OBJECTIVE To observe the effects of endogenous metabolite mesaconate combined with Sodium lactate Ringer’s injection （LR） on prolonging the golden treatment time window and its resuscitation efficacy in rats with hemorrhagic shock under high-altitude conditions. METHODS Rats were divided into the shock group， LR group， and 5， 20， 50 mg/kg mesaconate+LR groups， with 20 rats in each group， to investigate the effect of additional use of mesaconate on the golden treatment time window. After establishing a model of uncontrolled hemorrhagic shock under high-altitude conditions in all groups by housing in a hypobaric hypoxia chamber combined with splenic artery transection， rats in the shock group received no resuscitation， while rats in the LR group and mesaconate+LR groups underwent low-pressure resuscitation with LR or mesaconate combined with LR. Blood pressure control， fluid infusion volume， blood loss rate and survival status were observed in each group. Rats were further divided into the normal group， shock group and mesaconate （50 mg/kg）+LR group， with 10 or 20 rats in each group， to evaluate the resuscitation effects after extending the golden treatment time window by additionally using mesaconate. Except for the normal group， the other groups underwent the same procedure to establish an uncontrolled hemorrhagic shock model under high-altitude conditions. Rats in the shock group received no resuscitation. In the mesaconate+LR group， after 3 h of low-pressure resuscitation， bleeding control was performed by ligation of the spleen artery， and the infusion volume and blood loss rate were recorded； subsequently， the rats received LR resuscitation with twice the volume of blood loss. Then， blood gas indicators of the mesaconate+LR group were measured at different time points. Survival rates， indicators related to sublingual microcirculatory perfusion， liver and kidney blood flow， indicators related to the function of vital organs， and lung and brain water content were observed in all groups. RESULTS LR infusion alone could effectively maintain mean arterial pressure （MAP） within 50-60 mmHg for approximately 1 h. The administration of mesaconate combined with LR during hypotensive resuscitation could maintain MAP within 50-60 mmHg for over 3 h， with significantly reduced fluid infusion volume and blood loss rate in 50 mg/kg mesaconate+LR group， compared to the LR group （ P ＜0.05）. In the LR group， rats maintained low pressure for up to 1 hour with a survival rate of 52.94%， and no rats survived beyond 2 h. In the 5， 20 and 50 mg/kg mesaconate+LR groups， rats maintained low pressure for up to 1 h with a survival rate exceeding 80%； in the 20 and 50 mg/kg mesaconate+LR groups， rats maintained low pressure for up to 3 h with a survival rate exceeding 70%. After complete resuscitation with mesaconate combined with LR， the 72 h survival rate of rats was 43.75%， and significant improvements in blood gas parameters were observed compared to the end of the shock phase （ P ＜0.05）. Compared to the shock group， the mesaconate+LR group showed significant recovery in sublingual microcirculatory indicators， and liver/kidney blood flow after complete resuscitation （ P ＜0.05）， with significant reductions in heart， liver and kidney function-related indicators and lung water content （ P ＜0.05）. CONCLUSIONS Mesaconate combined with LR significantly extends the golden treatment time window for hemorrhagic shock in rats under high-altitude conditions， improves blood gas parameters， sublingual microcirculatory perfusion， and liver/kidney blood flow， mitigates vital organ impairment and pulmonary edema， and increases the survival rate of shocked rats.

Objective: To explore the developmental trajectories of depression in children and adolescents and their association with family types, and to analyze the role of being an only child in the context, so as to provide a basis for early identification of mental health issues in children and adolescents. Methods: The study was a secondary analysis based on the existing database of the Jiangsu Provincial Student Common Diseases and Health Influencing Factors Monitoring and Intervention Project. A total of 11 502 students who had completed at least two measurements using the Chinese version of the Center for Epidemiologic Studies Depression Scale (CES-D) between 2022 and 2024, and had complete information on family type, gender, and age, were selected as the study subjects. Latent class trajectory modeling was used to identify depression developmental trajectories. Multinomial Logistic regression was applied to analyze the association between family type and depression developmental trajectories, and the interaction effect of family type and being an only child was tested. Results: Three types of depression developmental trajectories were identified among children and adolescents: low stable type (91.3%, 10 504 students), moderate rising type (4.3%, 500 students), and high declining type (4.3%, 498 students). Significant differences were observed among the different trajectory groups in terms of gender, age, parental education level, family type, baseline CES-D score, and baseline school type ( χ 2/H=17.48, 139.97, 19.72 , 30.77, 1 081.35, 220.81, all P <0.05). Multinomial Logistic regression analysis showed that, using the low stable type as the reference trajectory group and the nuclear family as the reference family type, after adjusting for confounding factors such as gender, age, and parental education level, single parent families ( OR=1.87, 95%CI= 1.16-3.03) and grandparent headed families ( OR=1.83, 95%CI =1.04-3.21) were significantly associated with the high declining type trajectory (both P <0.05). No significant association was found between family type and the moderate rising type trajectory (all P >0.05). The interaction effect between family type and being an only child was not statistically significant ( LRT=7.71, df=8, P =0.46). Conclusions Depressive symptoms in children and adolescents show heterogeneous developmental patterns during school age. Children and adolescents from single parent and intergenerational families are more likely to follow the high decreasing trajectory.

Objective:To compare the efficacy of hepatic artery infusion chemotherapy (HAIC) combined with targeted therapy and immunnotherapy and transarterial chemoembolization (TACE) combined with targeted therapy and immunnotherapy in the treatment of unresectable hepatocellular carcinoma HCC.Methods:We retrospectively analyzed the clinical data of 40 patients with unresectable HCC treated with HAIC combined with targeted therapy and immunnotherapy and TACE combined with targeted therapy and immunnotherapy in Tongde Hospital of Zhejiang Province and Zhejiang Provincial People's Hospital.The patients were divided into HAIC group ( n=14) and TACE group ( n=26) according to the different treatment methods. Baseline data, surgical conversion and intraoperative situation, tumor response, portal vein cancer thrombus control rate, leukocyte reduction rate, platelet reduction rate, incidence of liver function abnormalities, objective remission rate, and disease control rate were compared between the two groups. Results:The HAIC group had a later baseline tumor staging than the TACE group (higher percentage of portal vein cancer thrombus, CNLC stage Ⅲa).The surgical conversion rate of the HAIC and TACE groups were 28.6%(4/14) and 26.9%(7/26), respectively, with the difference of no statistical significance ( P>0.05);The operation time and intraoperative bleeding were (329.5±19.9) min vs.(413.4±26.4) min, (272.2±49.9) ml vs.(536.0±123.6) ml, and the differences were statistically significant ( P<0. 05); The maximum tumor diameter reduction rate [(30.7%±15.1%) vs.(7.2%±12.6%)] and portal vein cancer thrombus control rate [100% (12/12) vs. 64.3% (9/14)], the differences were statistically significant ( P<0.05);The incidences of leukocyte and platelet decrease in the two groups during the course of treatment were 71.4%(10/14) vs. 34.6%(9/26)、78.5%(11/14) vs. 38.5%(10/26), and the incidences of liver function abnormalities were 35.7%(5/14) vs. 69.2%(18/26), the differences were statistically significant ( P<0.05);The objective response rate and disease control rate were 57.1%(8/14) vs. 30.8% (8/26)、71.4% (10/14) vs. 53.8%(14/26), all statistically significant. Conclusion:HAIC combined with targeted therapy and immunnotherapy is a safe and effective treatment for middle and advanced HCC, especially suitable for patients with portal vein tumor thrombus(PVTT), large tumor, or poor liver function.

Objective:To construct a clinical decision-making ability indicator system based on evidence-based practice for pediatric nursing interns, and to provide a scientific basis for clinical teaching and evaluation.Methods:A method combining literature analysis, Delphi expert consultation, and empirical research was used. Firstly, a systematic search of Chinese and English databases (2018-2023) was conducted. Literature was screened based on the PICO framework and evidence-based data were extracted, resulting in a preliminary system consisting of 4 primary indicators, 12 secondary indicators, and 39 tertiary indicators. Subsequently, the indicators were revised through two rounds of Delphi expert consultation (25 experts with 19-27 years of work experience). The expert authority coefficients (Cr) were 0.898-0.907 and the Kendall's concordance coefficients were 0.351-0.420 ( P<0.001). Finally, the analytic hierarchy process was used to determine the weights, and the reliability and validity were verified through a questionnaire survey (sample size: 30 participants in preliminary survey and 58 participants in formal survey). Results:The constructed indicator system included 4 primary indicators (weights), 13 secondary indicators, and 42 tertiary indicators. The weights of the primary indicators were as follows: knowledge integration ability (0.300), evidence-based practice ability (0.250), clinical judgment ability (0.280), and ethical decision-making ability (0.170). The importance scores of all items exceeded 4.0 points (out of 5 points), and the coefficients of variation were less than 0.20. The reliability and validity tests showed that the Cronbach's α of the overall scale was 0.89, and the intraclass correlation coefficient was 0.88. The cumulative variance contribution rate of exploratory factor analysis was 69.30%. The confirmatory factor analysis demonstrated a good model fit with a comparative fit index of 0.93 and a root mean square error of approximation of 0.05. Conclusions:This indicator system has high scientificity and practicality, and can provide a reference for the standardized cultivation and evaluation of clinical decision-making ability of pediatric nursing interns. In the future, it is necessary to strengthen advanced evidence-based skills training and long-term application effectiveness tracking.

With the deepening of molecular biology and cell biology research,the regulatory mechanism of autophagy has been gradually revealed,providing new ideas for the treatment of numerous diseases.Autophagy may be closely related to pathological changes such as apoptosis resistance of fibroblast-like synoviocytes,disturbances in bone metabolic homeostasis,and antigen presentation,the regulation of autophagy homeostasis may be an important approach for the treatment of rheumatoid arthritis(RA).In this paper,we provide a review on the pathological mechanism of autophagy in RA,with a view to providing a theoretical basis for later studies.

Objective To compare the clinical outcomes of modified posterolateral approach and traditional posterolateral approach combined with open reduction and internal fixation via medial approach in treatment of trimalleolar fracture.Methods Sixty-two patients with trimalleolar fractures who underwent modified posterolateral approach combined with open reduction and internal fixation via medial approach from January 2019 to June 2022 in orthopedics department of our hospital were enrolled in the modified approach group,and 62 patients who underwent traditional posterolateral approach combined with open reduction and internal fixation via medial approach at the same period were matched as the traditional approach group.The perioperative indicators were collected.The range of ankle motion 12 months after surgery was measured.The Maryland score,American Orthopaedic Foot and Ankle Society(AOFAS)score and Baird-Jackson score were employed to evaluate the recovery of patients 12 months after surgery,and the occurence of complications was recorded.Results There was no significant difference in the operation time,intraoperative blood loss,incision length,postoperative drainage volume or pain score between the two groups(P<0.05).The Maryland scores,AOFAS scores and Baird-Jackson scores 12 months after surgery of the two groups were higher than those before operation(P<0.05),while there was no significant difference between the two groups(P<0.05).The range of ankle motion in the modified approach group was better than that in the traditional approach group,and the incidence of nerve injury after surgery was lower than that in the traditional approach group,with statistically significant differences(P<0.05).Conclusions The modified posterolateral approach combined with open reduction and internal fixation via medial approach in treatment of trimalleolar fracture can achieve good early clinical outcome,effectively improve range of ankle motion,and reduce postoperative nerve injury.

Objective To investigate the seroprevalence of antibody against Toxoplasma gondii among patients with hematological malignancies, and compare it with that among health individuals, so as to provide insights into unraveling the pathogenesis of hematological malignancies. Methods A total of 225 patients with hematological malignancies in Department of Hematology, Xuzhou Central Hospital and 300 healthy individuals in the same hospital were enrolled from 2017 to 2024. Blood samples were collected from all subjects, and the serum IgG and IgM antibodies against T. gondii were detected using chemiluminescent immunoassay. Demographic and clinical features were collected from patients with hematological malignancies, including gender, age, contact with cats, consumption of raw or undercooked meat, type of malignancy, clinical symptoms, blood transfusion and treatment, and the seroprevalence of anti-T. gondii antibody was compared among patients with different characteristics. Results The age (t = 0.72, P > 0.05) and gender (χ² = 0.93, P > 0.05) were compared between patients with hematological malignancies and healthy individuals. The seroprevalence of T. gondii infection was 20.89% among patients with hematological malignancies and 4.33% among healthy individuals (χ² = 34.81, P < 0.01), and the seroprevalence of anti-T. gondii IgG antibody was 20.89% among patients with hematological malignancies and 4.33% among healthy individuals (χ² = 34.81, P < 0.01), while there was no significant difference in the seroprevalence of anti-T. gondii IgM antibody between patients with hematological malignancies and healthy individuals (1.33% vs. 0; corrected χ² = 2.02, P > 0.05). The seroprevalence of T. gondii infection was 23.08% among patients with leukemia, 16.67% among patients with lymphoma, 19.23% among patients with multiple myeloma, 24.00% among patients with myeloproliferative neoplasm, and 26.09% among patients with myelodysplastic syndrome (χ² = 1.44, P > 0.05), and was all higher than among healthy individuals (corrected χ² = 23.92, 10.74, 13.76, 12.84 and 14.54; all P values < 0.01). In addition, there were no significant differences in the detection of anti-T. gondii antibody among patients with hematological malignancies in terms of gender, age, contact with cats, consumption of raw or undercooked meat, chemotherapy or blood transfusion (χ² = 0.76, 1.97, 0, 2.81, 2.38 and 0.66; all P values > 0.05). Conclusions There is a high risk of T. gondii infection among patients with hematological malignancies, and intensified surveillance of T. gondii infection is recommended among patients with hematological malignancies.

OBJECTIVE: Huachansu injection (HCSI), a promising anti-cancer Chinese medicine injection, has been reported to have the potential for reducing the toxicity of chemotherapy and improving the quality of life for colorectal cancer (CRC) patients. The objective of this study is to explore the synergistic and detoxifying effects of HCSI when used in combination with irinotecan (CPT-11). METHODS: To investigate the effect of HCSI on anti-CRC efficacy and intestinal toxicity of CPT-11, we measured changes in the biological behavior of LoVo cells in vitro, and anti-tumor effects in LoVo cell xenograft nude mice models in vivo. Meanwhile, the effect of HCSI on intestinal toxicity and the uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) expression was investigated in the CPT-11-induced colitis mouse model. Subsequently, we measured the effect of HCSI and its 13 constituent bufadienolides on the expression of UGT1A1 and organic anion transporting polypeptides 1B3 (OATP1B3) in HepG2 cells. RESULTS: The combination index (CI) results showed that the combination of HCSI and CPT-11 exhibited a synergistic effect (CI < 1), which significantly suppressing the LoVo cell migration, enhancing G2/M and S phase arrest, and inhibiting tumor growth in vivo. Additionally, the damage to intestinal tissues was attenuated by HCSI in CPT-11-induced colitis model, while the increased expression of UGT1A1 in HepG2 cells and in mouse was observed. CONCLUSION The co-therapy with HCSI alleviated the intestinal toxicity induced by CPT-11 and exerted an enhanced anti-CRC effect. The detoxifying mechanism may be related to the increased expression of UGT1A1 and OATP1B3 by HCSI and its bufadienolides components. The findings of this study may serve as a theoretical insights and strategies to improve CRC patient outcomes. Please cite this article as: Jiang B, Meng ZY, Hu YJ, Chen JJ, Zong L, Xu LY, Zhang XQ, Zhang JX, Han YL. Huachansu injection enhances anti-colorectal cancer efficacy of irinotecan and alleviates its induced intestinal toxicity through upregulating UGT1A1-OATP1B3 expression in vitro and in vivo. J Integr Med. 2025; 23(5):576-590.
Irinotecan/therapeutic use* ; Animals ; Glucuronosyltransferase/genetics* ; Humans ; Colorectal Neoplasms/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Mice, Nude ; Mice ; Up-Regulation/drug effects* ; Male ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Hep G2 Cells ; Cell Line, Tumor ; Intestines/drug effects* ; Amphibian Venoms

Triggering receptor expressed on myeloid cells 2 (TREM2)-mediated microglial phagocytosis is an energy-intensive process that plays a crucial role in amyloid beta (Aβ) clearance in Alzheimer's disease (AD). Energy metabolic reprogramming (EMR) in microglia induced by TREM2 presents therapeutic targets for cognitive impairment in AD. Jiawei Xionggui Decoction (JWXG) has demonstrated effectiveness in enhancing energy supply, protecting microglia, and mitigating cognitive impairment in APP/PS1 mice. However, the mechanism by which JWXG enhances Aβ phagocytosis through TREM2-mediated EMR in microglia remains unclear. This study investigates how JWXG facilitates microglial phagocytosis and alleviates cognitive deficits in AD through TREM2-mediated EMR. Microglial phagocytosis was evaluated through immunofluorescence staining in vitro and in vivo. The EMR level of microglia was assessed using high-performance liquid chromatography (HPLC) and enzyme-linked immunosorbent assay (ELISA) kits. The TREM2/protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway was analyzed using Western blotting in BV₂ cells. TREM2^-/- BV₂ cells were utilized for reverse validation experiments. The Aβ burden, neuropathological features, and cognitive ability in APP/PS1 mice were evaluated using ELISA kits, immunohistochemistry (IHC), and the Morris water maze (MWM) test. JWXG enhanced both the phagocytosis of EMR disorder-BV₂ cells (EMRD-BV₂) and increased EMR levels. Notably, these effects were significantly reversed in TREM2^-/- BV₂ cells. JWXG elevated TREM2 expression, adenosine triphosphate (ATP) levels, and microglial phagocytosis in APP/PS1 mice. Additionally, JWXG reduced Aβ-burden, neuropathological lesions, and cognitive deficits in APP/PS1 mice. In conclusion, JWXG promoted TREM2-induced EMR and enhanced microglial phagocytosis, thereby reducing Aβ deposition, improving neuropathological lesions, and alleviating cognitive deficits.
Drugs, Chinese Herbal/pharmacology* ; Microglia/drug effects* ; Phagocytosis ; Cognitive Dysfunction/drug therapy* ; Metabolic Reprogramming ; Animals ; Mice ; Cell Line ; Receptors, Immunologic/metabolism* ; Membrane Glycoproteins/metabolism* ; Signal Transduction ; Amyloid beta-Peptides/metabolism* ; Energy Metabolism

Objective: To analyze characteristics of iron-deficient blood donors, implement targeted interventions, and evaluate their effectiveness, thereby providing a reference for formulating blood donor recruitment and care strategies. Methods: Based on serum ferritin (SF) test results, the apheresis platelet donors were divided into the low SF group (n=90; 45 males and 45 females) and the normal SF group (n=651; 510 males and 141 females). The results of related indicators of the two groups were compared and analyzed. Interventions for the low SF group included extending the blood donation interval to at least 45 days (group A) and oral iron supplementation combined with the extended donation interval implemented in group A (group B). Pre-intervention and post-intervention SF results were compared. Results: For both male and female donors, serum iron levels were significantly lower in the low SF group than those of the normal SF group, while the levels of transferrin, unsaturated iron binding capacity (UIBC) and total iron binding capacity (TIBC) were higher in the low SF group compared to the normal SF group. Some indicators related to red blood cells showed changes, with more evident alterations in females than in males. Twenty-eight donors in group A and 39 donors in group B completed the study after intervention. SF value in group A was (18.32±8.09) μg/L at baseline and (26.21±17.30) μg/L after intervention. Similarly, SF value in group B was (15.87±7.69) μg/L at baseline and (26.24±15.55) μg/L after intervention. In both groups, SF values after intervention were significantly higher than baseline values. However, the magnitude of change did not significantly differ between groups A and B. Conclusion: Other related indicators in blood donors with low ferritin have also experienced some changes, suggesting that some blood donors may have entered the stage of iron-deficient erythropoiesis. Extending blood donation interval facilitates the recovery of iron storage in low-ferritin apheresis platelet donors. Blood stations should develop care strategies for apheresis platelet donors, including, at a minimum, the prolonged blood donation interval for donors with low ferritin.