Houpo Sanwutang， included in the Catalogue of Ancient Classical Prescriptions （Second Batch）， was first recorded in the Synopsis of Golden Chamber written by ZHANG Zhongjing from the Eastern Han dynasty and was modified by successive generations of medical experts. A total of 37 pieces of effective data involving 37 ancient Chinese medical books were retrieved from different databases. Through literature mining， statistical analysis， and data processing， combined with modern articles， this study employed bibliometrics to investigate the historical origin， composition， decoction methods， clinical application， and other key information. The results showed that the medicinal origin of Houpo Sanwutang was clearly documented in classic books. Based on the conversion of the measurements from the Han Dynasty， it is recommended that 110.4 g Magnolia Officinalis Cortex， 55.2 g Rhei Radix et Rhizoma， and 72 g Aurantii Fructus Immaturus should be taken. Magnolia Officinalis Cortex and Aurantii Fructus Immaturus should be decocted with 2 400 mL water first， and 1 000 mL should be taken from the decocted liquid. Following this， Rhei Radix et Rhizoma should be added for further decoction， and then 600 mL should be taken from the decocted liquid. A single dose of administration is 200 mL， and the medication can be stopped when patients restore smooth bowel movement. Houpo Sanwutang has the effect of moving Qi， relieving stuffiness and fullness， removing food stagnation， and regulating bowels. It can be used in treating abdominal distending pain， guarding， constipation， and other diseases with the pathogenesis of stagnated heat and stagnated Qi in the stomach. The above results provide reference for the future development and research of Houpo Sanwutang.

Integrin α _v β ₃ is overexpressed in various tumor cells and angiogenesis. To date, no drug has been proven to target it for therapy. A first-in-human study was designed to investigate the safety, pharmacokinetics, and dosimetry of ¹⁷⁷Lu-AB-3PRGD2, a novel integrin α _v β ₃-targeting radionuclide drug with an albumin-binding motif to optimize the pharmacokinetics. Ten patients (3 men, 7 women; aged 45 ± 16 years) with integrin α _v β ₃-avid tumors were recruited to accept ¹⁷⁷Lu-AB-3PRGD2 injection in a dosage of 1.57 ± 0.08 GBq (42.32 ± 2.11 mCi), followed by serial scans to obtain its dynamic distribution in the body. Safety tests were performed before and every 2 weeks after the treatment for 6-8 weeks. No adverse event over grade 3 was observed. ¹⁷⁷Lu-AB-3PRGD2 was excreted mainly through the urinary system, with intense radioactivity in the kidneys and bladder. Moderate distribution was found in the liver, spleen, and intestines. The estimated blood half-life was 2.85 ± 2.17 h. The whole-body effective dose was 0.251 ± 0.047 mSv/MBq. The absorbed doses were 0.157 ± 0.032 mGy/MBq in red bone marrow and 0.684 ± 0.132 mGy/MBq in kidneys. This first-in-human study of ¹⁷⁷Lu-AB-3PRGD2 treatment indicates its promising potential for targeted radionuclide therapy of integrin α _v β ₃-avid tumors. It merits further studies in more patients with escalating doses and multiple treatment courses.

Tianxiangdan (TXD), a traditional Chinese herbal remedy, demonstrates efficacy in mitigating myocardial ischemia-reperfusion (I/R)-induced damage. This study employed network pharmacology to evaluate the therapeutic targets and mechanisms of TXD in treating I/R. High-performance liquid chromatography-mass spectrometry (HPLC-MS) identified 86 compounds in TXD. Network pharmacological analysis predicted potential target genes and their modes of action. Cardiac function, ischaemic ST changes, lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD) activity, myocardial fiber, and infarct size were assessed using in vivo and in vitro I/R injury models. Estrogen receptor alpha (ERα) protein expression and estradiol (E2) levels were measured to confirm TXD's impact on estrogen levels and ERα expression. To examine if TXD reduces I/R injury through ERα, an AZD group (300 nmol·L^-1 AZD9496 and 15% TXD serum) was compared to a TXD group (15% TXD serum). The study hypothesized that TXD upregulates the ERα-mediated iron metamorphosis pathway. I/R injury-induced ferroptosis was identified using a Fer-1 group (1.0 μmol·L^-1 Fer-1 and 15% TXD serum) to elucidate the potential association between ferroptosis and ERα proteins. A DCFH-DA probe detected reactive oxygen species (ROS) and Fe²⁺, while Western blotting assessed target protein expression. Both in vitro and in vivo experiments demonstrated that TXD attenuated I/R injury by reducing elevated ST-segment levels, improving cardiac injury biomarkers (LDH, MDA, and SOD), alleviating pathological features, and preventing I/R-induced loss of cell viability in vitro. The effects and mechanisms of TXD on I/R injury-associated ferroptosis were investigated using I/R-induced H9c2 cells. The TXD group showed significantly decreased ROS and Fe²⁺ levels, while the AZ group (treated with AZD9496) exhibited increased levels. The TXD group demonstrated enhanced expression of ERα and glutathione peroxidase 4 (GPX4), with reduced levels of P53 protein and ferritin-heavy polypeptide 1 (FTH1). The AZ group exhibited contrasting effects on these expression levels. The literature indicated a novel connection between ERα and ferroptosis. TXD activates the ERα signaling pathway, promoting protection against I/R-induced myocardial cell ferroptosis. This study provides evidence supporting TXD use for myocardial ischemia treatment, particularly in older female patients who may benefit from its therapeutic outcomes.
Animals ; Ferroptosis/drug effects* ; Estrogen Receptor alpha/genetics* ; Myocardial Reperfusion Injury/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Male ; Mice ; Humans ; Mice, Inbred C57BL ; Estradiol/metabolism*

Ochratoxin A (OTA) is ubiquitous in the food and feed fields. It has strong hepatotoxicity and nephrotoxicity, seriously threatening the health of humans and animals. Enzymatic degradation of mycotoxins is considered to be a promising method to control mycotoxin contaminations. In this study, a new ochratoxin A amidohydrolase from Microbulbifer thermotolerans (MiADH) was obtained. After heterologous expression in Escherichia coli and purification, the recombinant protein was studied regarding the hydrolysis activity, hydrolysis products, enzymatic properties, and substrate binding mode. MiADH can degrade OTA into ochratoxin α (OTα) and phenylalanine, demonstrating a detoxifying ability. It demonstrated the best performance at 70 ℃ and pH 8.0, and Cu²⁺ had the strongest inhibitory effect on the activity of MiADH. MiADH with good thermal stability exhibited huge potential for industrial application. Rational design guided by three-dimensional structural models and substrate docking analysis revealed the important amino acids affecting substrate binding and obtained multiple mutants with improved activity. Among these mutants, V324A had the highest activity, which was 4.2-fold that of the wild type. The identification of MiADH enriches the ochratoxin A degradation enzyme library and provides a new candidate enzyme for the biological detoxification of ochratoxin A in the food and feed industry.
Amidohydrolases/chemistry* ; Ochratoxins/metabolism* ; Substrate Specificity ; Escherichia coli/metabolism* ; Recombinant Proteins/metabolism* ; Actinomycetales/genetics*

The types and prognosis of thyroid diseases in children are different from those in adults. Since the screening of congenital hypothyroidism in newborns，many kinds of the thyroid diseases with genetic defects in thyroid hormone production or action have been diagnosed and treated in newborn and infancy period. However，autoimmune and tumor related thyroid diseases in children may have typical clinical manifestations and can be diagnosed during the growth and development. Thyroid function plays a role in the nervous system and growth development of children，therefore screening，early diagnosis，and treatment of thyroid diseases in children outside of the neonatal period are equally important. This article reviews the recent advance in the types，causes，pathogenesis，clinical manifestations，diagnosis，and treatment of common thyroid diseases in children，in order to enhance the awareness of childhood thyroid diseases in clinical physicians.

Objective To investigate the characteristics of intestinal flora and its correlation with peripheral blood microinflammatory factors in patients with pulmonary tuberculosis complicated with diabetes mellitus(PTB-DM).Methods A total of 162 patients with PTB-DM admitted to the hospital from September 2022 to September 2024 were selected as the PTB-DM group,and another 150 healthy subjects who underwent physi-cal examinations during the same period in the hospital were selected as the control group.The clinical data of all research subjects was collected.The composition of intestinal flora of the research subjects was analyzed by using 16S rRNA gene sequencing technology.The levels of peripheral blood microinflammatory factors[inter-feron-γ(IFN-γ),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)]in all research subjects were detected.The clinical data,composition of intestinal flora and levels of microinflammatory factors of the PTB-DM group were compared with those of the control group.Spearman correlation analysis was used to analyze the correlation between the relative abundance of intestinal flora and the levels of peripheral blood microin-flammatory factors in patients with PTB-DM.Results The relative abundances of Bacteroidales and Clostridi-ales in the PTB-DM group were significantly lower than those in the control group,while the relative abun-dances of Enterobacterales and Actinobacteriales were significantly higher than those in the control group,and the differences were statistically significant(P<0.05).The levels of IFN-γ,IL-6 and TNF-α in the PTB-DM group were significantly higher than those in the control group,and the differences were statistically signifi-cant(P<0.05).The relative abundances of Bacteroidales and Clostridiales in the PTB-DM group were nega-tively correlated with the levels of IFN-γ,IL-6 and TNF-α.The relative abundances of Enterobacterales and Actinobacteriales were positively correlated with the levels of IFN-γ,IL-6 and TNF-α(all P<0.05).Conclu-sion There is a significant imbalance of intestinal flora in patients with PTB-DM,and the levels of microin-flammatory factors IFN-γ,IL-6 and TNF-α in peripheral blood are significantly increased,and are closely re-lated to the relative abundance of specific flora.

Objective To explore the expression changes of KIAA1199 and Linc00673 genes in non-small cell lung cancer patients before and after chemotherapy,and to further evaluate the potential value of these two genes as molecular markers in predicting chemotherapy efficacy.Methods A total of 58 patients with stage Ⅲ-ⅣNSCLC admitted to the Third Hospital of Shijiazhuang and Fengfeng General Hospital of North China Medical Health Group from August 2019 to August 2021 were selected.Peripheral blood PBMCs were collected from patients 2 days before treatment and after two cycles of treatment to detect the expression levels of KIAA1199 and Linc00673 genes.The chemotherapy efficacy of patients was statistically analyzed,and the value of KIAA1199 and Linc00673 genes as molecular markers in predicting chemotherapy efficacy was assessed using ROC curve analysis.Results After 2 cycles of chemotherapy,20 out of 58 patients showed disease progression,accounting for 34.48%.qPCR results showed no statistically significant difference in the expression levels of KIAA1199 and Linc00673 genes between progressed and non-progressed patients before treatment(P>0.05).After treatment,the expression levels of KIAA1199 and Linc00673 genes were significantly lower in non-progressed patients compared to progressed patients(P<0.01).ROC curve analysis showed that the AUC of combined detection was significantly higher than that of KIAA1199 gene and Linc00673 gene alone(Z=3.054,5.178,P<0.05).Conclusion In NSCLC patients undergoing chemotherapy,the expression of KIAA1199 and Linc00673 genes shows significant differences based on therapeutic efficacy,with KIAA1199 being more suitable as a biomarker for predicting chemotherapy efficacy.

The key pathogenesis of coronary heart disease （CHD） is spleen deficiency and phlegm stasis， and dysfunctional high-density lipoprotein （dys-HDL） may be the biological basis for the occurrence of CHD due to spleen deficiency and phlegm stasis. Considering the biological properties and effects of high-density lipoprotein （HDL）， it is believed that the structure and components of HDL are abnormal in the state of spleen deficiency which led to dys-HDL； and dys-HDL contributes to the formation of atherosclerotic plaques through two major pathways， namely， mediating the dysfunction of endothelial cells and mediating the foaminess of macrophages and smooth muscle cells， thus triggering the development of CHD. It is also believed that dys-HDL is a microcosmic manifestation and a pathological product of spleen deficiency， and spleen deficiency makes foundation for the production of dys-HDL； dys-HDL is also an important biological basis for the phlegm-stasis interactions in CHD. The method of fortifying spleen， resolving phlegm， and dispelling stasis， is proposed as an important principle in the treatment of CHD by traditional Chinese medicine， which can achieve the therapeutic purpose by affecting the changes in the structure and components of dys-HDL， thus revealing the scientific connotation of this method， and providing ideas for the diagnosis and treatment of CHD by traditional Chinese medicine.

Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Objective To explore the machine learning model and risk factor analysis for hospital infection caused by carbapenem-resistant enterobacteriaceae(CRE).Methods The clinical data of totally 451 patients infected with extended-spectrum β-lactamases(ESBL)producing Enterobacteriaceae treated in the hospital from 2018 to 2022 were retrospectively collected.The patients were divided into CRE group(115 cases)and sensitive group(336 cases)according to the susceptibility of carbapenem.Four machine learning methods in-cluding Logistic regression analysis,random forest,support vector machine,and neural network were used to build prediction models and receiver operating characteristic curve was used to evaluate.Based on the predic-tion model with the best performance,risk factors for CRE infection were analyzed.Results Random forest model had the best performance,with the area under the curve of 0.952 3.The risk factors for predicting CRE infection by the random forest model included 15 clinical data items,namely fever for more than 3 days,cere-bral injury,drainage fluid sample,trunk surgery,first-level or special-level nursing,ICU treatment,procalcito-nin,anti-anaerobic bacteria,the use of third-generation cephalosporins,age,pre-albumin,creatinine,white blood cell count,and albumin.Conclusion The CRE prediction model developed in this study has good predic-tive value and the risk factors have guiding significance for the early prevention and treatment of CRE infec-tion in clinical practice.