ObjectiveTo investigate the effects of Huangqi Jianzhongtang （HQJZ） on macrophage polarization and fat consumption in cancer cachexia （CC） mice. MethodsUltra-performance liquid chromatography-quadrupole/electrostatic field Orbitrap high-resolution mass spectrometry （UPLC-Q-Orbitrap HRMS） was used to control the quality of HQJZ. （1） In vitro experiment： HQJZ-containing serum was prepared， and the optimal concentration was determined by cytotoxicity assay. Mouse monocyte-derived macrophages （RAW264.7） were cultured and randomly divided into six groups， including a blank group， a classically activated macrophages （M1） group， an alternatively activated macrophages （M2） group， a HQJZ + blank group， a HQJZ+M1 group， and a HQJZ + M2 group. The relative expression of macrophage marker genes CD86， inducible nitric oxide synthase （iNOS）， CD206， and arginase-1 （Arg1） was detected by real-time quantitative polymerase chain reaction （Real-time PCR ）. （2） In vivo experiment： Thirty-two BALB/c mice were randomly divided into a control group， a model group， a medroxyprogesterone acetate （MPA） group， and a HQJZ group. Except for the control group， the other mice were injected with CT-26 colon cancer cells to establish a CC model. Mice in the MPA and HQJZ groups were given MPA （0.13 g·kg^-1·d^-1） or HQJZ （13.13 g·kg^-1·d^-1） by gavage， respectively， while mice in the control and model groups were given an equal volume of saline by gavage， with interventions continued for 10 d. Real-time PCR was used to detect the expression of macrophage markers （iNOS， Arg1， CD86， CD206） and fat browning-related genes uncoupling protein 1 （UCP1） and peroxisome proliferator-activated receptor γ （PPARγ） in epididymal adipose tissue. Western blot （WB） was used to detect protein expression levels of UCP1 and PPARγ. Micro-computed tomography （micro-CT） was used to measure residual fat volume， and hematoxylin-eosin （HE） staining was used to assess fat browning and calculate pathological scores. ResultsIn vitro， the dominant effective concentration of HQJZ-containing serum was 12.5%. Real-time PCR results showed that， compared with the blank group， Arg1 expression decreased in the HQJZ+blank group （P<0.05）， CD206 showed a downward trend without statistical significance， while iNOS and CD86 expression were significantly increased （P<0.05）. Compared with the M1 group， Arg1 and CD206 expression decreased in the HQJZ+M1 group （P<0.05）. Compared with the M2 group， CD206 expression decreased in the HQJZ+M2 group （P<0.05）， CD86 expression increased significantly （P<0.01）. In vivo， Real-time PCR results showed that， compared with the control group， CD86 and CD206 expression levels were significantly increased in the model group （P<0.01）. Compared with the model group， CD206 expression in the MPA group was significantly decreased （P<0.01）. In the HQJZ group， CD206 was significantly decreased （P<0.01）. WB results showed that， compared with the model group， protein expression of UCP1 and PPARγ was significantly reduced in the HQJZ group （P<0.05， P<0.01）. micro-CT results showed that the total white fat volume in the HQJZ group was greater than that in the model group （P<0.05）. HE staining results showed that pathological scores in the HQJZ group were lower than those in the model group （P<0.05）. ConclusionHQJZ may inhibit white adipose tissue browning by promoting macrophage M1 polarization and suppressing M2 polarization， thereby delaying fat consumption in CC mice.

OBJECTIVE: To study incident and clinical characteristics of the coronary microcirculation dysfunction (CMD) in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI) by myocardial contrast echocardiography (MCE) and to explore the predictive value of CMD for in-hospital acute heart failure event. METHODS: One hundred and forty five patients with AMI who had received PCI and completed MCE during hospitalization in Peking University People' s Hospital from November 2015 to July 2021 were enrolled in our study. The patients were divided into CMD group and normal group according to the coronary microcirculation status detected by MCE. Clinical data and MCE data of the two groups were collected and analyzed. The acute heart failure event during hospitalization was described. A multivariate Logistic regression model was built to analyze the risk of acute heart failure in patients with CMD. A receiver operating characteristic (ROC) curve was drawn to evaluate the value of CMD in predicting acute heart failure event. RESULTS: CMD detected by MCE occurred in 87 patients (60%). Compared with normal group, patients with CMD had higher troponin I (TnI) peak level [52.8 (8.1, 84.0) μg/L vs. 18.9 (5.7, 56.1) μg/L, P=0.005], poorer Killip grade on admission (P=0.030), different culprit vessel (P < 0.001) and more patients had thrombolysis in myocardial infarction (TIMI) flow pre-PCI less than grade 3 in culprit vessel (65.1% vs. 43.1%, P=0.025). Meanwhile, patients with CMD had poorer left ventricular ejection fraction (LVEF) [52% (43%, 58%) vs. 61% (54%, 66%)], poorer global longitudinal strain (GLS) [-11.2% (-8.7%, -14.0%) vs.-13.9% (-10.8%, -17.0%)] and worse wall motion score index (WMSI) (1.58±0.36 vs. 1.25± 0.24) (P all < 0.001). Acute left heart failure happened in 13.8% of the CMD patients, which were significant higher than that in the patients with normal coronary microcirculation perfusion (1.7%, P=0.013). After correcting for the culprit vessel, the TIMI flow pre-PCI in the culprit vessel and the peak TnI value, the risk of acute left heart failure in the patients with CMD was still high (OR=9.120, 95%CI: 1.152-72.192, P=0.036). The area under ROC curve (AUC) was 0.677 (95%CI: 0.551-0.804, P=0.035). CONCLUSION The incidence of CMD detected by MCE in patients with AMI post-PCI was 60%. Patients with CMD have a higher risk of acute left heart failure during hospitalization.
Humans ; Heart Failure/physiopathology* ; Microcirculation ; Percutaneous Coronary Intervention/adverse effects* ; Myocardial Infarction/complications* ; Male ; Female ; Hospitalization ; Middle Aged ; Aged ; Echocardiography ; Coronary Circulation ; Predictive Value of Tests ; Troponin I/blood*

Combined with elastic network model (ENM), the perturbation response scanning (PRS) has emerged as a robust technique for pinpointing allosteric interactions within proteins. Here, we proposed the PRS analysis of drug-target networks (DTNs), which could provide a promising avenue in network medicine. We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework, for drug repurposing of multiple sclerosis (MS). First, the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes. Then, based on topological analysis and functional annotation, the neurotransmission module was identified as the "therapeutic module" of MS. Further, perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis, giving a list of repurposable drugs for MS. Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of serotonin 2B receptor (HTR2B). Finally, we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex. These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS. As a useful systematic method, our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.

Objective:To assess the value of serum tumor specific protein 70 (SP70) for prognostic stratification in acute myeloid leukemia (AML).Methods:A cohort study design was adopted. 129 newly diagnosed AML patients from September 2022 to January 2024 at the Hematology Department of the First Affiliated Hospital of Nanjing Medical University were included, as well as a control group consisted of 120 healthy individuals and 7 cases with benign hematologic diseases during the same period (total 127 cases). Clinical data were collected from Electronic Medical Records. According to the 2023 edition of the Chinese Leukemia Diagnosis and Treatment Guidelines, AML patients with good or moderate prognosis were categorized as low-to-intermediate risk, while those with poor prognosis were high-risk group. Univariate and multivariate logistic regression analyses were used to identify variables significantly associated with AML prognostic risk. ROC analysis was used to evaluate diagnostic performance. A nomogram for predicting patient prognostic risk was constructed by R 4.0.2 software, and the internal validation was performed using bootstrapping.Results:Among 129 AML patients, there were 71 males (55.0%) and 58 females (45.0%), with 42 (32.6%) classified as high-risk and 87 (67.4%) as low-intermediate risk. The high-risk group had a significantly higher median age [62 (48, 67) years] compared to the low-intermediate risk group [50 (35, 63) years, Z=-2.381, P=0.017], and a significantly higher proportion of males (30 patients, 71.4%) compared to the low-intermediate risk group (41 patients, 47.1%, χ 2=6.760, P=0.009). Multivariate logistic regression analysis indicated that serum SP70 ( OR=2.54, 95% CI: 1.68-3.84, P<0.001), hemoglobin (HB) ( OR=0.96, 95% CI: 0.93-0.99, P<0.05), and bone marrow blast (BM blast) ( OR=1.07, 95% CI: 1.02-1.13, P<0.05) were independent risk factors for high-risk prognosis in AML patients. ROC analysis showed that the area under the curve (AUC) for SP70 predicting high-risk patients was 0.908 (cut-off value of 5.74 ng/ml, 95% CI: 0.845-0.952, sensitivity 90.5%, specificity 82.8%). The combined model of serum SP70, HB, and BM blasts had an AUC of 0.931 (95% CI: 0.890-0.973); C-index=0.925 (95% CI: 0.876-0.963),with no statistically significant difference compared to serum SP70 alone ( Z=1.693, P>0.05). Conclusion:Serum SP70 may be a promising non-invasive molecular biomarker for prognostic stratification in AML.

Objective:To analyze the epidemiological and clinical characteristics of patients with brucellosis.Methods:Medical records of confirmed brucellosis patients ( n = 101) were collected from January 2015 to December 2022 at the First Affiliated Hospital of Nanjing Medical University. Patients were divided into acute phase group (≤3 months, n = 89) and non acute phase group (> 3 months, n = 12) according to the course of the disease. The epidemiological characteristics, clinical symptoms, laboratory indicators, treatment plan and curative effect of the patients were analyzed retrospectively. Results:Data of a total of 101 cases of brucellosis were collected, including 72 males and 29 females. The disease occurred throughout the year, with summer (June to August) being the peak period (43.56%, 44/101); 72.28% (73/101) cases had a clear history of contact with animal. Ninety-two point zero eight percent (93/101) of the patients visited the Department of Infectious Diseases for the first time. Clinical manifestations included fever, accounting for 82.18% (83/101), chills accounting for 36.63% (37/101), backache accounting for 33.66% (34/101), night sweats accounting for 22.77% (23/101), and arthralgia accounting for 20.79% (21/101). The symptoms of backache (75.00%, 9/12) and arthralgia (41.67%, 5/12) were more common in patients in the non acute phase group than those of the acute phase group [28.09% (25/89), 17.98% (16/89), P < 0.05]. The most common laboratory test abnormal items were elevated C-reactive protein (CRP, 68.32%, 69/101), erythrocyte sedimentation rate (ESR, 61.39%, 62/101), aspartate aminotransferase (AST, 58.42%, 59/101), and alanine aminotransferase (ALT, 48.51%, 49/101). Elevated ESR (66.29%, 59/89) was more common in patients in the acute phase group than that of the non acute phase group [25.00 (3/12), χ 2 = 7.48, P = 0.006]. All patients were treated with a combination therapy, with a recovery rate of 100.00% (101/101). Conclusions:Brucellosis patients are more common in males, with a higher incidence in summer and often accompanied by a history of contact with animal. The clinical manifestations are diverse and non-specific.

Objective:To analyze the ultrasonographic measurements of inferior vena cava (IVC) and abdominal aorta in healthy full-term neonates throughout the early postnatal period.Methods:Prospective observational study was conducted. A total of 132 healthy full-term neonates, who were born at the Kunshan First People′s Hospital between May 1 st and August 30 th, 2023, were enrolled as the study subjects. Two-dimensional and M-mode ultrasonography were used to measure the maximum and minimum diameters of the IVC and abdominal aorta in the early postnatal period. The IVC collapsibility index, the ratio of maximum IVC diameter to abdominal aorta diameter, and the ratio of minimum IVC diameter to abdominal aorta diameter were calculated. These neonates were stratified by gender, birth mode, gestational age and birth weight (<3 000 or ≥3 000 g), and independent sample t-test or Kruskal-Wallis H test was used to compare the ultrasonography measurements by different groups. Results:Among the 132 neonates, 81 were males, with a gestational age of (39.2±1.0) weeks, and a birth weight of (3 326±409) g. There were no significant statistical differences in the the maximum and minimum diameters of the IVC and abdominal aorta assessed by both two-dimensional and M-modes between the first and second days (all P>0.05). Additionally, no statistical differences were observed in the ultrasonographic measurements among neonates of different sexes, birth modes, and gestational ages (all P>0.05); but there were statistically differences between the group with birth weight of <3 000 g and the group with birth weight of ≥3 000 g (all P<0.05). There were no statistically differences in IVC collapsibility index, the ratio of the maximum diameter of IVC to the diameter of abdominal aorta, and the ratio of the minimum diameter of IVC to the diameter of abdominal aorta between the group with birth weight of <3 000 g and the group with birth weight of≥3 000 g (all P>0.05). Conclusions:The diameters of the IVC and abdominal aorta in healthy full-term neonates during the early postnatal period are correlated with birth weight. The IVC collapsibility index and the ratio of IVC diameter to abdominal aorta diameter are unrelated to birth weight and can be used to assess newborn blood volume or right cardiac preload.

Objective:To assess the value of serum tumor specific protein 70 (SP70) for prognostic stratification in acute myeloid leukemia (AML).Methods:A cohort study design was adopted. 129 newly diagnosed AML patients from September 2022 to January 2024 at the Hematology Department of the First Affiliated Hospital of Nanjing Medical University were included, as well as a control group consisted of 120 healthy individuals and 7 cases with benign hematologic diseases during the same period (total 127 cases). Clinical data were collected from Electronic Medical Records. According to the 2023 edition of the Chinese Leukemia Diagnosis and Treatment Guidelines, AML patients with good or moderate prognosis were categorized as low-to-intermediate risk, while those with poor prognosis were high-risk group. Univariate and multivariate logistic regression analyses were used to identify variables significantly associated with AML prognostic risk. ROC analysis was used to evaluate diagnostic performance. A nomogram for predicting patient prognostic risk was constructed by R 4.0.2 software, and the internal validation was performed using bootstrapping.Results:Among 129 AML patients, there were 71 males (55.0%) and 58 females (45.0%), with 42 (32.6%) classified as high-risk and 87 (67.4%) as low-intermediate risk. The high-risk group had a significantly higher median age [62 (48, 67) years] compared to the low-intermediate risk group [50 (35, 63) years, Z=-2.381, P=0.017], and a significantly higher proportion of males (30 patients, 71.4%) compared to the low-intermediate risk group (41 patients, 47.1%, χ 2=6.760, P=0.009). Multivariate logistic regression analysis indicated that serum SP70 ( OR=2.54, 95% CI: 1.68-3.84, P<0.001), hemoglobin (HB) ( OR=0.96, 95% CI: 0.93-0.99, P<0.05), and bone marrow blast (BM blast) ( OR=1.07, 95% CI: 1.02-1.13, P<0.05) were independent risk factors for high-risk prognosis in AML patients. ROC analysis showed that the area under the curve (AUC) for SP70 predicting high-risk patients was 0.908 (cut-off value of 5.74 ng/ml, 95% CI: 0.845-0.952, sensitivity 90.5%, specificity 82.8%). The combined model of serum SP70, HB, and BM blasts had an AUC of 0.931 (95% CI: 0.890-0.973); C-index=0.925 (95% CI: 0.876-0.963),with no statistically significant difference compared to serum SP70 alone ( Z=1.693, P>0.05). Conclusion:Serum SP70 may be a promising non-invasive molecular biomarker for prognostic stratification in AML.

OBJECTIVE To investigate the current situation of pharmaceutical management in compact medical consortium of Guangdong province， and to provide decision-making basis for promoting the high-quality construction and sustainable development of the provincial medical consortium. METHODS A self-designed questionnaire was used to select 50 compact medical consortiums in Guangdong province. The survey was answered by the heads of the pharmacy department of the general hospitals. The survey covered the basic scale of the consortium， the appointment of chief pharmacists， the implementation of pharmaceutical management and pharmaceutical care homogenization within the consortium， the difficulties in promoting the homogenization， and the expected provincial support. Descriptive statistical analysis was performed on the survey results. RESULTS A total of 50 questionnaires were collected， and the effective recovery rate was 100%. There were 16 chief pharmacists （32.00%） in charge of the pharmacy department of the general hospital in the medical consortium. Thirty-seven medical consortiums （74.00%） had established a drug supply support system within the consortium， 35 medical consortiums （70.00%） had carried out pharmaceutical management and coordination work within the medical consortium， 23 medical consortiums （46.00%） had established a clinical medication guidance system， 25 medical consortiums chenwenying2016@163.com （50.00%） had established a bidirectional communication mechanism， and only 8 medical consortiums （16.00%） had developed new models of pharmaceutical care. At present， the difficulties in promoting the homogenization of pharmaceutical management and pharmaceutical care within the medical consortium were mainly found in three aspects： the wide gap in management level of each member unit， the lack and uneven level of pharmaceutical personnel， and insufficient policy support and implementation. Most medical consortiums hoped that relevant departments could promote the homogenization of pharmaceutical work by holding special training courses or special supervision. CONCLUSIONS At present， the compact medical consortium in Guangdong province has achieved initial results in the implementation of the chief pharmacist system， the homogenization of pharmaceutical management and pharmaceutical care. However， it is still necessary to improve the coverage of chief pharmacist appointments in the medical consortium， implement the homogenization of pharmaceutical management， and accelerate the homogenization process of pharmaceutical care.

Alzheimer′s disease (AD) is a neurodegenerative disorder. In the past few decades, the exact mechanisms underlying the onset of the disease have remained unclear, and treatment options are still lacking. Due to the inability of two-dimensional cell and animal models to fully simulate the pathogenesis of AD, there have been shortcomings in clinical trials of new drugs. The development of organoids and organ-on-a-chip technologies has improved the dilemma of AD research, providing reliable in vitro research models for studying pathogenic mechanisms and drug screening. This article elaborates on the applications and progress of organoids and organ-on-a-chip in AD modeling, pathogenesis, and drug development, and discusses the current limitations of organoids and organ-on-a-chip and their future perspectives.

Microcephaly is a common pediatric neurodevelopmental disorder with complex etiology. In recent years, with the development of brain organoid technology, there has been rapid progress in understanding the pathogenesis and treatment strategies of microcephaly using this technology. This article elucidates the advantages of brain organoids over traditional experimental models, reviews the research progress of brain organoid technology in disease modeling and drug screening for various causes of microcephaly, and discusses the limitations and future prospects of brain organoids.