Alzheimer’s disease (AD) is a chronic neurodegenerative disorder that severely affects the health of the elderly, marked by its incurability, high prevalence, and extended latency period. The current approach to AD prevention and treatment emphasizes early detection and intervention, particularly during the pre-AD stage of mild cognitive impairment (MCI), which provides an optimal “window of opportunity” for intervention. Clinical detection methods for MCI, such as cerebrospinal fluid monitoring, genetic testing, and imaging diagnostics, are invasive and costly, limiting their broad clinical application. Speech, as a vital cognitive output, offers a new perspective and tool for computer-assisted analysis and screening of cognitive decline. This is because elderly individuals with cognitive decline exhibit distinct characteristics in semantic and audio information, such as reduced lexical richness, decreased speech coherence and conciseness, and declines in speech rate, voice rhythm, and hesitation rates. The objective presence of these semantic and audio characteristics lays the groundwork for computer-based screening of cognitive decline. Speech information is primarily sourced from databases or collected through tasks involving spontaneous speech, semantic fluency, and reading, followed by analysis using computer models. Spontaneous language tasks include dialogues/interviews, event descriptions, narrative recall, and picture descriptions. Semantic fluency tasks assess controlled retrieval of vocabulary items, requiring participants to extract information at the word level during lexical search. Reading tasks involve participants reading a passage aloud. Summarizing past research, the speech characteristics of the elderly can be divided into two major categories: semantic information and audio information. Semantic information focuses on the meaning of speech across different tasks, highlighting differences in vocabulary and text content in cognitive impairment. Overall, discourse pragmatic disorders in AD can be studied along three dimensions: cohesion, coherence, and conciseness. Cohesion mainly examines the use of vocabulary by participants, with a reduction in the use of nouns, pronouns, verbs, and adjectives in AD patients. Coherence assesses the ability of participants to maintain topics, with a decrease in the number of subordinate clauses in AD patients. Conciseness evaluates the information density of participants, with AD patients producing shorter texts with less information compared to normal elderly individuals. Audio information focuses on acoustic features that are difficult for the human ear to detect. There is a significant degradation in temporal parameters in the later stages of cognitive impairment; AD patients require more time to read the same paragraph, have longer vocalization times, and produce more pauses or silent parts in their spontaneous speech signals compared to normal individuals. Researchers have extracted audio and speech features, developing independent systems for each set of features, achieving an accuracy rate of 82% for both, which increases to 86% when both types of features are combined, demonstrating the advantage of integrating audio and speech information. Currently, deep learning and machine learning are the main methods used for information analysis. The overall diagnostic accuracy rate for AD exceeds 80%, and the diagnostic accuracy rate for MCI also exceeds 80%, indicating significant potential. Deep learning techniques require substantial data support, necessitating future expansion of database scale and continuous algorithm upgrades to transition from laboratory research to practical product implementation.

Hepatitis B is a major global public health issue. Through the implementation of comprehensive prevention and control strategies centered on hepatitis B vaccination， China has achieved remarkable progress in hepatitis B prevention and control， while there are still many issues and challenges. This article reviews the development of hepatitis B vaccination strategies in China， analyzes the goal and advances in vaccination in different populations， and problems and challenges， in order to provide a reference for further optimizing vaccination strategies and improving the levels of prevention and control.

Objective To evaluate the radiation impact of a self-developed digital miniature CT on the human body and the environment under simulated scanning conditions, and verify its safety and regulatory compliance. Methods Under typical head scanning conditions with the digital miniature CT (70 kV/10 mA), the equivalent doses received at the body surface sites corresponding to the thyroid, breast, stomach, liver, kidney, and gonads of the phantom were measured without protection and with 0.5 mmPb equivalent protection using LiF (Mg, Cu, P) thermoluminescent dosimeters. The ambient dose equivalent rates at the bed level inside the CT room at different directions and distances from the scanning center were measured using a model AT1121 X/γ dosimeter. The equivalent doses of organs on both sides of the phantom and the ambient equivalent dose rates on the left and right sides of the longitudinal axis of the bed in the CT room were compared. The Mann-Whitney test was used at a significance level of P < 0.05. Results During a single scan of the head with the digital miniature CT, the equivalent doses at the body surface sites corresponding to the thyroid, breast, stomach, liver, kidney, and gonads without protection were 1.04, 0.95, 0.55, 0.57, 0.40, and 0.12 mSv, respectively, which were only 0.84% to 8.24% of the doses inside the irradiation field. With 0.5 mm Pb equivalent protection, the equivalent dose of the thyroid decreased from 8.24 mSv to 3.27 mSv with a reduction of 60.3%, and the doses of the other organs were reduced to 1.5-11.5 μSv with the maximum reduction of 14 times. In the longitudinal axis direction of the CT bed, the ambient dose equivalent rate at a distance of 2 m from the scanning center was reduced to 0.066 mSv/h, which was only 9.6% of the ambient equivalent dose rate at a distance of 50 cm from the scanning center. Conclusion The digital miniature CT has advantages in ensuring patient safety, optimizing imaging quality, and promoting technological development, demonstrating promising application potential. However, the radiation protection of personal and CT room should not be ignored.

The chemical constituents of Commiphora myrrha was investigated by column chromatography on silica gel, ODS, Sephadex LH-20, and semi-preparative HPLC. Their structures were elucidated by comprehensive spectroscopic methods including UV, IR, MS, NMR, as well as ECD calculation. Seven compounds were isolated from the dichloromethane-soluble fraction of C. myrrha and their structures were identified as(1S,2R,4S,5R,8S)-guaiane-2-hydroxy-7(11),10(15)-dien-6-oxo-12,8-olide(1), commipholide E(2), myrrhterpenoid H(3), myrrhterpenoid I(4), myrrhterpenoid E(5), 2α-methoxy-8α-hydroxy-6-oxogermacra-1(10),7(11)-dien-8,12-olide(6), 8,12-epoxy-1α,9α-hydroxy-eudesma-7,11-diene-6-dione(7). Compound 1 was a new compound and named myrrhterpenoid P. Compound 7 was isolated from Commiphora genus for the first time. Compounds 2, 5, and 6 significantly inhibited nitric oxide(NO) production in LPS-stimulated RAW264.7 cells, with IC_(50) values of(49.67±4.16),(40.80±1.27),(47.22±0.87) μmol·L~(-1), respectively [indomethacin as the positive control, with IC_(50) value of(63.92±2.60) μmol·L~(-1)].
Commiphora/chemistry* ; Animals ; Mice ; Resins, Plant/chemistry* ; Sesquiterpenes/isolation & purification* ; Molecular Structure ; Nitric Oxide ; Macrophages/metabolism* ; RAW 264.7 Cells ; Drugs, Chinese Herbal/pharmacology*

The chemical components of Carthami Flos were investigated by using macroporous resin, silica gel column chromatography, reversed-phase octadecylsilane(ODS) column chromatography, Sephadex LH-20, and semi-preparative high-performance liquid chromatography(HPLC). The planar structures of the compounds were established based on their physicochemical properties and ultraviolet-visible(UV-Vis), infrared(IR), high-resolution electrospray ionization mass spectrometry(HR-ESI-MS), and nuclear magnetic resonance(NMR) spectroscopic technology. The absolute configurations were determined by comparing the calculated and experimental electronic circular dichroism(ECD). Six flavonoid C-glycosides were isolated from the 30% ethanol elution fraction of macroporous resin obtained from the 95% ethanol extract of Carthami Flos, and identified as saffloquinoside F(1), 5-hydroxysaffloneoside(2), iso-5-hydroxysaffloneoside(3), isosafflomin C(4), safflomin C(5), and vicenin 2(6). Among these, the compounds 1 to 3 were new chalcone C-glycosides. The compounds 1, 2, 4, and 5 could significantly increase the viability of H9c2 cardiomyocytes damaged by oxygen-glucose deprivation/reoxygenation(OGD/R) at a concentration of 50 μmol·L~(-1), showing their good cardioprotective activity.
Glycosides/pharmacology* ; Flowers/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Carthamus tinctorius/chemistry* ; Chalcones/pharmacology* ; Animals

OBJECTIVE: To establish an in vitro cell model simulating acute graft-versus-host disease (aGVHD) bone marrow microenvironment injury with the advantage of mouse serum of aGVHD model and explore the effect of serum of aGVHD mouse on the adipogenic differentiation ability of mesenchymal stem cells (MSCs). METHODS: The 6-8-week-old C57BL/6N female mice and BALB/c female mice were used as the donor and recipient mice of the aGVHD model, respectively. Bone marrow transplantation (BMT) mouse model (n=20) was established by being injected with bone marrow cells (1×10⁷ per mouse) from donor mice within 4-6 hours after receiving a lethal dose (8.0 Gy, 72.76 cGy/min) of γ ray general irradiation. A mouse model of aGVHD (n=20) was established by infusing a total of 0.4 ml of a mixture of donor mouse-derived bone marrow cells (1×10⁷ per mouse) and spleen lymphocytes (2×10⁶ per mouse). The blood was removed from the eyeballs and the mouse serum was aspirated on the 7^th day after modeling. Bone marrow-derived MSCs were isolated from 1-week-old C57BL/6N male mice and incubated with 2%, 5% and 10% BMT mouse serum and aGVHD mouse serum in the medium, respectively. The effect of serum in the two groups on the in vitro adipogenic differentiation ability of mouse MSCs was detected by Oil Red O staining. The expression levels of related proteins PPARγ and CEBPα were detected by Western blot. The expression differences of key adipogenic transcription factors including PPARγ, CEBPα, FABP4 and LPL were determined by real-time quantitative PCR (RT-qPCR). RESULTS: An in vitro cell model simulating the damage of bone marrow microenvironment in mice with aGVHD was successfully established. Oil Red O staining showed that the number of orange-red fatty droplets was significantly reduced and the adipogenic differentiation ability of MSC was impaired at aGVHD serum concentration of 10% compared with BMT serum. Western blot experiments showed that adipogenesis-related proteins PPARγ and CEBPα expressed in MSCs were down-regulated. Further RT-qPCR assay showed that the production of PPARγ, CEBPα, FABP4 and LPL, the key transcription factors for adipogenic differentiation of MSC, were significantly reduced. CONCLUSION The adipogenic differentiation capacity of MSCs is inhibited by aGVHD mouse serum.
Animals ; Mesenchymal Stem Cells/cytology* ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Adipogenesis ; Female ; Cell Differentiation ; Graft vs Host Disease/blood* ; Bone Marrow Cells/cytology* ; PPAR gamma/metabolism* ; Disease Models, Animal ; CCAAT-Enhancer-Binding Protein-alpha/metabolism*

To optimize the formulation and technology of oxymatrine-astragaloside IV coloaded liposomes (Om-As-Lip) based on quality by design (QbD) principles, and further to verify the feasibility of its amplification process, Om-As-Lip was prepared by ethanol injection combined with pH gradient method. The critical material attributions of Om-As-Lip were evaluated by dual-risk analysis tools and Plackett-Burman design (PBD). The formulation of Om-As-Lip was further optimized with the Box-Behnken design (BBD). The design space was also established based on the contour plots of BBD. In order to further investigate the amplification process of Om-As-Lip, the critical process parameters of high-pressure homogenization (HPH) were optimized by single-factor test, and the quality of the final product was also evaluated. The results of risk analysis and PBD confirmed that the astragaloside concentration, cholesterol concentration, and phospholipid ratio (HSPC∶SPC) were the ctitical material attributes. The model established by BBD had a good predictability, and the optimized mass ratio of As to phospholipids was 1∶40, cholesterol to phospholipids was 1∶10, HSPC to SPC was 51∶9. The design space of Om-As-Lip was as follows: the ratio of cholesterol to phospholipids was 1∶12-1∶5 and HSPC to SPC was 1∶7-17∶3. The optimized high-pressure homogenization pressure was 600 bar, temperature was 4 ℃, and cycle times was 6 times for HPH-Om-As-Lip. The quality of Om-As-Lip prepared based on the QbD concept can meet the expected CQAs, and the formulation and technology established can provide a reliable experimental basis for its future development and applications.

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated.Results:666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion:CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).

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 report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive bacteria from blood cultures in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units，and the top five bacteria were Staphylococcus aureus（ n=1 147，36.3%），coagulase-negative Staphylococci（ n=928，29.3%）， Enterococcus faecalis（ n=369，11.7%）， Enterococcus faecium（ n=296，9.4%）and alpha-hemolyticus Streptococci（ n=192，6.1%）. The detection rates of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）were 26.4%（303/1 147）and 66.7%（619/928），respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome，rifampin，compound sulfamethoxazole，linezolid，minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%（2/369），and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions（ χ2=14.578， P=0.002），while the detection rate of MRCNS in northern China was significantly higher than that in other regions（ χ2=15.195， P=0.002）. The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals（ χ2=13.519 and 12.136， P<0.001）. The detection rates of MRSA and MRCNS in economically more advanced regions（per capita GDP≥92 059 Yuan in 2022）were higher than those in economically less advanced regions（per capita GDP<92 059 Yuan）（ χ2=9.969 and 7.606， P=0.002和0.006）. Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China， Staphylococci is the most common while the MRSA incidence decreases continuously with time；the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China，with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.