Obesity and its related metabolic diseases have become a major global public health threat, and its rising incidence significantly increases the risk of cardiovascular and cerebrovascular diseases, diabetes and other complications. Pancreatic lipase is a key enzyme that converts food-borne lipids into triglycerides and fatty acids, and the effective inhibition of its activity has become an important strategy for the treatment of obesity. This paper discusses the screening methods of pancreatic lipase inhibitors, and summarizes and reviews the basic principles, advantages and disadvantages and application status of traditional screening methods, modern new screening methods and virtual screening methods. In view of the problems faced by the screening methods of pancreatic lipase inhibitors, future research urgently needs to move towards a collaborative innovation path of multi-technology integration, intelligent screening and complex systematization of traditional Chinese medicine, so as to open up new research paradigms.

Stroke is the leading cause of death and disability among adults in China， and its common complications include digestive system abnormalities， cognitive impairment， depression， stroke-associated pneumonia， and hemiplegia. The combination of traditional Chinese and Western medicine has great potential in treating post-stroke complications. Xinglou Chengqitang （XLCQT） is a representative prescription of alleviating the disease in the upper part by treating the lower part. It has definite therapeutic effect and high safety. Clinically， XLCQT is often used to treat stroke and its complications. However， the quantity and quality of clinical trials of XLCQT in treating post-stroke complications need to be improved. Additionally， since the basic research is weak， the material basis and multi-target mechanism for the efficacy of this prescription are unknown. This article reviews XLCQT in terms of the pharmacodynamic basis， medicinal properties， safety evaluation， and progress in clinical research and mechanisms in treating post-stroke complications. This article summarizes 22 key active ingredients of XLCQT in treating acute stroke complicated with syndrome of phlegm heat and fu-organ excess. Among these key active ingredients， resveratrol， kaempferol， luteolin， chrysoeriol， apigenin， （+）-catechin， and adenosine have good pharmacokinetic properties and high bioavailability. The mechanisms of XLCQT in treating post-stroke complications are complex， including inflammatory response， brain-gut axis， hypothalamic-pituitary-adrenal （HPA） axis， intestinal flora， neurotrophic factors， autophagy， oxidative stress， and free radical damage. This review helps to deeply understand the pharmacodynamic basis and mechanisms of XLCQT in treating post-stroke complications and provides a theoretical basis for the clinical application of XLCQT against post-stroke complications and the development of drugs.

Objective: To construct gene recombinant expression plasmids of human anti-P antibody with IgG1 and kappa chain based on the human hybridoma cell line. Methods: Starting from the specific RT-PCR products encoding the variable regions of the IgH chain and IgL chain of the anti-P monoclonal cell line, appropriate restriction enzyme digestion sites were introduced at both ends of the VH and VL fragments through nested PCR. The plasmids carrying the antibody constant region and the nested PCR products of VH and VL were ligated by the action of T4 ligase and subsequently transferred into competent E. coli DH5ɑ, and positive clones were selected in the antibiotic resistant LB medium. After sequence confirmation, recombinant plasmids DNA were transfected into HEK293T cells, and the recombinant antibody obtained in the culture supernatant. The characteristics of recombinant expression antibodies were determined by using rapid antibody isotying kit, serological agglutination tests and flow cytometry. Results: Recombinant gene expression vectors, pFUSEss-CHIg-hG1+VH, pFUSE2ss-CLIg-hκ+VL, were successfully constructed. Human IgG1 kappa light chain antibodies were detected in the supernatant of HEK293T cells transient transfected with recombinant plasmids. After the supernatant was ultra-filtered and concentrated, it could cause agglutination reactions with P antigen-positive red blood cells. The mean fluorescence intensity (MFI) of the reaction between recombinant antibodies and antigen-positive red blood cells in flow cytometry experiments was higher than that of antigen-negative red blood cells. Conclusion: The experimental study on the conversion of red blood group antibody types by genetic engineering technology represents a beneficial exploration towards establishing a feasible technical route for the development of genetic recombination and modification of antibodies reagent.

Pegylated interferon α-2b （PEG-IFN-α-2b） is currently a first-line drug for the treatment of chronic hepatitis B virus infection and is widely used in clinical practice. This drug has multiple effects of inhibiting viral replication， regulating immunity， and improving liver function， and some patients can achieve clinical cure. However， it often causes various adverse reactions during treatment， which are important factors for compromising treatment compliance and efficacy. This article systematically reviews the adverse reactions and their mechanisms during PEG-IFN-α-2b therapy for chronic hepatitis B， including influenza-like symptoms， peripheral blood cytopenia， thyroid dysfunction， and neuropsychiatric symptoms， and it also summarizes the monitoring and management strategies for these adverse reactions， in order to provide evidence-based guidance for clinical decision-making and emphasize the importance of individualized treatment.

Objective:To analyze the carriage status, subtype distribution and flanking gene sequence characteristics of oxacillinases (OXA enzyme) in 241 clinical strains of Pseudomonas aeruginosa, and assess their roles in the drug resistance of Pseudomonas aeruginosa and ability to horizontally transfer across species. Methods:Clinical P. aeruginosa isolates were collected from four hospitals in Sanya, Tangshan, Zhangjiakou, and Beijing. The prevalence of oxacillinases and their flanking gene sequences was analyzed by whole-genome sequencing (NGS) and bioinformatic approaches. Results:A total of 241 isolates of P. aeruginosa were gathered, and 35 blaOXA subtypes were identified through screening of 252 blaOXA genes. These genes were classified into three subfamilies: blaOXA-50-like (241, 95.6%), blaOXA-1-like (9, 3.6%) and blaOXA-10-like (2, 0.8%). Among these, 11 subtypes (11, 31.4%) were novel blaOXA subtypes. Nine of these belonged to the blaOXA-50-like subfamily and were designated as blaOXA-1244, blaOXA-1245, blaOXA-1246, blaOXA-1250, blaOXA-1252, blaOXA-1253, blaOXA-1254, blaOXA-1255, and blaOXA-1256. The remaining two belonged to the blaOXA-10-like subfamily and were named blaOXA-1247 and blaOXA-1248. Compared to the amino acid sequence of OXA-10, the newly identified subtype OXA-1247 exhibited a mutation at position 117, where a valine was replaced by a leucine. This change was thought to improve the enzyme′s ability to hydrolyze carbapenems. In the analysis of the flanking sequences of the blaOXA genes, Class I integrons were identified in four bacterial strains. The variable regions of these integrons carried three distinct patterns of resistance gene cassettes: aac( 6′) -Ib-blaOXA-1247-ant( 3′′) -Ia, aac( 6′) -Ib-blaOXA-1248 and aac( 6′) -Ib- blaIMP-45-blaOXA-1-catB3. Among these, the strain BJ2326 carried a class I integron that was connected to the downstream IS CR1 element to form a composite class I integron structure, additionally carrying the resistance gene blaPER-1. Out of the 223 non-wild-type P. aeruginosa strains, 127 strains exhibited non-wild-type profiles to the four beta-lactam antibiotics MEM, CAZ, FEP, and TZP, with the combination of MEM+CAZ+FEP being the most prevalent, representing 57.0% of the total. Conclusions:The blaOXA genes in 241 clinical P. aeruginosa strains showed diversity. Some blaOXA genes had a co-transfer risk with the metallo-β-lactamase resistance gene blaIMP-45. Among the 11 newly discovered blaOXA subtypes, the new subtype OXA-1247 may have carbapenemase activity and potential for horizontal transfer.

Objective:To construct a performance management model based on comprehensive evaluation method with probability weight,and to explore its application value in management for emergency equipment.Methods:A performance evaluation system was formulated by performance management model from three dimensions included operation quality,cost investment and social benefit of emergency equipment.Probability weight method was used to assign the index weight,and management countermeasures included engineering technical support,expenditure control and improvement of social benefit were formulated according to the comprehensive evaluation results.A total of 109 emergency equipment in clinical use at Renji Hospital,Shanghai Jiao Tong University School of Medicine from March 2022 to February 2024 were selected.The management method with conventional evaluation model(conventional evaluation management method)was adopted to manage 103 equipment during March 2022 and February 2023,and the management method with performance management model based on comprehensive evaluation method with probability weight(comprehensive evaluation management method)was adopted to manage 104 equipment(included the used 98 equipment that were managed by conventional evaluation management method at the first stage,and 6 new equipment)during March 2023 and February 2024.The operation quality and management cost of the two kinds of management methods for equipment were compared.A self-made questionnaire survey was conducted to investigate the performance evaluation of operators,who used equipment,for the two kinds of management methods in using equipment.Results:The average use rate,data integrity rate and pass rate of quality inspection of clinical emergency equipment of adopting the comprehensive evaluation management method were respectively(96.61±1.52)%,(97.74±1.91)%and(95.96±1.19)%,all of which were higher than those of adopting conventional evaluation management method.The average values of the alarm rate and the damage rate of the component and accessories of the system were respectively(1.24±0.83)%and(1.08±0.56)%,both of which were lower than those of the conventional evaluation management method.The differences of the above indicators were statistically significant(t=3.410,3.292,3.848,2.967,2.825,P<0.05).The average amplification of the management investment of respiratory therapy,diagnosis and treatment of electrocardiogram,rescue treatment,basic treatment and other management investment of emergency equipment were lower than those of the conventional evaluation management method,and the differences were statistically significant(t=3.533,3.487,4.002,3.317,2.726,P<0.05).The scores of operators who used equipment for configurations quantity,configuration quality and management level that adopted comprehensive evaluation management method were all higher than those that adopted conventional evaluation management method,and the differences were statistically significant(t=3.183,3.934,2.363,P<0.05).Conclusion:The performance management model based on the comprehensive evaluation method with probability weight can enhance the operational quality of clinical emergency equipment,and control the management cost of equipment,and improve the service level of equipment.

Objective To retrospectively analyze the clinical efficacy of Xiazhu Sanjie Prescription in treating pulmonary nodules.Methods A retrospective study was conducted on 58 patients of pulmonary nodules with spleen deficiency and excessive dampness syndrome who received Xiazhu Sanjie Prescription for 3 months or more at Dongzhimen Hospital,Beijing University of Chinese Medicine,from January 2021 to September 2024 were set as the observation group.Another 58 patients of pulmonary nodules with spleen deficiency excessive dampness syndrome who did not receive TCM intervention during the same period were selected as the control group.Basic information,TCM syndromes,and the diameters of pulmonary nodules on chest HRCT at the first and last visit were collected.Changes in nodule diameter,TCM syndrome scores,and TCM syndrome efficacy were compared between the two groups.Results Compared with the control group,the nodule diameter in the observation group significantly decreased(P<0.05),and the proportion of nodule disappearance or reduction was significantly higher than the control group(P<0.05).The TCM syndrome scores for symptoms such as excessive phlegm,fatigue,loss of appetite,pale complexion,irregular bowel movements,chest tightness,shortness of breath,heaviness of the head and limbs,and abdominal distention showed significant improvement in the observation group both compared to pre-treatment and the control group(P<0.05).The total effective rate of TCM syndromes in the observation group was 93.10%(54/58),while the control group was 17.24%(10/58).The observation group was significantly better than the control group(P<0.05).Conclusion Xiazhu Sanjie Prescription can reduce the diameter of pulmonary nodules to some extent and improve TCM syndromes in patients with pulmonary nodules.

Objective:To explore the relationship between the differential genes derived from transcriptome mRNA sequencing and prognosis among heart failure patients with mildly reduced ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF).Methods:This was a case-control study. Ten patients with HFmrEF and 10 patients with HFpEF treated at TEDA International Cardiovascular Disease Hospital from November 2021 to January 2022 were selected and differentially expressed genes were screened by transcriptome mRNA sequencing. Ten healthy people served as control group. In addition, 50 patients with HFmrEF, 62 patients with HFpEF, who were treated at TEDA International Cardiovascular Disease Hospital at the same period, were selected as validation groups, 57 healthy people served as control validation group. Real-time quantitative PCR (RT-qPCR) was used to detect the expression of differential genes in each group. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used to assess the differential diagnosis and prognostic value of differential genes in these patients. Patients were followed up regularly to document adverse events within 1 year after discharge including cardiac death and readmission for heart failure. Survival analysis was performed using Kaplan-Meier curves and tested by log rank test. Cox regression analysis was used to explore whether differential mRNA was risk factors for poor prognosis in HFmrEF and HFpEF patients.Results:A total of four genes were differentially expressed (three upregulated and one downregulated gene) between the HFmrEF group and HFpEF group (adjust P<0.05). SLC12A1, C15orf48 and SPP1 were associated with the progress of cardiovascular disease, and selected for validation in the clinical cohort. RT-qPCR results showed that the gene expression of SLC12A1 in the HFmrEF group was significantly higher than that in the HFpEF group ( P<0.001). The AUC for the adjunctive differential diagnostic value of SLC12A1 for HFmrEF and HFpEF was 0.802 ( P<0.001) and the AUC of SLC12A1 with a cut-off value of 6.634 was 0.737 ( P=0.003) in determining poor prognosis in patients with HFpEF. Kaplan-Meier survival analysis showed that patients with SLC12A1≤6.634 had a higher incidence of adverse cardiac events than patients with SLC12A1 >6.634 ( P=0.001). Cox regression analysis showed that the risk of adverse cardiac events in the SLC12A1 ≤6.634 group was 6.787 times higher than in the SLC12A1 >6.634 group ( HR=6.787, P=0.011). Conclusions:Transcriptome mRNA sequencing analysis is valuable for detecting clinical relevant differentially expressed genes in HFmrEF and HFpEF patients, among which SLC12A1 can be used as a novel molecular biomarker to aid the differential diagnosis of HFmrEF and HFpEF. In addition, SLC12A1 may be used as an adjunctive biomarker for the prognosis evaluation in patients with HFpEF.

Objective To analyze the differences in cerebral blood flow(CBF)characteristics among children with different subtypes of attention deficit and hyperactivity disorder(ADHD)and their relationship with executive function using arterial spin labeling(ASL)technology.Methods A case-control study was conducted,including children diagnosed with ADHD at the outpatient clinic of Peking University Sixth Hospital from July 2015 to December 2019 as the ADHD group,and typically developing schoolchildren from January to December 2021 as the healthy control group.Both groups underwent pseudo-continuous ASL(pCASL)scanning to measure CBF,and executive function was assessed using the parent version of the Behavior Rating Inventory of Executive Function(BRIEF).Differences in CBF between ADHD children and healthy controls were com-pared.For brain regions showing significant group differences,CBF values were extracted and linear regression models were constructed with BRIEF scores to further explore the relationship between regional CBF and execu-tive function.Results A total of 134 boys with ADHD were included[83 with ADHD predominantly inat-tentive subtype(ADHD-Ⅰ)and 51 with ADHD combined subtype(ADHD-C)],along with 25 healthy control boys.Intergroup comparisons revealed that the CBF in the left middle temporal gyrus was significantly lower in ADHD-C children compared to both ADHD-Ⅰ children(P=0.010)and healthy controls(P＜0.001),while no significant difference was observed between ADHD-Ⅰ children and healthy controls(P=0.280).After adjusting for age and total IQ scores,the linear regression model showed that the CBF in the left middle temporal gyrus of ADHD-C children was negatively correlated with the planning/organization score on the BRIEF(β=-0.062,P=0.030).Conclusions The CBF in the left middle temporal gyrus of boys with ADHD-C is significantly lower than that of boys with ADHD-Ⅰ and healthy controls.This reduced regional CBF may be associated with executive function deficits in organization and planning abilities in ADHD-C,providing new insights into the neurobiological mechanisms underlying ADHD subtypes.

The small-molecule alkaloid halofuginone(HF)is obtained from febrifugine.Recent studies on HF have aroused widespread attention owing to its universal range of noteworthy biological activities and therapeutic functions,which range from parasite infections and fibrosis to autoimmune diseases.In particular,HF is believed to play an excellent anticancer role by suppressing the proliferation,adhesion,metastasis,and invasion of cancers.This review supports the goal of demonstrating various anticancer effects and molecular mechanisms of HF.In the studies covered in this review,the anticancer molecular mechanisms of HF mainly included transforming growth factor-β(TGF-β)/Smad-3/nuclear factor erythroid 2-related factor 2(Nrf2),serine/threonine kinase proteins(Akt)/mechanistic target of rapa-mycin complex 1(mTORC1)/wingless/integrated(Wnt)/β-catenin,the exosomal microRNA-31(miR-31)/histone deacetylase 2(HDAC2)signaling pathway,and the interaction of the extracellular matrix(ECM)and immune cells.Notably,HF,as a novel type of adenosine triphosphate(ATP)-dependent inhibitor that is often combined with prolyl transfer RNA synthetase(ProRS)and amino acid starvation therapy(AAS)to suppress the formation of ribosome,further exerts a significant effect on the tumor microenvironment(TME).Additionally,the combination of HF with other drugs or therapies obtained universal attention.Our results showed that HF has significant potential for clinical cancer treatment.