Objective To investigate the predictive value of preoperative combined detection of neutrophil-to-lymphocyte ratio (NLR) and prothrombin time-international normalized ratio to albumin ratio (PTAR) for early abdominal infection after liver transplantation. Methods Clinical data of 287 recipients who underwent liver transplantation at the Liver Transplant Center of Beijing Friendship Hospital, Affiliated to Capital Medical University, from January 2020 to April 2024 were retrospectively analyzed. The patients were divided into infection group (n=60) and non-infection group (n=227) based on whether abdominal infection occurred within 30 days after surgery. The distribution characteristics of pathogens and infection time in infected patients were analyzed. Spearman correlation analysis was used to assess the correlation between NLR, PTAR, Child-Pugh score and preoperative model for end-stage liver disease (MELD) score. Univariate and multivariate logistic regression analyses were performed to identify risk factors for abdominal infection. Receiver operating characteristic (ROC) curves were plotted for NLR, PTAR, and the combined prediction model to evaluate their predictive efficacy for abdominal infection after liver transplantation. Based on the cutoff value of the combined model, recipients were divided into low-risk and high-risk groups, and Kaplan-Meier analysis was used to compare the cumulative incidence of abdominal infection within 30 days after surgery between the two groups. Results Among the 287 recipients who underwent liver transplantation, 60 developed bacterial or fungal abdominal infections postoperatively. A total of 86 strains were isolated from infected patients, with Gram-negative bacteria accounting for 58%, Gram-positive bacteria for 36%, and fungi for 5%. Preoperative NLR and PTAR were positively correlated with Child-Pugh and MELD scores (all 1 > r > 0, P < 0.05). Logistic regression analysis showed that preoperative NLR, preoperative PTAR, postoperative ICU stay duration and postoperative biliary leakage were risk factors for abdominal infection within 30 days after surgery. The area under the curve (AUC) for NLR, PTAR, Child-Pugh score and MELD score were 0.771, 0.735, 0.650 and 0.741, respectively. The AUC for the combined NLR and PTAR prediction model was 0.824 (95% confidence interval: 0.763-0.885, P < 0.001), with a cutoff value of 0.168. Kaplan-Meier analysis showed that the cumulative incidence of abdominal infection within 30 days after surgery was lower in the low-risk group than in the high-risk group, with statistically significant difference (P < 0.001). Conclusions Preoperative NLR and PTAR are independent risk factors for abdominal infection within 30 days after liver transplantation. The combined prediction model of NLR and PTAR may effectively identify high-risk recipients for early abdominal infection after liver transplantation, providing basis for early intervention.

Aim To investigate the intracellular up-take and target protein binding characteristics of two Bruton's tyrosine kinase inhibitors(BTKi)with differ-ent selectivities to provide further insights into the mechanisms of drug off-target-related bleeding risk.Methods Ibrutinib(non-selective BTKi)and za-nubrutinib(selective BTKi)were used as study drugs.After incubation of MEC-1 cells and human platelets with drugs,the cellular thermal shift assay(CETSA)was combined with Western blot to obtain the melting curve and isothermal curve to analyze the binding char-acteristics of the two drugs with the target protein BTK.After incubation of MEC-1 cells and human platelets with drugs,the concentrations of the two drugs were detected by liquid chromatography-tandem mass spectrometry(LC-MS/MS)to analyze the intracellular uptake of the two drugs.Results CETSA analysis confirmed that zanubrutinib was more selective for the target protein BTK compared to ibrutinib.LC-MS/MS analysis showed that both drugs were uptaken intracel-lularly by MEC-1 cells and platelets in a concentration-dependent manner.Conclusions While BTKi targe-ting BTK to B lymphocytes exerts therapeutic effects,off-target effects on platelets due to differences in their intracellular uptake,and target-binding characteristics may be one of the reasons for the differences in bleed-ing risk across selective BTKi.

To evaluate the effectiveness and safety of implantable D-shant atrial shunt device in patients with severe pulmonary arterial hypertension(PAH)and right heart failure.A 53-year-old female patient diagnosed with severe idiopathic PAH and right heart failure,her WHO FC grade was Ⅳ.The right heart catheter and implantation of D-shant atrial shunt device were performed under local anesthesia on November 30,2021.A 6 mm×4 cm peripheral artery balloon was selected to dilate the atrial septum and a D-shant atrial shunt device with a fixed 4 mm diameter orifice was implanted into the heart.The clinical symptoms and hemodynamics of the patient was improved after the intervention.Implantation of atrial shunt device as a palliative therapy to established a right to left shunt is another strategy for treating patients with severe PAH in late period,which has good effectiveness and safety.It could be the last replacement therapy to improve symptoms and prolonged lives to drug resistant and severe PAH patients.

The distribution of Ixodes and Ana plasma carried by Ixodes ticks in Anhui Province was clarified as reference for prevention and control of anaplasmosis.In total,630 hard ticks were collected from Jinzhai County,Hanshan County,Jing-de County and Chaohu City in Anhui Province from April to August 2023.Ticks were identified by morphological analysis and 16S rRNA sequencing.Nested PCR with Anaplasma species-specific primers were used to detect 16S rRNA of Anaplasma spe-cies carried by ticks.A phylogenetic tree was constructed using MEGA11.0 software.Of the identified ticks,18.8％(18/96)were Rhipicephalus microplus and 81.2％(78/96)were Haemaphysalis longicorni in Jinzhai County of Anhui Province,all were H.longicorni in Hanshan County and Chaohu City,while the main species in Jingde County was R.microplus.The posi-tive rate of Anaplasma carried by H.longicornis was 30.9％(102/330),which included A.bovis at 1.8％(6/330),A.phagocytophilum at 21.8％(72/330)and uncultured Anaplasma species at 7.3％(24/330).R.microplus was positively cor-related to A.bovis(13.6％,18/132).The uncultured Anaplasma species was mainly detected in host-free ticks.A.phagocy-tophilum was detected in 24.4％of parasitic ticks and 15.8％of host-free ticks.The positive rates of host-free and parasitic ticks were 19.9％and 17.8％,respectively.These results show that H.longicornis and R.microplus were the dominant ticks in several counties of Anhui Province.H.longicornis and R.microplus as well as free and parasitic ticks all carried Anaplas-ma.

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 analyze the high risk factors of obstetric brachial plexus palsy(OBPP),and to explore how to evaluate the relationship between fault medical behavior and OBPP in the process of medical damage forensic identification.Methods A retrospective analysis was carried out on 25 cases of medical damage liability disputes related to OBPP from 2017 to 2021 in Beijing Fayuan Judicial Science Evidence Appraisal Center.The shortcomings of hospitals in birth weight assessment,delivery mode selection,labor process observation and shoulder dystocia management,and the causal relation-ship between them and the damage consequences of the children were summarized.Results Fault medi-cal behavior was assessed as the primary cause in 2 cases,equal cause in 10 cases,secondary cause in 8 cases,minor cause in 1 case,no causal relationship in 1 case,and unclear causal force in 3 cases.Conclusion In the process of forensic identification of OBPP,whether medical behaviors fulfill diagno-sis and treatment obligations should be objectively analyzed from the aspects of prenatal evaluation,de-livery mode notification,standardized use of oxytocin,standard operation of shoulder dystocia,etc.Meanwhile,it is necessary to fully consider the objective risk of different risk factors and the diffi-culty of injury prevention,and comprehensively evaluate the causal force of fault medical behavior in the damage consequences.

ObjectiveTo investigate the effect and mechanism of Taohong Siwutang （TSD） on myocardial ischemia reperfusion injury （MIRI） in ovariectomized （OVX） female mice. MethodAfter the OVX model of female mice was established， the estradiol （E₂） level was detected by enzyme-linked immunosorbent assay （ELISA） to verify the model. Sixty OVX mice were randomly divided into six groups： Sham operation group， model group， low， medium， and high dose groups （9， 18， 36 g·kg^-1） of TSD， and nuclear factor E₂-related factor 2 （Nrf2） inhibitor group， with 10 mice in each group. The MIRI model was verified by a laser speckle flowmeter. The pathological changes in myocardial tissue were detected by 2，3， 5-triphenyltetrazolium chloride （TTC） and hematoxylin-eosin （HE） staining. Serum creatine kinase isoenzyme （CK-MB）， cardiac troponin Ⅰ （CTnⅠ）， malondialdehyde （MDA）， superoxide dismutase （SOD）， interleukin-6 （IL-6）， and interleukin-10 （IL-10） levels were detected by ELISA. The expression of Nrf2 and heme oxygenase-1 （HO-1） were observed by immunofluorescence staining. The expressions of Nrf2， HO-1， apoptotic B-cell lymphomato-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， inflammatory cytokines interleukin-18 （IL-18）， and interleukin-1β （IL-1β） were detected by Western blot. ResultCompared with the sham operation group， the serum levels of CK-MB， CTnⅠ， MDA， and IL-6 in the model group were increased （P<0.01）， and the levels of SOD and IL-10 were decreased （P<0.01）. The damage scores of TTC and HE staining in myocardial tissue were increased （P<0.01）. The expressions of Nrf2 and HO-1 in myocardial tissue by immunofluorescence were decreased （P<0.01）， and the protein expressions of Nrf2， HO-1， and Bcl-2 in myocardial tissue were decreased. The protein expressions of Bax， IL-18， and IL-1β were increased （P<0.01）. Compared with the model group， serum levels of CK-MB， CTnⅠ， MDA， and IL-6 of TSD groups were significantly decreased （P<0.05， P<0.01）， and SOD and IL-10 were significantly increased （P<0.05， P<0.01）. TTC staining and HE staining damage scores of myocardial tissue were significantly decreased （P<0.01）. The expressions of Nrf2 and HO-1 in myocardial tissue by immunofluorescence were increased （P<0.01）. The protein expressions of Nrf2， HO-1， and Bcl-2 were significantly increased （P<0.05， P<0.01）， and those of Bax， IL-18， and IL-1β were significantly decreased （P<0.05， P<0.01）. The effect of the high dose group of TSD was the most significant. The serum levels of CK-MB， CTnⅠ， MDA， and IL-6 in the Nrf2 inhibitor group were significantly increased （P<0.05， P<0.01）， and the levels of SOD and IL-10 were significantly decreased （P<0.05， P<0.01）. The damage scores of TTC and HE staining in myocardial tissue were significantly increased （P<0.01）. The expressions of Nrf2 and HO-1 in myocardial tissue by immunofluorescence were significantly decreased （P<0.01）. The protein expressions of Nrf2， HO-1， and Bcl-2 in myocardial tissue were significantly decreased， and those of Bax， IL-18， and IL-1β were significantly increased （P<0.01）. ConclusionTSD can alleviate MIRI in OVX mice， reduce oxidative stress response and the release of inflammatory factors， and inhibit apoptosis， playing a protective role in OVX mice with MIRI， which may be related to the activation of Nrf2/HO-1 signaling pathway.

Atherosclerosis caused by disorders of lipid metabolism is the main pathological basis of atherosclerotic cardiovascular disease.Statins are the cornerstone of lipid-modulating therapy for this type of disease,but in practice there are still some patients with suboptimal lipid management.Proprotein convertase subtilisin/kexin type 9(PCSK9)inhibitors have been gradually applied as a new class of lipid-modulating drugs for the treatment in patients with this type of disease,and recent studies have shown that in addition to regulating lipid metabolism,PCSK9 inhibitors also have potential anti-inflammatory and anti-platelet activation effects.This article sorts out the multiple pharmacological mechanisms of action of PCSK9 inhibitors and the current status of clinical research of PCSK9 inhibitors.Besides,it discusses the factors that may affect the efficacy of PCSK9 inhibitors,in order to provide a reference for the safe and rational medication of PCSK9 inhibitors.

italic>Acanthopanax senticosus is one of the genuine regional herb in Northeast China. In this study, we identified the germplasm resources of commercial A. senticosus samples based on atpI and atpB_rbcL according to the previous chloroplast genome sequencing results, and determinated the content of syringin by HPLC to evaluated the quality of commercial samples. A total of 80 A. senticosus samples were collected from 47 cities in 24 provinces. DNA was extracted to amplify the products of atpI and atpB_rbcL by PCR. The results showed that 7 haplotypes (H2, H5, H8, H10, H12, H14, H23) were formed by the combined analysis of the two gene fragments. H2 from Yichun in Heilongjiang, Shangzhi in Harbin, Suihua in Heilongjiang, Fushun in Liaoning, Benxi in Liaoning, Changbai in Jilin and Jingyu in Jilin were the dominant genotype, representing 58.75% of the total samples. H14 and H23 were the unique haplotypes of the producing area. It is speculated that the commercial A. senticosus samples with haplotypes of H14 and H23 are from Raohe, Shuangyashan, Heilongjiang and Mingshui, Suihua, Heilongjiang, respectively. HPLC analysis indicated that the content of syringin in 73.96% of the samples met the Pharmacopoeia standards. There was a significant difference in the content of syringin among the samples, ranging from 0.003 7% to 0.524 5%, with a difference of 0.520 8%, indicating that the quality of the samples in the market of A. senticosus was uneven. However, there were no significant differences in the contents of syringin in the commercial A. senticosus among different haplotypes. The content of syringin in the haplotype H23 in the market sample is relatively high, so it may be a germplasm with better quality. This study researched the germplasm resources and medicinal materials quality of commercial A. senticosus samples and will help guide the commercial circulation, reasonable medication of A. senticosus, and the screening of excellent germplasm.

Bacterial biofilms gave rise to persistent infections and multi-organ failure, thereby posing a serious threat to human health. Biofilms were formed by cross-linking of hydrophobic extracellular polymeric substances (EPS), such as proteins, polysaccharides, and eDNA, which were synthesized by bacteria themselves after adhesion and colonization on biological surfaces. They had the characteristics of dense structure, high adhesiveness and low drug permeability, and had been found in many human organs or tissues, such as the brain, heart, liver, spleen, lungs, kidneys, gastrointestinal tract, and skeleton. By releasing pro-inflammatory bacterial metabolites including endotoxins, exotoxins and interleukin, biofilms stimulated the body’s immune system to secrete inflammatory factors. These factors triggered local inflammation and chronic infections. Those were the key reason for the failure of traditional clinical drug therapy for infectious diseases.In order to cope with the increasingly severe drug-resistant infections, it was urgent to develop new therapeutic strategies for bacterial-biofilm eradication and anti-bacterial infections. Based on the nanoscale structure and biocompatible activity, nanobiomaterials had the advantages of specific targeting, intelligent delivery, high drug loading and low toxicity, which could realize efficient intervention and precise treatment of drug-resistant bacterial biofilms. This paper highlighted multiple strategies of biofilms eradication based on nanobiomaterials. For example, nanobiomaterials combined with EPS degrading enzymes could be used for targeted hydrolysis of bacterial biofilms, and effectively increased the drug enrichment within biofilms. By loading quorum sensing inhibitors, nanotechnology was also an effective strategy for eradicating bacterial biofilms and recovering the infectious symptoms. Nanobiomaterials could intervene the bacterial metabolism and break the bacterial survival homeostasis by blocking the uptake of nutrients. Moreover, energy-driven micro-nano robotics had shown excellent performance in active delivery and biofilm eradication. Micro-nano robots could penetrate physiological barriers by exogenous or endogenous driving modes such as by biological or chemical methods, ultrasound, and magnetic field, and deliver drugs to the infection sites accurately. Achieving this using conventional drugs was difficult. Overall, the paper described the biological properties and drug-resistant molecular mechanisms of bacterial biofilms, and highlighted therapeutic strategies from different perspectives by nanobiomaterials, such as dispersing bacterial mature biofilms, blocking quorum sensing, inhibiting bacterial metabolism, and energy driving penetration. In addition, we presented the key challenges still faced by nanobiomaterials in combating bacterial biofilm infections. Firstly, the dense structure of EPS caused biofilms spatial heterogeneity and metabolic heterogeneity, which created exacting requirements for the design, construction and preparation process of nanobiomaterials. Secondly, biofilm disruption carried the risk of spread and infection the pathogenic bacteria, which might lead to other infections. Finally, we emphasized the role of nanobiomaterials in the development trends and translational prospects in biofilm treatment.