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*

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*

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.

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.

Objective:To analyze the prognosis,clinicopathological characteristics,and genetic mutation features of patients with very low-and low-risk gastrointestinal stromal tumors(GISTs).Methods:A retrospective data collection of 433 patients with very low-and low-risk GISTs,diagnosed by pathology after surgical or endoscopic resection at Tianjin Medical University Cancer Institute&Hospital,was conduc-ted to analyze clinical pathology and prognosis.Results:Compared with low-risk GIST,a higher proportion of patients with very low-risk GIST had gastric GISTs,a Ki-67 index≤3%,and 0-1 mitotic indexes/5 mm2,whereas the proportion of patients with small intestinal GIST was low(all P<0.05).Genetic testing was performed in 118 patients,and there was no significant difference in the mutation types and KITmutation types between low-risk and very low-risk GISTs(all P>0.05).Patient follow-up was conducted on 87 very low-risk and 210 low-risk GIST pa-tients without other concurrent diseases,with a median follow-up of 86(27-158)months.None of the patients with very low-risk GISTs showed progression;three cases of low-risk GIST had recurrence or metastasis,with progression-free survival(PFS)ranging from 27 to 84 months.The mitotic indices of the primary tumors in these three patients were all 4/5 mm2,which is close to the critical value between the low-and intermediate-risk GIST mitotic indices,and all had KIT exon11 mutations.After the first progression,these three patients were treated with imatinib,and all survived until the end of follow-up,with overall survival ranging from 116 to 155 months.Conclusions:Among patients with low-risk GISTs,a very small number with high mitotic indices may have the potential for recurrence or metastasis,but after re-currence or metastasis,they can still maintain long-term,high-quality survival through targeted therapy,surgery,and other treatment meth-ods.The possibility of postoperative progression in very low-risk patients with GIST is extremely low,and the follow-up interval can be ap-propriately extended to reduce medical costs and alleviate the psychological burden on the patients and their families.

Objective:To investigate the clinical features and genetic variant of a child with West syndrome due to a variant of NEXMIF gene. Methods:A child who was admitted to Department of Pediatrics, the First Medical Center of Chinese PLA General Hospital in March 2021 was selected as the study subject. Clinical data of the patient was collected. The child and his parents were subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing and pathogenicity analysis.Results:The child, a 4-month-old boy, had presented with spastic seizures with no obvious cause. Abnormal EEG, severe hypsarrhythmia, and multiple spastic seizures were discovered. Cranial MRI revealed widening of the extracerebral space at the top of the frontal lobe. Physical examination revealed that he could not hold his head up, and could not respond to sounds or follow objects with eyes. He also has microcephaly, with height < 1 s. The child was diagnosed with West syndrome at a local hospital, and given prednisone orally for 3 months, with seizures under control. Topiramate tablets were taken orally for maintenance treatment, and he has been seizure-free for 7 months. DNA sequencing revealed that he has harbored a de novo nonsense variant of c. 982_c.983delTT (p.L328Dfs*23) in the NEXMIF gene. Conclusion:For children with West syndrome with severe developmental delay or even regression as the first symptoms, uncontrollable seizures and abnormal facial appearance, mutations in the NEXMIF gene should be suspected, and genetic testing can facilitate early diagnosis and treatment.

Objective:To analyze the vaccination recommendations and follow-up for children with special health status.Methods:In this retrospective cohort study, 509 children who attended the Consultation Clinic of Vaccination for Special Health Children in Beijing Children′s Hospital from August 2020 to February 2023 were selected, the children were given vaccination planning advice after the assessment. The clinical data were collected, including the general situation, special health conditions, vaccination recommendations and implementation status, occurrence and outcomes of suspected adverse events following immunization (AEFI) after vaccination. The vaccination situation and safety in these children were evaluated.Results:Among the 509 children, the most common special health conditions were cardiovascular system diseases (103 cases), followed by neurological diseases (88 cases) and neonatal problems (82 cases). After comprehensive evaluation and multidisciplinary collaboration, 399 children (78.4%) were recommended to receive vaccination/catch-up vaccination according to the immunization program, 63 children (12.4%) were recommended to receive some vaccines but temporarily suspend others, and 47 children (9.2%) were recommended to temporarily suspend vaccination. A total of 449 children (88.2%) were actually vaccinated, AEFI occurred in 49 children and 45 cases were considered as general reactions.Conclusions:The majority of children with special health status can be vaccinated, and the overall compliance and safety are high. The individualized immunization evaluation model of multidisciplinary collaboration is conducive to the completion of the immunization program of children with special health status.