BACKGROUND:Spleen has the functions of blood storage,hematopoiesis,and immunity.With the increase of age,the structural degeneration and functional decline of spleen lead to the impairment of immune system function,thus accelerating the aging process of the body.The treatment of spleen aging in tree shrews with highly active umbilical cord mesenchymal stem cells has not been reported. OBJECTIVE:To explore the intervention effect and mechanism of highly active umbilical cord mesenchymal stem cells on spleen aging in tree shrews. METHODS:Highly active umbilical cord mesenchymal stem cells were isolated,cultured,and obtained from the umbilical cord tissue of newborn tree shrews by caesarean section.The differentiation abilities of adipogenesis,osteogenesis,and chondrogenesis were detected by three-line differentiation kit.Cell cycle and surface markers were detected by flow cytometry.The second generation of highly active umbilical cord mesenchymal stem cells were transfected with Genechem Green Fluorescent Protein with infection complex values of 100,120,140,160,180,and 200,respectively,to screen the best transfection conditions.After transfection,the fourth generation of highly active umbilical cord mesenchymal stem cells was injected into the tail vein of tree shrews in the elderly treatment group.The young control group and the aged model group were not given special treatment.After 4 months of treatment,the spleen tissue was taken and the structure of the spleen was observed by hematoxylin-eosin staining.β-Galactosidase staining was used to detect the activity of aging-related galactosidase.Immunohistochemical staining was used to detect the expression levels of p21 and p53 proteins.Ki67 and PCNA immunofluorescence staining was used to detect cell proliferation activity.Immunofluorescence staining was used to detect the expression levels of spleen autophagy protein molecules Beclin 1 and APG5L/ATG5.Reactive oxygen species fluorescence staining was used to detect the content of reactive oxygen species in spleen tissue.CD3 immunofluorescence staining was used to detect the change of the proportion of total T lymphocytes.The secretion levels of interleukin 1β and transforming growth factor β1 in spleen were detected by enzyme linked immunosorbent assay.The distribution of highly active umbilical cord mesenchymal stem cells labeled with green fluorescent protein in spleen tissue was observed by DAPI double staining of nucleus. RESULTS AND CONCLUSION:(1)Highly active umbilical cord mesenchymal stem cells grew in a short spindle shape with fish-like growth,with a large proportion of G0/G1 phase,and had the potential to differentiate into adipogenesis,osteogenesis,and chondrogenesis.(2)Multiplicity of infection=140 and transfection for 72 hours were the best conditions for labeling tree shrews highly active umbilical cord mesenchymal stem cells with Genechem Green Fluorescent Protein.(3)Compared with the aged model group,in the aged treatment group,the spleen tissue cells of tree shrews were arranged closely,and the area of white pulp was increased(P<0.01);the boundary between red pulp and white pulp was clear;the proportion of germinal centers did not show statistically significant difference(P>0.05).The activity level of galactosidase related to spleen tissue aging was decreased(P<0.001),and the expression levels of aging protein molecules p21 and p53 were down-regulated(P<0.001).The expression levels of proliferation-related molecules Ki67 and PCNA were up-regulated(P<0.001,P<0.05);expression levels of autophagy-related molecules Beclin 1 and APG5L/ATG5 were up-regulated(P<0.001),and the content of reactive oxygen species decreased(P<0.001),and the proportion of CD3+T cells increased(P<0.05).The secretion level of interleukin 1β in the aging-related secretion phenotype decreased(P<0.001);no significant difference was found in transforming growth factor β1 level(P>0.05).Compared with the young control group,the above indexes were significantly different in the elderly treatment group(P<0.05).(4)Green fluorescent cells labeled with green fluorescent protein were observed in spleen tissue of tree shrews the elderly treatment group by frozen tissue section observation.The results show that intravenous infusion of highly active umbilical cord mesenchymal stem cells can migrate to spleen tissue,inhibit the production of reactive oxygen species,down-regulate the expression of aging-related proteins,induce autophagy,promote cell proliferation,reduce chronic inflammation,and then improve the structure and function of spleen tissue.

The patient was a girl aged 10 years and 10 months, with weakness, pale complexion, and rash as the initial presentation. She had the manifestations of anemia, thrombocytopenia, hematuria-proteinuria with renal insufficiency, hypocomplementemia, polyserositis, and positive anti-nuclear antibody and anti-dsDNA antibody. The girl was initially diagnosed with systemic lupus erythematosus and lupus nephritis. She demonstrated a suboptimal response to methylprednisolone pulse therapy, intravenous immunoglobulin administration, and therapeutic plasma exchange. She had persistent anemia, thrombocytopenia, abnormal renal function, elevated lactate dehydrogenase, decreased complement factors H and I, increased antibodies to C3 converting enzyme, and normal ADAMTS13 activity. She was diagnosed with complement-mediated hemolytic thrombotic microangiopathy secondary to systemic lupus erythematosus. The patient's condition improved after treatment with two doses of eculizumab (600 mg per dose). Patients with systemic lupus erythematosus complicated by thrombotic microangiopathy often have a severe disease course and poor prognosis; therefore, early recognition and aggressive intervention are crucial for improving outcomes.
Humans ; Female ; Lupus Erythematosus, Systemic/drug therapy* ; Thrombotic Microangiopathies/etiology* ; Antibodies, Monoclonal, Humanized/therapeutic use* ; Child

Anxiety disorder is a major symptom of autism spectrum disorder (ASD) with a comorbidity rate of ~40%. However, the neural mechanisms of the emergence of anxiety in ASD remain unclear. In our study, we found that hyperactivity of basolateral amygdala (BLA) pyramidal neurons (PNs) in Shank3 InsG3680 knock-in (InsG3680^+/+) mice is involved in the development of anxiety. Electrophysiological results also showed increased excitatory input and decreased inhibitory input in BLA PNs. Chemogenetic inhibition of the excitability of PNs in the BLA rescued the anxiety phenotype of InsG3680^+/+ mice. Further study found that the diminished control of the BLA by medial prefrontal cortex (mPFC) and optogenetic activation of the mPFC-BLA pathway also had a rescue effect, which increased the feedforward inhibition of the BLA. Taken together, our results suggest that hyperactivity of the BLA and alteration of the mPFC-BLA circuitry are involved in anxiety in InsG3680^+/+ mice.
Animals ; Prefrontal Cortex/metabolism* ; Basolateral Nuclear Complex/metabolism* ; Mice ; Anxiety/metabolism* ; Nerve Tissue Proteins/genetics* ; Male ; Gene Knock-In Techniques ; Pyramidal Cells/physiology* ; Mice, Transgenic ; Neural Pathways/physiopathology* ; Mice, Inbred C57BL ; Microfilament Proteins

Objective To evaluate the efficacy and safety of systemic thrombolysis(ST)and standard anticoagulation(SA)in the treatment of lower extremity fracture complicated with distal deep vein thrombosis(DDVT).Methods We retrospectively analyzed the clinical data of 60 patients with lower extremity fracture complicated with DDVT treated from January 2021 to December 2023.When the lower limb venography indicated a calf thrombus burden score ≥3 points,a retrievable inferior vena cava filter(IVCF)was successfully placed in the healthy femoral vein before orthopedic surgery.The patients who received further anticoagulant or thrombolytic therapy after surgery were allocated into a ST group(n=30,urokinase ST and SA)and a SA group(n=30,only SA).The two groups were compared in terms of calf thrombus burden score,thrombus dissolution rate,IVCF placement time,IVCF retrieval rate,intercepted thrombi,hemoglobin level,platelet count,D-dimer level,and complications.Results There was no statistically significant difference in the calf thrombus burden score between the two groups before treatment(P=0.431).However,after treatment,the scores in both groups decreased(both P<0.001),with the ST group showing lower score than the SA group(P=0.002).The thrombus dissolution rate in the ST group was higher than that in the SA group(P<0.001).There was no statistically significant difference in the IVCF placement time between the two groups(P=0.359),and the IVCF retrieval rate was 100% in both groups.The ST group had fewer intercepted thrombi than the SA group(P=0.002).There was no statistically significant difference in hemoglobin level(P=0.238),platelet count(P=0.914),or D-dimer level(P=0.756)between the two groups before treatment.However,after treatment,both groups showed an increase in platelet count(both P<0.001)and a decrease in D-dimer level(both P<0.001).There was no statistically significant difference in the occurrence of complications between the two groups(P=0.704).Conclusions Both SA and ST demonstrate safety and efficacy in the treatment of lower extremity fractures complicated with DDVT,serving as valuable options for clinical application.Compared with SA,ST not only enhances the thrombus dissolution in the calf but also mitigates the risk of thrombosis associated with IVCF.
Humans ; Venous Thrombosis/therapy* ; Retrospective Studies ; Thrombolytic Therapy/methods* ; Male ; Female ; Middle Aged ; Fractures, Bone/complications* ; Lower Extremity/injuries* ; Anticoagulants/therapeutic use* ; Aged ; Treatment Outcome ; Adult

Objective To analyze risk factors for sleep disorders in patients with chronic heart failure(CHF)and construct a nomogram prediction model.Methods Using simple random sampling,306 hospital-ized CHF patients meeting inclusion criteria were enrolled from four Grade A tertiary hospitals in Guangxi Zhuang Autonomous Region(two in Nanning,one each in Yulin and Guilin)between March 2023 and March 2024.LASSO regression analysis was initially employed for variable screening,followed by logistic regression to identify predictive variables for constructing the nomogram model.Model validation and performance evalua-tion were conducted using receiver operating characteristic(ROC)curves,calibration curves,and clinical decision curves,with internal validation performed through Bootstrap resampling(1 000 iterations).Results The incidence of sleep disorders among the 306 patients was 57.5%(176/306).Logistic regression analysis identified eight independent risk factors for sleep disorders in CHF patients(P＜0.05):age,education level,monthly house-hold income per capita,NYHA cardiac function classification,number of comorbidities,triglyceride levels,ano-rexia,and anxiety.The model demonstrated good discrimination for the AUC of 0.91(95%CI:0.77-0.88)and calibration consistency.Conclusion The prediction model established in this study shows good predictive performance,serving as a valuable reference for healthcare providers to early identify sleep disorders and im-plement preventive care strategies in patients with CHF.

The term yin excess originated in the Huang Di Nei Jing, which refers to the phenomenon of "heavy yin" when wind pathogens invades the human body and defensive qi enters the yin part of the human body. Later doctors have played a role in yin excess. Theoretically, yin and yang are out of balance in the human body, and yin is too much and yang is not enough, which is the process of physiological transformation to pathology; from the diagnosis point of view, patients with yin deficiency have less pulse and more blood; from the clinical manifestations, patients with yin excess appear cold from the back, hands and feet cold reverse; from the point of view of treatment, bitter cold products can cause yin excess. Modern research specifies yin as phlegm, dampness, stasis and other pathological products, and emphasize the relation between yin excess and yang deficiency. Yin excess includes pathological factors such as phlegm stasis cold, external cold straight in the liver wood, set in the hypochasm, resulting in mass; or overthinking and cold drink injury spleen, phlegm turbidiousness, long and hard phlegm forming lumps, thus resulting yin excess; or it may deplete the yang energy of the heart, leading to neglect of the warming function and stagnation of blood stasis; or if the kidney yang is deficient and the body lacks warmth, and there is no true yang in the ridge, then the wood will sink and congest blood stasis; the above etiology and pathogenesis lead to the occupation of yin pathogens, resulting in liver cancer. The treatment methods include liver cold turbidizing, warming liver and dispelling cold, with Wuzhuyu Decoction; spleen-deficiency phlegm production, the treatment should be warm the middle and resolving the phlegm, with Linggui Zhugan Decoction and Zhenwu Decoction; Yang deficiency and stasis, the treatment should warm kidney to remove blood stasis, with Poyu Decoction.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To establish a method for the determination of lorlatinib in human plasma by two-dimensional high performance liquid chromatography.Methods In the two-dimensional high performance liquid chromatography method,one-dimensional column SX1E-1A(50 mm × 3.5 mm,5 μm)and two-dimensional column SCB-C18(125 mm × 4.6 mm,5 μm)were used with flow rates of 0.8 mL·min-1 and 1.0 mL·min-1,respectively.The column temperature was 40 ℃,The UV detection wavelength was 317 nm,and the sample size was 500 μL.This study investigated the specificity,standard curve and minimum quantification limit,precision and recovery rate,as well as stability of the method.Results The concentration of lolatinib in human plasma showed a good linear relationship in the range of 11.72-1 018.98 ng·mL-1,and the regression equation was y=944.50x-588.90(R2=0.999 7).The minimum limit of quantification was 11.72 ng·mL-1.The extraction recovery rates of the three quality control samples were 97.61％-99.86％,and the intra-day and inter-day precisions were less than 5.29％,indicating that the detection performance of the method was good.Conclusion The method has the characteristics of good stability,high sensitivity and strong anti-interference ability,and is suitable for the determination of loratinib in human plasma.

Objective To compare the accuracy of the original-mirror alignment algorithm and a landmark-indepen-dent method in constructing the midsagittal plane(MSP)of the cone beam computed tomography in patients with facial deformities,so as to provide a theoretical basis for symmetric analysis.Methods The study was approved by the hospi-tal ethics committee.Cone beam computed tomography data of 30 patients with facial deformities were obtained,and the output was saved in DICOM format.The scan data were imported into Mimics 21.0;after segmentation,three-dimension-al(3D)skull models were reconstructed.Furthermore,the 3D scan data of skulls were transformed into mirror skull models using Geomagic Studio 2014 reverse engineering software.The MSP of each skull was generated using both the original-mirror alignment algorithm and the landmark-independent method.Original-mirror alignment algorithm:the original skull model and its mirror model were combined,and the new data to calculate the MSP(S1)of the original data in Geomagic Studio 2014 were obtained.Landmark-independent method:the following anatomical landmarks were deter-mined using Mimics 21.0:nasion(N),crista galli(CG),sella(S),basion(Ba),vomer(V),posterior nasal spine(PNS),in-cisive foramen(IF),and anterior nasal spine(ANS).The MSP(S2)of best fit was then found by minimizing the mean square distance of these eight anatomical landmarks to a plane in Geomagic Studio 2014.The results of the S1 and S2 models constructed using the original-mirror alignment algorithm and the landmark-independent method,respectively,were scored subjectively by five senior maxillofacial surgeons,and a paired t-test was performed for the two groups.The internal consistency analysis was performed based on secondary experiments to verify the repeatability of the expert evaluation method.Results The average scores of the S1 and S2 models were 65.73 and 75.90,respectively.The aver-age score of the model constructed using the landmark-independent method was significantly higher than that of the model constructed using the original-mirror alignment algorithm(P＜0.01).Furthermore,the results of the internal con-sistency analysis showed that the expert evaluation method had good reliability and validity.Conclusion In patients with facial deformities,the MSP constructed using the landmark-independent method is superior to that constructed us-ing the original-mirror alignment algorithm.This study provides a theoretical basis for maxillofacial symmetry analysis in clinical settings and is clinically feasible.