Objective: To explore the relationship between socio ecological risk factors (SERF), physical activity (PA) developmental trajectories, and depressive symptoms among junior and senior high school students in Tianjin, in order to provide theoretical support for comprehensive interventions for adolescent depression. Methods: A longitudinal follow up design was adopted. In September 2022, a baseline survey was conducted using a stratified cluster random sampling method in two junior high schools and two senior high schools in Tianjin, collecting data on students basic information, SERF, PA, and depressive symptoms. Two follow up surveys were conducted in September 2023 and 2024, yielding 588 valid participants. Latent class growth analysis (LCGA) was used to identify PA developmental trajectory categories among junior and senior high school students. Logistic regression was applied to examine the associations between depressive symptoms and SERF as well as PA trajectories. Results: The detection rates of depressive symptoms among Tianjin junior and senior high school students over the three years were 26.53%, 20.24%, and 21.26 %, respectively. Depressive symptoms were positively correlated with SERF ( OR=1.04, 95%CI=1.03-1.05, P <0.05). The highest risks were observed in the individual dimension and family dimension ( OR =1.28, 1.21, both P <0.05). LCGA identified three PA trajectory groups:persistently low level (80.65%), persistently high level (4.58%), and slowly increasing group ( 14.77 %). Multivariate regression analysis showed that compared with the persistently low level PA, the slowly increasing PA significantly reduced the risk of depressive symptoms ( OR=0.44, 95%CI =0.20-0.88), while SERF still increased the risk of depressive symptoms ( OR=1.04, 95%CI =1.03-1.05) (both P <0.05). Conclusion SERF are risk factors for depression symptoms among junior and senior high school students, whereas slowly increasing PA development trajectory demonstrates a protective effect.

ObjectiveTo investigate the distribution of traditional Chinese medicine （TCM） syndrome patterns among postmenopausal women with dyslipidemia， and to examine the correlations of lipid parameters with bone mineral density （BMD） and bone metabolism markers across common TCM syndrome patterns， thereby providing a clinical reference for individualized integrative traditional Chinese and western medicine interventions stratified according to TCM syndrome patterns. MethodsA multi-center cross-sectional study was conducted among postmenopausal women aged 45-64 years with dyslipidemia. TCM syndromes were determined using a scale-based scoring method. BMD measurements were collected， and fasting venous blood samples were assayed for lipid parameters including total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C）， and bone metabolism biomarkers including osteocalcin （OST）， total procollagen type Ⅰ N-terminal propeptide （P1NP）， alkaline phosphatase （ALP）， bone-specific alkaline phosphatase （BALP）， β-isomerized C-terminal telopeptide of type Ⅰ collagen （β-CTX）， 25-hydroxyvitamin D ［25（OH）D］， and thyroid-stimulating hormone （TSH）. Chi-square tests were used to compare the distribution of dyslipidemia across different TCM syndromes. Spearman's rank correlation analysis was performed to evaluate the correlations between TCM syndrome patterns and dyslipidemia， as well as the correlations of lipid parameters with BMD and bone metabolism markers within each syndrome pattern. ResultsA total of 506 postmenopausal women with dyslipidemia were included， comprising 172 cases of spleen-kidney yang deficiency syndrome （33.99%）， 163 cases of phlegm-turbidity obstruction syndrome （32.21%）， 118 cases of liver-kidney yin deficiency syndrome （23.32%）， 33 cases of qi stagnation and blood stasis syndrome （6.52%）， and 20 cases of yin deficiency and yang hyperactivity syndrome （3.95%）. Phlegm-turbidity obstruction syndrome was negatively correlated with TC abnormality （r=-0.120， P=0.007） and positively correlated with TG abnormality （r=0.246， P＜0.001）. Spleen-kidney yang deficiency syndrome and liver-kidney yin deficiency syndrome were both negatively correlated with TG abnormality （r=-0.101， P=0.023； r=-0.116， P=0.009， respectively）. Further correlation analysis confirmed that phlegm-turbidity obstruction syndrome was negatively correlated with TC abnormality （r=-0.120） and significantly positively correlated with TG abnormality （r=0.246）. Both the spleen-kidney yang deficiency syndrome and liver-kidney yin deficiency syndrome were negatively correlated with TG abnormality （r=-0.101 and r=-0.116， respectively）. In patients with phlegm-turbidity obstruction syndrome， HDL-C was negatively correlated with BMD at the left femoral neck （r=-0.178， P=0.023） and at left total hip （r=-0.190， P=0.015）. In patients with liver-kidney yin deficiency syndrome， TG was positively correlated with BMD at the lumbar spine （L1-L4） and left total hip （r=0.214， P=0.020； r=0.221， P=0.016， respectively）. More significant correlations were observed in patients with spleen-kidney yang deficiency syndrome， TG was positively correlated with ALP （r=0.210， P=0.006）； TC was positively correlated with TSH and 25（OH）D （r=0.153， P=0.045； r= 0.231， P=0.002， respectively）； HDL-C was positively correlated with OST and 25（OH）D （r=0.156， P=0.040； r=0.228， P=0.003， respectively）； and LDL-C was positively correlated with TSH and 25（OH）D （r=0.156， P= 0.041； r=0.182， P=0.017， respectively）. In patients with liver-kidney yin deficiency syndrome， HDL-C was negatively correlated with TSH （r=-0.204， P=0.027）. ConclusionThe association between dyslipidemia and skeletal health in postmenopausal women varies across TCM syndromes. Lipid abnormalities in women with phlegm-turbidity obstruction syndrome or liver-kidney yin deficiency syndrome are accompanied primarily by site-specific alterations in BMD， whereas those in women with spleen-kidney yang deficiency syndrome are reflected mainly in changes in bone metabolism markers. These findings suggest that targeted intervention strategies should be developed according to TCM syndrome characteristics for postmenopausal women with dyslipidemia.

ObjectiveTo investigate the distribution of traditional Chinese medicine （TCM） syndrome patterns among postmenopausal women with dyslipidemia， and to examine the correlations of lipid parameters with bone mineral density （BMD） and bone metabolism markers across common TCM syndrome patterns， thereby providing a clinical reference for individualized integrative traditional Chinese and western medicine interventions stratified according to TCM syndrome patterns. MethodsA multi-center cross-sectional study was conducted among postmenopausal women aged 45-64 years with dyslipidemia. TCM syndromes were determined using a scale-based scoring method. BMD measurements were collected， and fasting venous blood samples were assayed for lipid parameters including total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C）， and bone metabolism biomarkers including osteocalcin （OST）， total procollagen type Ⅰ N-terminal propeptide （P1NP）， alkaline phosphatase （ALP）， bone-specific alkaline phosphatase （BALP）， β-isomerized C-terminal telopeptide of type Ⅰ collagen （β-CTX）， 25-hydroxyvitamin D ［25（OH）D］， and thyroid-stimulating hormone （TSH）. Chi-square tests were used to compare the distribution of dyslipidemia across different TCM syndromes. Spearman's rank correlation analysis was performed to evaluate the correlations between TCM syndrome patterns and dyslipidemia， as well as the correlations of lipid parameters with BMD and bone metabolism markers within each syndrome pattern. ResultsA total of 506 postmenopausal women with dyslipidemia were included， comprising 172 cases of spleen-kidney yang deficiency syndrome （33.99%）， 163 cases of phlegm-turbidity obstruction syndrome （32.21%）， 118 cases of liver-kidney yin deficiency syndrome （23.32%）， 33 cases of qi stagnation and blood stasis syndrome （6.52%）， and 20 cases of yin deficiency and yang hyperactivity syndrome （3.95%）. Phlegm-turbidity obstruction syndrome was negatively correlated with TC abnormality （r=-0.120， P=0.007） and positively correlated with TG abnormality （r=0.246， P＜0.001）. Spleen-kidney yang deficiency syndrome and liver-kidney yin deficiency syndrome were both negatively correlated with TG abnormality （r=-0.101， P=0.023； r=-0.116， P=0.009， respectively）. Further correlation analysis confirmed that phlegm-turbidity obstruction syndrome was negatively correlated with TC abnormality （r=-0.120） and significantly positively correlated with TG abnormality （r=0.246）. Both the spleen-kidney yang deficiency syndrome and liver-kidney yin deficiency syndrome were negatively correlated with TG abnormality （r=-0.101 and r=-0.116， respectively）. In patients with phlegm-turbidity obstruction syndrome， HDL-C was negatively correlated with BMD at the left femoral neck （r=-0.178， P=0.023） and at left total hip （r=-0.190， P=0.015）. In patients with liver-kidney yin deficiency syndrome， TG was positively correlated with BMD at the lumbar spine （L1-L4） and left total hip （r=0.214， P=0.020； r=0.221， P=0.016， respectively）. More significant correlations were observed in patients with spleen-kidney yang deficiency syndrome， TG was positively correlated with ALP （r=0.210， P=0.006）； TC was positively correlated with TSH and 25（OH）D （r=0.153， P=0.045； r= 0.231， P=0.002， respectively）； HDL-C was positively correlated with OST and 25（OH）D （r=0.156， P=0.040； r=0.228， P=0.003， respectively）； and LDL-C was positively correlated with TSH and 25（OH）D （r=0.156， P= 0.041； r=0.182， P=0.017， respectively）. In patients with liver-kidney yin deficiency syndrome， HDL-C was negatively correlated with TSH （r=-0.204， P=0.027）. ConclusionThe association between dyslipidemia and skeletal health in postmenopausal women varies across TCM syndromes. Lipid abnormalities in women with phlegm-turbidity obstruction syndrome or liver-kidney yin deficiency syndrome are accompanied primarily by site-specific alterations in BMD， whereas those in women with spleen-kidney yang deficiency syndrome are reflected mainly in changes in bone metabolism markers. These findings suggest that targeted intervention strategies should be developed according to TCM syndrome characteristics for postmenopausal women with dyslipidemia.

Objective: Accurate evaluation of inflammation severity in ulcerative colitis (UC) can guide treatment strategy selection. The potential value of the pericolic fat attenuation index (FAI) on CT as an indicator of disease severity remains unknown.This study aimed to assess the diagnostic accuracy of pericolic FAI in predicting UC severity. Materials and Methods: This retrospective study enrolled 148 patients (mean age 48 years; 87 males). The fat attenuation on CT was measured in four different locations: the mesocolic vascular side (MS) and opposite side of MS (OMS) around the most severe bowel lesion, the retroperitoneal space (RS), and the subcutaneous area. The fat attenuation indices (FAI MS, FAI OMS, and FAI RS) were calculated as the fat attenuation measured in MS, OMS, and RS, respectively, minus that of the subcutaneous area, and were obtained in the non-enhanced, arterial, and delayed phases. Correlations between the FAI and UC Endoscopic Index of Severity (UCEIS) were assessed using Spearman’s correlation. Predictors of severe UC (UCEIS ≥7) were selected by univariable analysis. The performance of FAI in predicting severe UC was evaluated using the area under the receiver operating characteristic curve (AUC). Results: The FAIMS and FAI OMS scores were significantly higher than FAI RS in three phases (all P < 0.001). The FAIMS and FAI OMS scores moderately correlated with the UCEIS score (r = 0.474–0.649 among the three phases). Additionally, FAI MS and FAI OMS identified severe UC, with AUC varying from 0.77 to 0.85. Conclusion Increased CT attenuation of pericolic adipose tissue could serve as a noninvasive marker for evaluating UC severity. FAI MS and FAI OMS of three phases showed similar prediction accuracies for severe UC identification.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

OBJECTIVE: To investigate the feasibility and prognostic implications of assessing volume status during early fluid resuscitation in septic patients based on estimated plasma volume status (ePVS). METHODS: A prospective study was conducted. Patients with sepsis admitted to intensive care unit (ICU) of the First Affiliated Hospital of Kunming Medical University from March to December in 2023 were enrolled. The general information and laboratory indicators at ICU admission were recorded, and ePVS, sequential organ failure assessment (SOFA) score, acute physiology and chronic health status evaluation II (APACHE II) score were calculated. The vital signs, arterial blood gas analysis and volume status related indicators before liquid resuscitation (T0h) and 3 hours (T3h) and 6 hours (T6h) of fluid resuscitation were recorded. The diameter and variability of the inferior vena cava (IVC) were measured by ultrasound, and ePVS, percentage change value of estimated plasma volume status (ΔePVS%), difference in central venous-to-arterial partial pressure of carbon dioxide (Pcv-aCO₂), and lactate clearance rate (LCR) were calculated. Patients were divided into sepsis group and septic shock group based on the diagnosis at ICU admission, and septic patients were subdivided into survival group and death group based on their 28-day survival status. The differences in clinical data between the groups were compared. The correlation between ePVS or ΔePVS% and volume status related indicators during early liquid resuscitation was analyzed by Spearman rank sum correlation test. The predictive value of each variable for 28-day survival in patients with sepsis was analyzed by receiver operator characteristic curve (ROC curve), and 28-day death risk factors were analyzed by Logistic regression method. RESULTS: Fifty-four septic patients were enrolled in the final analysis, including 17 with sepsis and 37 with septic shock; 34 survived at 28 days and 20 died, with a 28-day survival rate of 63.0%. Compared with the sepsis group, the septic shock group had a lower venous ePVS at ICU admission [dL/g: 4.96 (3.67, 7.15) vs. 7.55 (4.36, 10.07), P < 0.05]. Compared with the death group, the survival group had higher T6h arterial and venous ΔePVS%, and albumin [Alb; T6h arterial ΔePVS% (%): 11.57% (-1.82%, 31.35%) vs. 0.48% (-5.67%, 6.02%), T6h venous ΔePVS%: 9.62% (3.59%, 25.75%) vs. 1.52% (-9.65%, 7.72%), Alb (g/L): 27.57±4.15 vs. 23.77±6.97, all P < 0.05], lower SOFA score, APACHE II score, AST, T0h Lac, and T3h and T6h norepinephrine dosage [SOFA score: 9.00 (8.00, 10.00) vs. 11.50 (9.25, 14.50), APACHE II score: 18.00 (14.75, 21.25) vs. 25.50 (21.00, 30.00), AST (U/L): 34.09 (23.20, 56.64) vs. 79.24 (25.34, 196.59), T0h Lac (mmol/L): 1.75 (1.40, 2.93) vs. 3.25 (2.33, 5.30), norepinephrine dosage (mg): 0.98 (< 0.01, 3.10) vs. 4.60 (1.05, 8.55) at T3h, 1.82 (0.38, 5.30) vs. 8.20 (2.80, 17.73) at T6h, all P < 0.05]. While there were no significantly differences in other basic data and ePVS at all of the time points before and after resuscitation between the two groups. Correlation analysis showed that T6h venous ePVS was significantly positively correlated with T6h IVC variability in septic patients (r = 0.360, P < 0.05), T0h arterial ePVS was significantly negatively correlated with T3h and T6h liquid intake volume (r₁ = -0.367, r₂ = -0.280, both P < 0.05), and venous ePVS at ICU admission was significantly positively correlated with NT-proBNP at ICU admission (r = 0.409, P < 0.05). T6h venous ΔePVS% was significantly positively correlated with T3h liquid intake volume and T6h LCR (r₁ = 0.286, r₂ = 0.286, both P < 0.05), and significantly negatively correlated with T6h urine volume and T6h change value of Pcv-aCO₂ (ΔPcv-aCO₂; r₁ = -0.321, r₂ = -0.371, both P < 0.05). ROC curve analysis showed that the area under the ROC curve (AUC) of T6h venous ΔePVS% for predicting 28-day survival in septic patients was 0.726 [95% confidence interval (95%CI) was 0.578-0.875, P = 0.006], with a sensitivity of 82.4%, a specificity of 60.0%, and an optimal cut-off value of 3.09%. Binary multifactorial Logistic regression analysis showed that an increase in T6h venous ΔePVS% was a protective factor for 28-day death in patients with sepsis on early fluid resuscitation [odds ratio (OR) = 0.900, 95%CI was 0.834-0.972, P = 0.007]. CONCLUSIONS ePVS may have potential for assessing the volume status of septic patients during early fluid resuscitation. The ΔePVS% during early fluid resuscitation may help to identify septic patients with a poor prognosis.
Humans ; Prognosis ; Fluid Therapy ; Sepsis/physiopathology* ; Prospective Studies ; Plasma Volume ; Intensive Care Units ; Resuscitation ; Male ; Female ; Middle Aged ; Shock, Septic/therapy*

Objective: Accurate evaluation of inflammation severity in ulcerative colitis (UC) can guide treatment strategy selection. The potential value of the pericolic fat attenuation index (FAI) on CT as an indicator of disease severity remains unknown.This study aimed to assess the diagnostic accuracy of pericolic FAI in predicting UC severity. Materials and Methods: This retrospective study enrolled 148 patients (mean age 48 years; 87 males). The fat attenuation on CT was measured in four different locations: the mesocolic vascular side (MS) and opposite side of MS (OMS) around the most severe bowel lesion, the retroperitoneal space (RS), and the subcutaneous area. The fat attenuation indices (FAI MS, FAI OMS, and FAI RS) were calculated as the fat attenuation measured in MS, OMS, and RS, respectively, minus that of the subcutaneous area, and were obtained in the non-enhanced, arterial, and delayed phases. Correlations between the FAI and UC Endoscopic Index of Severity (UCEIS) were assessed using Spearman’s correlation. Predictors of severe UC (UCEIS ≥7) were selected by univariable analysis. The performance of FAI in predicting severe UC was evaluated using the area under the receiver operating characteristic curve (AUC). Results: The FAIMS and FAI OMS scores were significantly higher than FAI RS in three phases (all P < 0.001). The FAIMS and FAI OMS scores moderately correlated with the UCEIS score (r = 0.474–0.649 among the three phases). Additionally, FAI MS and FAI OMS identified severe UC, with AUC varying from 0.77 to 0.85. Conclusion Increased CT attenuation of pericolic adipose tissue could serve as a noninvasive marker for evaluating UC severity. FAI MS and FAI OMS of three phases showed similar prediction accuracies for severe UC identification.