The coronavirus disease 2019 (COVID-19) is an acute infectious disease caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which has led to serious worldwide economic burden. Due to the continuous emergence of variants, vaccines and monoclonal antibodies are only partial effective against infections caused by distinct strains of SARS-CoV-2. Therefore, it is still of great importance to call for the development of broad-spectrum and effective small molecule drugs to combat both current and future outbreaks triggered by SARS-CoV-2. Cathepsin L (CatL) cleaves the spike glycoprotein (S) of SARS-CoV-2, playing an indispensable role in enhancing virus entry into host cells. Therefore CatL is one of the ideal targets for the development of pan-coronavirus inhibitor-based drugs. In this study, a CatL enzyme inhibitor screening model was established based on fluorescein labeled substrate. Two CatL inhibitors IMB 6290 and IMB 8014 with low cytotoxicity were obtained through high-throughput screening, the half inhibition concentrations (IC₅₀) of which were 11.53 ± 0.68 and 1.56 ± 1.10 μmol·L^-1, respectively. SDS-PAGE and cell-cell fusion experiments confirmed that the compounds inhibited the hydrolysis of S protein by CatL in a concentration-dependent manner. Surface plasmon resonance (SPR) detection showed that both compounds exhibited moderate binding affinity with CatL. Molecular docking revealed the binding mode between the compound and the CatL active pocket. The pseudovirus experiment further confirmed the inhibitory effects of IMB 8014 on the S protein mediated entry process. In vitro pharmacokinetic evaluation indicated that the compounds had relatively good drug-likeness properties. Our research suggested that these two compounds have the potential to be further developed as antiviral drugs for COVID-19 treatment.

Objective To investigate the toxicokinetic differences of 3,4-methylenedioxy-N-methylamphetamine(MDMA)and its metabolite 4,5-methylene dioxy amphetamine(MDA)in rats af-ter single and continuous administration of MDMA,providing reference data for the forensic identifica-tion of MDMA.Methods A total of 24 rats in the single administration group were randomly divided into 5,10 and 20 mg/kg experimental groups and the control group,with 6 rats in each group.The ex-perimental group was given intraperitoneal injection of MDMA,and the control group was given intraperi-toneal injection of the same volume of normal saline as the experimental group.The amount of 0.5 mL blood was collected from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.In the continuous administration group,24 rats were randomly divided into the experi-mental group(18 rats)and the control group(6 rats).The experimental group was given MDMA 7 d by continuous intraperitoneal injection in increments of 5,7,9,11,13,15,17 mg/kg per day,respectively,while the control group was given the same volume of normal saline as the experimental group by in-traperitoneal injection.On the eighth day,the experimental rats were randomly divided into 5,10 and 20 mg/kg dose groups,with 6 rats in each group.MDMA was injected intraperitoneally,and the con-trol group was injected intraperitoneally with the same volume of normal saline as the experimental group.On the eighth day,0.5 mL of blood was taken from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.Liquid chromatography-triple quadrupole tandem mass spectrometry was used to detect MDMA and MDA levels,and statistical software was employed for data analysis.Results In the single-administration group,peak concentrations of MDMA and MDA were reached at 5 min and 1 h after administration,respectively,with the largest detection time limit of 12 h.In the continuous administration group,peak concentrations were reached at 30 min and 1.5 h af-ter administration,respectively,with the largest detection time limit of 10 h.Nonlinear fitting equations for the concentration ratio of MDMA and MDA in plasma and administration time in the single-administration group and continuous administration group were as follows:T=10.362C-1.183,R2=0.974 6;T=7.397 3C-0.694,R2=0.961 5(T:injection time;C:concentration ratio of MDMA to MDA in plasma).Conclusions The toxicokinetic data of MDMA and its metabolite MDA in rats,obtained through single and continuous administration,including peak concentration,peak time,detection time limit,and the relationship between concentration ratio and administration time,provide a theoretical and data foundation for relevant forensic identification.

The growth of three plague phages from Qinghai Plateau in two Yersinia pestis strains(plague vaccine strains EV76 and 614F)and four non-Yersinia pestis strains(Yersinia pseudotuberculosis PTB3,PTB5,Escherichia coli V517,and Yersinia enterocolitica 52302-2)were detected through a micromethod based on the OmniLogTM microbial identification system and by the drop method,to provide a scientific basis for future ecological studies and classification based on the host range.For plague vaccine strains EV76 and 614F,successful phage infection and subsequent phage growth were observed in the host bacte-rium.Diminished bacterial growth and respiration and a concomitant decrease in color were observed with the OmniLogTM mi-crobial identification system at 33 ℃ for 48 h.Yersinia pseudotuberculosis PTB5 was sensitive to Yersinia pestis phage 476,but Yersinia pseudotuberculosis PST5 was insensitive to phage 087 and 072204.Three strains of non-Yersinia pestis(Yersinia pseudotuberculosis PTB3,Escherichia coli V517,and Yersinia enterocolitica 52302-2)were insensitive to Yersinia pestis pha-ges 087,072204,and 476 showed similar growth curves.The growth of phages 476 and 087,as determined with the drop method,in two Yersinia pestis strains(plague vaccine strains EV76 and 614F)and four non-Yersinia pestis strains(Yersinia pseudotuberculosis PTB3,Escherichia coli V517,and Yersin-ia enterocolitica 52302-2)showed the same results at 37 ℃,on the basis of comparisons with the OmniLogTM microbial i-dentification system;in contrast,phages 072204 did not show plaques on solid medium at 37 ℃ with plague vaccine strains EV76 and 614F.Determination based on the OmniLogTM detection system can be used as an alternative to the traditional determination of the host range,thus providing favorable application val-ue for determining the interaction between the phage and host bacteria.

Based on the theory of the uterus is an extraordinary fu （腑） organ， it is believed that the core pathogenesis of precocious puberty in girls is the dysfunction of the uterus in storing and draining， while the basis of the disease is the delicate and vulnerable zang fu （脏腑） organs； the imbalance of qi and blood in the Chong and Ren mai （冲任） is the key link of the pathogenesis， and five zang （脏） organs dysharmony is responsible for the prolongation of the disease. For treatment， it is advocated to conform to the physiological characteristics that zang fu organs are delicate and fragile in girls， focus on regulating the uterus， and take into account the harmonization of the zang fu organs； the method of consolidating and nourishing yin is suggested as the basic treatment method， and self-made Xingzaoshu Formula （性早熟方） is commonly used. Considering that the uterus of girls is delicate and vulnerable， neutral medicinals are mainly used， and drastic supplementation and strong attack are avoided； pulse administration of Chinese herbal medicine is advocated. Since the condition of precocious puberty is often prolonged， Chinese herbal medicine together with medicinal diet is often used in the later stage of treatment to harmonize the zang fu organs， and self-made medicinal diet Xingzaoshu Soup （性早熟煲） is often used.

Lipopolysaccharides (LPS) are major outer membrane components of Gram-negative bacteria. Unlike most Gram-negative bacteria, Acinetobacter baumannii can still survive and acquire polymyxin resistance after complete loss of LPS. Previous studies of LPS-deficient Acinetobacter baumannii mostly focused on LPS-deficient strains induced by polymyxin, whose background was complex and unstable. To investigate LPS loss-mediated polymyxin resistant-Acinetobacter baumannii, this study constructed a stable and clear background LPS-deficient strain by knocking out lpxC gene in Acinetobacter baumannii ATCC 19606 with CIRSPR/Cas9, and then studied the phenotypic changes of the lpxC-deficient strain including morphology, growth rate, antibiotic susceptibility, virulence, membrane permeability, and membrane potential. Animal experiments were approved by the Animal Care and Welfare Committee Institute of Medicinal Biotechnology, CAMS and PUMC (approval number: IMB-20240119D₉). The results indicated that the lpxC gene of Acinetobacter baumannii ATCC 19606 was successfully knocked out. After losing the lpxC, the strain underwent the morphological change from rod-shaped to spherical. Furthermore, it leads to reduced growth rate, enhanced membrane permeability, decreased membrane potential, lower virulence, and increased antibiotic susceptibility to β-lactams, quinolones, aminoglycosides, macrolides, glycopeptides. The lpxC deletion results in significant changes in membrane homeostasis and adaptability of Acinetobacter baumannii. Understanding the phenotypic changes of colistin-resistant Acinetobacter baumannii mediated by LPS loss is useful for exploring the resistance mechanism of Acinetobacter baumannii and developing new therapeutic strategies.

Eleven compounds were isolated from Eucommia ulmoides by silica gel, Sephadex LH-20, HW-40C column chromatography and semi-preparative HPLC. Their structures were identified by modern spectroscopic methods as neoeucommiate A (1), (7S,8R)-dihydrodehydrodiconiferyl alcohol (2), urolignoside (3), ficusal (4), tiruneesiin (5), glochidioboside (6), forsythialansides B (7), ecdysanol B (8), (+)-syringaresinol-4-O-β-D-glucopyranoside (9), (+)-pinoresinol 4-O-[6ʹʹ-O-vanilloyl]-β-D-glucopyranoside (10), samsesquinoside (11). Compound 1 is a new compound, compounds 3-7, 10 and 11 were isolated from Eucommia ulmoides for the first time.

Objective To investigate the current status,obstacles,and specific needs associated with the application of transradial access(TRA)in peripheral interventions in Chinese hospitals,with the aim of promoting the broader adoption of TRA in interventional procedures.Methods The Committee of Interventional Oncology of China Anti-Cancer Association conducted a cross-sectional questionnaire survey to investigate and analyze the nationwide situation of TRA in peripheral interventional surgeries in 2022.Results Personnel from 60 hospitals participated in the questionnaire.The results showed that the number of peripheral interventionals performed using TRA was significantly lower than that performed using transfemoral access(TFA),with considerable variability among hospitals.The primary obstacles to the adoption of TRA were the lack of suitable catheters and the difficulty of radial artery puncture.Approximately 86.67％of the institutions expressed a high expectation for the innovation of new TRA-specific devices,particularly catheters,microcatheters,and guidewires.60.00％of medical institutions indicated a strong desire for systematic training and participation in multi-center clinical trials.Conclusions TRA peripheral intervention is feasible in many hospitals in China,however,systematic training and further promotion of TRA are essential.The innovation of new TRA-specific devices and TRA in peripheral intervention is urgent.

Purpose::Cerebral edema (CE) is the main secondary injury following traumatic brain injury (TBI) caused by road traffic accidents (RTAs). It is challenging to be predicted timely. In this study, we aimed to develop a prediction model for CE by identifying its risk factors and comparing the timing of edema occurrence in TBI patients with varying levels of injuries.Methods::This case-control study included 218 patients with TBI caused by RTAs. The cohort was divided into CE and non-CE groups, according to CT results within 7 days. Demographic data, imaging data, and clinical data were collected and analyzed. Quantitative variables that follow normal distribution were presented as mean ± standard deviation, those that do not follow normal distribution were presented as median (Q 1, Q 3). Categorical variables were expressed as percentages. The Chi-square test and logistic regression analysis were used to identify risk factors for CE. Logistic curve fitting was performed to predict the time to secondary CE in TBI patients with different levels of injuries. The efficacy of the model was evaluated using the receiver operator characteristic curve. Results::According to the study, almost half (47.3%) of the patients were found to have CE. The risk factors associated with CE were bilateral frontal lobe contusion, unilateral frontal lobe contusion, cerebral contusion, subarachnoid hemorrhage, and abbreviated injury scale (AIS). The odds ratio values for these factors were 7.27 (95% confidence interval ( CI): 2.08 -25.42, p = 0.002), 2.85 (95% CI: 1.11 -7.31, p = 0.030), 2.62 (95% CI: 1.12 -6.13, p = 0.027), 2.44 (95% CI: 1.25 -4.76, p = 0.009), and 1.5 (95% CI: 1.10 -2.04, p = 0.009), respectively. We also observed that patients with mild/moderate TBI (AIS ≤ 3) had a 50% probability of developing CE 19.7 h after injury (χ 2= 13.82, adjusted R2 = 0.51), while patients with severe TBI (AIS > 3) developed CE after 12.5 h (χ 2= 18.48, adjusted R2 = 0.54). Finally, we conducted a receiver operator characteristic curve analysis of CE time, which showed an area under the curve of 0.744 and 0.672 for severe and mild/moderate TBI, respectively. Conclusion::Our study found that the onset of CE in individuals with TBI resulting from RTAs was correlated with the severity of the injury. Specifically, those with more severe injuries experienced an earlier onset of CE. These findings suggest that there is a critical time window for clinical intervention in cases of CE secondary to TBI.

Objective To study the clinical and pathological characteristics,as well as diagnosis,treatment methods and prognosis of adult patients with chronic active Epstein-Barr virus infection(CAEBVI).Methods Clinical and pathological data of 8 adult patients with CAEBVI admitted to a hospital in Gansu Province from January 2017 to December 2022 were collected retrospectively,clinical and histopathological characteristics,EBV-related test re-sults,as well as treatment and prognosis of patients were analyzed.Results Among 8 CAEBVI patients,3 were males and 5 were females,with the median age of 21.5 years.The median time from onset to diagnosis of CAEBVI was 7 months.The main manifestations were fever,pancytopenia(involving two or three peripheral blood lines),as well as lymph node enlargement,hepatomegaly and splenomegaly.The quantifications of plasma EBV nucleic acid(DNA)were all＞1.0 × 103.The sorting results of EBV infected cells showed that 3 cases were T lymphocytes in-fection,2 were NK cell infection,and 3 were co-infection of T lymphocytes and NK cells.Bone marrow cytological examination of 8 patients showed no atypical lymphocytes,while 6 patients showed hemophagocytic cells.Flow cy-tometey(FCM)typing results showed that no abnormal cell population was detected in all the 8 patients,and no myeloid,B lymphocyte,T lymphocyte and NK cell markers were expressed.The positive rate of T cell receptor(TCR)gene rearrangement was 37.5％(n=3).Histopathology showed that most cases(n=6,75.0％)expressed CD3,partial cases expressed CD4,CD8,CD56,TIA-1,and EBV encoded RNA(EBER),all were positive.The survival rate of patients after treatment was 50.0％(n=4),the follow-up time was 6-51 months,the 1-year sur-vival rate was 85.7％,and the median survival time was 24 months.Conclusion CAEBVI is characterized by varia-ble clinical manifestations that may lead to fatal complications.Early diagnosis and individualized treatment should be performed to reduce mortality of patients.

Objective:To investigate the clinical characteristics and prognosis of primary bone marrow lymphoma.Methods:The clinical data of 6 patients with primary bone marrow lymphoma admitted to Gansu Provincial People's Hospital from February 2011 to March 2023 were collected,and their clinical characteristics and prognosis were retrospectively analyzed and summarized.Results:The median age of 6 patients was 61(52-74)years old.There were 2 males and 4 females.All patients had fever and abnormal blood routine examination.Physical examination and imaging examination showed no lymphadenopathy,no extranodal lesions in lung,gastrointestinal,liver and spleen,skin,etc.After strict exclusion of systemic lymphoma involvement in the bone marrow,the diagnosis was confirmed by bone marrow examination,5 cases were primary myeloid diffuse large B-cell lymphoma and 1 case was primary myeloid peripheral T-cell lymphoma(NOS).1 case abandoned treatment,5 cases received CHOP-like or combined R regimen,including 1 case of autologous stem cell transplantation.4 cases died and 2 case survived.The median OS was 5.5(1-36)months.Conclusion:The prognosis of primary marrow lymphoma is poor,and bone marrow-related examination is an important means of diagnosis.Diffuse large B-cell lymphoma is the most common histomorphologic and immune subtype,and autologous hematopoietic stem cell transplantation may improve the prognosis.