 years,with mean[ M( Q1, Q3)] [29.0, (21.0, 37.0)]years, who were either the outpatients or the inpatients in the Mental Health Center of the First Hospital of Hebei Medical University from September 2022 to June 2024. The Childhood Trauma Questionnaire-Short form (CTQ-SF) was used to assess the experience of abuse and neglect during childhood. According to the CTQ-SF score, the subjects were divided into a trauma group ( n=80) and a non-trauma group ( n=83). The 17-item Hamilton Depression Scale (HAMD 17) and Hamilton Anxiety Scale (HAMA) were used to assess depressive and anxiety symptoms in the participants, respectively. A digital blood pressure monitor and an autonomic nervous system response detector were employed to measure resting blood pressure, heart rate, and heart rate variability (HRV). Spearman correlation analysis was used to examine the relationships between childhood trauma and resting blood pressure, heart rate, and HRV. Multiple linear regression analysis was performed to analyze factors influencing these parameters. The Bootstrap method was employed to test the potential mediating role of parasympathetic nervous system activity in the relationships between childhood trauma and resting blood pressure, and heart rate. Results:No significant difference was observed in resting heart rate between the trauma and non-trauma groups ( P>0.05). However, the trauma group exhibited higher resting systolic and diastolic blood pressure [(123.3±9.1) mmHg (1 mmHg=0.133 kPa) vs(116.9±10.8) mmHg, (80.0±8.6) mmHg vs (77.0±8.0) mmHg; Z=4.08, 2.24, all P<0.05]. HRV indices, including the standard deviation of normal to normal interval (SDNN), root mean square of successive differences (RMSSD), total power (TP), low frequency (LF), and high frequency (HF), were significantly lower in the trauma group [25.3 (19.4, 30.4) me vs 36.3 (27.4, 49.0) ms, 18.3 (12.9, 27.2) me vs 26.2 (19.0, 38.5) ms, 6.0(5.4, 6.5)ms 2vs 7.0(6.3, 7.4)ms 2,4.4(3.7,5.3)ms 2vs 5.8(4.9,6.3)ms 2, 4.2(3.4, 5.2)ms 2vs 5.2(4.6, 6.1)ms 2, respectively; all P<0.001]. Spearman correlation analysis showed that childhood trauma experiences in patients with depression were positively correlated with resting systolic blood pressure and diastolic blood pressure ( r=0.309, 0.236; P<0.01), childhood trauma was negatively correlated with HRV (SDNN, RMSSD, TP, LF, HF) ( r=-0.264, -0.274, -0.271, -0.235, -0.279; all P<0.01). Multiple linear regression analysis showed that childhood trauma was positively correlated with resting-state systolic blood pressure and resting-state diastolic blood pressure ( β=0.305, 0.291; all P<0.001). Childhood trauma was negatively correlated with RMSSD, TP, LF, and HF( β=-0.244, -0.249, -0.233, -0.263; all P<0.01). Mediation effect analysis showed that parasympathetic activity partially mediated the relationship between childhood trauma and resting systolic blood pressure (effect size 0.04, standard error 0.02, 95% CI=0.01-0.09), accounting for 14.29% (0.04/0.28) of the total effect. Conclusion:Childhood trauma experiences are associated with elevated resting blood pressure and reduced HRV in patients with depression. Decreased parasympathetic activity partially mediates the relationship between childhood trauma and elevated resting systolic blood pressure in these patients.

Objective:To explore the effects of the deep Theta burst stimulation (dTBS) applied to the bilateral dorsolateral prefrontal cortex on depressive symptoms and executive functions in patients with depression.Methods:The clinical data of a total of 98 patients with depression who were outpatients and inpatients in the Mental Health Center of the First Hospital of Hebei Medical University from June 2023 to October 2024 were prospectively collected, including 37 males and 61 females, aged 18-65 (37.4±13.3) years. Patients were randomly assigned to one of three groups: an active dTBS+drug therapy group (active stimulation group, n=33), a sham dTBS+drug therapy group (sham stimulation group, n=32), and a drug therapy group ( n=33). A shielding cover was added over the sham dTBS coil to increase the distance between the coil and the cortical surface, thereby achieving the sham stimulation effect. During each treatment, both active and sham dTBS were first applied by 1, 200 pulses of intermittent dTBS (diTBS) to the left dorsolateral prefrontal cortex, followed by 600 pulses of continuous dTBS (dcTBS) to the right dorsolateral prefrontal cortex. Before treatment and two weeks after treatment, the Hamilton Anxiety Scale (HAMA) and 17-Item Hamilton Depression Scale (HAMD 17) were used to evaluate patients′ depression and anxiety, and the Symbol Digit Coding Test of the Chinese Brief Cognitive Test (C-BCT) was used to assess the executive functions. The 32-item Hypomania Checklist (HCL-32) as well as the Mood Disorder Questionnaire (MDQ) were used to evaluate the risk of treatment-emergent mania. The primary outcomes included reduction rate in HAMD 17 and HAMA scores, as well as changes in the Symbol Digit Coding Test of the C-BCT. Secondary outcomes encompassed HAMD 17 treatment response rate, adverse events, and the risk of treatment-emergent mania. The differences in efficacy between the three groups were compared using one-way ANOVA and LSD post-hoc analysis (reduction rate in HAMD 17 scores, reduction rate in HAMA scores, and changes in the Symbol Digit Coding Test of the C-BCT). Results:At the end of the 2nd week of the treatment, the HAMD 17 reduction rate in the active stimulation group was higher than the sham stimulation group and the drug therapy group, with a significant difference (59.4 (46.9, 80.2) % vs 47.6 (31.2, 58.3) %, H=18.95, P=0.006; 59.4 (46.9, 80.2) % vs 35.5 (20.0, 50.0) %, H=31.10, P<0.001). The HAMA reduction rate in the active stimulation group and the sham stimulation group were higher than the drug therapy group, with a significant difference (52.6 (43.5, 65.7) % vs 2.1 (21.1, 58.8) %, H=21.31, P=0.002; 52.9 (41.7, 62.5) % vs 32.1 (21.1, 58.8) %, H=14.4, P=0.037). The changes in the symbol digit coding test of the C-BCT in the active stimulation group were significantly higher than the sham stimulation group and the drug therapy group (6.3±2.1 scores vs 2.9±3.2 scores, F=5.02, P=0.011; 6.3±2.1 scores vs 2.8±3.1 scores, F=5.02, P=0.009). The incidence rate of adverse events in the active stimulation group was 12.1% (4/33) and 3.1% (1/32) in the sham stimulation group, and there was no significant difference in the incidence of adverse events between the two groups (χ 2=0.17, P=0.355). Conclusion:Bilateral dTBS stimulation of the dorsolateral prefrontal cortex combined with drug therapy can improve depressive symptoms and executive functions, such as information processing speed, attention and working memory.