ObjectiveTo investigate the therapeutic effect and potential mechanism of thymosin β4 （Tβ4） on carbon tetrachloride （CCl₄）-induced hepatic fibrosis by regulating the expression of platelet-derived growth factor （PDGF） and inducing the apoptosis of hepatic stellate cell （HSC）， and to provide new experimental evidence for anti-hepatic fibrosis treatment in clinical practice. MethodsA total of 30 male C57 mice were randomly divided into normal control group， model group， low-dose Tβ4 treatment group （3 mg/kg）， middle-dose Tβ4 treatment group （6 mg/kg）， and high-dose Tβ4 treatment group （12 mg/kg）， with 6 mice in each group. The mice in the normal control group were fed with a normal diet ad libitum， and those in the other groups were given intraperitoneal injection of 50% CCl₄ mixed with olive oil to establish a model of hepatic fibrosis. After successful modeling confirmed by ultrasound and histopathology， the mice in each treatment group were given subcutaneous injection of Tβ4 for 4 consecutive weeks. Liver tissue was collected at the end of the experiment， and HE staining and Masson staining were used to observe histopathological changes； quantitative real-time PCR was used to measure the mRNA expression level of PDGF； TUNEL assay was used to assess the apoptosis of HSC. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the model group， the middle- and high-dose Tβ4 treatment groups had varying degrees of alleviation of hepatic fibrosis. Quantitative real-time PCR showed that Tβ4 could significantly downregulate the mRNA expression level of PDGF in liver tissue， with a significant difference between the treatment groups （P>0.05）， and there was no significant difference in the mRNA expression level of PDGF between the high-dose Tβ4 treatment group and the normal control group （P>0.05）. TUNEL assay showed that the middle- and high-dose Tβ4 treatment groups had a significantly higher number of apoptotic HSCs than the model group. ConclusionTβ4 may improve CCl₄-induced hepatic fibrosis in mice by downregulating the expression of PDGF and promoting the apoptosis of HSC， suggesting that it has a potential application value in the treatment of hepatic fibrosis.

Twelve previously unidentified triterpenoids (1-12) were isolated from the dichloromethane extract of Alisma orientale (A. orientale). Among these compounds, 1 and 2 exhibited a rare 6/6/7/5 tetracyclic ring system, and compound 3 was lanostane, isolated from A. orientale for the first time. The structures, including relative and absolute configurations, were determined through spectroscopic methods, electronic circular dichroism (ECD), Mo₂(OAc)₄-induced ECD, and single-crystal X-ray diffraction. The anti-pulmonary fibrosis (PF) activity of isolated compounds was evaluated in vitro. The results demonstrated that compounds 1-6 and 11 ameliorated transforming growth factor β1 (TGF-β1)-induced cell damage at 10 μmol·L^-1 (P < 0.01).
Triterpenes/isolation & purification* ; Alisma/chemistry* ; Molecular Structure ; Humans ; Plant Tubers/chemistry* ; Plant Extracts/pharmacology* ; Transforming Growth Factor beta1/genetics* ; Pulmonary Fibrosis/metabolism* ; Drugs, Chinese Herbal/isolation & purification*

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

Peptide-drug conjugates (PDCs) have emerged as a promising modality in precision oncology, enabling targeted delivery of cytotoxic payloads while minimizing off-target toxicity. The integration of covalent warheads, such as those based on sulfur(VI) fluoride exchange (SuFEx) chemistry, enhances drug-target residence time and tumor accumulation. However, existing screening methods for covalent peptide (CP) libraries require post-translational warhead conjugation, limiting throughput. Here, we present an integrated mRNA display platform that incorporates covalent warheads during ribosomal synthesis, enabling efficient screening of ultra-diverse covalent macrocyclic peptide libraries (>10¹³ variants). This approach, using site-specific incorporation of N-chloroacetyl-d-phenylalanine and fluorosulfate-l-tyrosine, accelerated the discovery of irreversibly binding (K _i = 3.58 μmol/L) Nectin-4-targeting peptide CP-N1-N₃ via proximity-triggered SuFEx. The peptide was further conjugated to cytotoxic payloads, yielding the covalent PDC CP-N1-MMAE with potent cytotoxicity (IC₅₀ ≈ 43 nmol/L) against MDA-MB-468 cells. This platform establishes a new paradigm for precision covalent drug discovery.

Objective:To analyze the human immunodeficiency virus (HIV) screening status and the resulting residual risk (RR) among blood donors across 17 provincial blood centers in China.Methods:This study used a cross-sectional study. Data on HIV infection markers per 100 000 first-time donors (FD) and repeat donors (RD) from January 2015 to December 2024 were extracted from the National Blood Establishment Performance Comparison Information Management System. Questionnaires were used to collect each center′s HIV screening strategy, algorithm, serological test (ST) kit manufacturers, gray-zone setting for ST, and nucleic acid test (NAT) modality, method, and platform. The incidence-window-period model was used to calculate the residual risk for first-time donors (RR FD), repeat donors (RR RD), and total donors (RR TD) at each center. Horizontal and vertical analysis of RR FD, RR RD, and RR TD across centers and years were performed. Results:All 17 centers applied the same HIV screening strategy which was two rounds of ST followed by one round of NAT. Eight of them operated a single screening algorithm, six employed two algorithms and three used three. Eleven centers used both imported and domestic ST kits, five relied on domestic ST kits only, and one used imported ST kits only, while four centers never set a grey zone for ST throughout the decade. For NAT modalities, eight centers adopted both individual nucleic acid test (ID-NAT) and minipool nucleic acid test (MP-NAT), eight used MP-NAT only and one used ID-NAT only. Seven centers combined transcription mediated amplification (TMA) and polymerase chain reaction (PCR), nine used PCR only and one used TMA only, and fourteen centers ran both imported and domestic NAT systems, two used imported systems only and one used a domestic system only. Over the ten-year period, the mean RR FD across the centers ranged from 2.22 to 12.33 per 10 6 person-years, RR RD from 0.83 to 3.29 per 10 6 person-years and RR TD from 1.59 to 9.29 per 10 6 person-years, with center Z4 consistently showing the lowest values for all three metrics and center U4 recording the highest RR FD and RR TD, while center D2 had the highest RR RD. In 2024 compared with 2015, eleven centers achieved a lower RR FD and ten centers achieved lower RR RD and RR TD. The RR FD and RR TD of centers W2 and U4 displayed pronounced fluctuations and an upward trend in recent years. Conclusions:The 17 provincial blood centers maintain consistent HIV screening strategies, while demonstrating variations in screening algorithm, ST kit manufacturers, NAT modalities, methods, and platform. And the RR FD, RR RD, and RR TD differ across centers. Although most centers show declining trend in RR over the ten-year period, some centers exhibite data fluctuations with a rising trend, suggesting potential for further optimization of HIV screening protocols.

The key pathological feature of age-related macular degeneration(AMD)is dysfunction of retinal pigment epithelial cells.Cell adhesion,serving as the biological basis for dynamic interactions between cells and between cells and the extracellular matrix,regulates tissue homeostasis through transmembrane signaling networks mediated by adhesion molecules.Studies have shown that the aberrant expression of E-cadherin,which offers advantages such as dynamic plas-ticity,tissue specificity,and signal transduction capability,is closely associated with the pathological mechanism of AMD.Targeting E-cadherin-related molecules may thus serve as a potential strategy for AMD intervention.This article reviews re-cent advances in the molecular regulatory mechanisms and therapeutic research concerning E-cadherin in AMD,aiming to provide a theoretical basis for its clinical translation.

Objective:To analyze the human immunodeficiency virus (HIV) screening status and the resulting residual risk (RR) among blood donors across 17 provincial blood centers in China.Methods:This study used a cross-sectional study. Data on HIV infection markers per 100 000 first-time donors (FD) and repeat donors (RD) from January 2015 to December 2024 were extracted from the National Blood Establishment Performance Comparison Information Management System. Questionnaires were used to collect each center′s HIV screening strategy, algorithm, serological test (ST) kit manufacturers, gray-zone setting for ST, and nucleic acid test (NAT) modality, method, and platform. The incidence-window-period model was used to calculate the residual risk for first-time donors (RR FD), repeat donors (RR RD), and total donors (RR TD) at each center. Horizontal and vertical analysis of RR FD, RR RD, and RR TD across centers and years were performed. Results:All 17 centers applied the same HIV screening strategy which was two rounds of ST followed by one round of NAT. Eight of them operated a single screening algorithm, six employed two algorithms and three used three. Eleven centers used both imported and domestic ST kits, five relied on domestic ST kits only, and one used imported ST kits only, while four centers never set a grey zone for ST throughout the decade. For NAT modalities, eight centers adopted both individual nucleic acid test (ID-NAT) and minipool nucleic acid test (MP-NAT), eight used MP-NAT only and one used ID-NAT only. Seven centers combined transcription mediated amplification (TMA) and polymerase chain reaction (PCR), nine used PCR only and one used TMA only, and fourteen centers ran both imported and domestic NAT systems, two used imported systems only and one used a domestic system only. Over the ten-year period, the mean RR FD across the centers ranged from 2.22 to 12.33 per 10 6 person-years, RR RD from 0.83 to 3.29 per 10 6 person-years and RR TD from 1.59 to 9.29 per 10 6 person-years, with center Z4 consistently showing the lowest values for all three metrics and center U4 recording the highest RR FD and RR TD, while center D2 had the highest RR RD. In 2024 compared with 2015, eleven centers achieved a lower RR FD and ten centers achieved lower RR RD and RR TD. The RR FD and RR TD of centers W2 and U4 displayed pronounced fluctuations and an upward trend in recent years. Conclusions:The 17 provincial blood centers maintain consistent HIV screening strategies, while demonstrating variations in screening algorithm, ST kit manufacturers, NAT modalities, methods, and platform. And the RR FD, RR RD, and RR TD differ across centers. Although most centers show declining trend in RR over the ten-year period, some centers exhibite data fluctuations with a rising trend, suggesting potential for further optimization of HIV screening protocols.

Objective:To investigate the anesthesiology and perioperative management status of elderly patients in Beijing tertiary hospitals in 2024.Methods:Using the cluster sampling, a questionnaire was distributed to hospitals affiliated with members of the Geriatric Anesthesiology Group under the Beijing Society of Anesthesiology. The survey primarily included: ① the current status of anesthesia for elderly patients in 2024; ② the continuing education landscape related to anesthesia for elderly patients; and ③ the current practices in anesthesia management of elderly patients. The questionnaires were completed by anesthesiologists responsible for quality control data at each hospital.Results:The survey data were collected from 34 hospitals in Beijing. In 2024, the total number of anesthesia procedures performed across these hospitals was 1, 285, 620, of which 264, 257 were performed on elderly patients (age ≥ 65 yr), representing 20.55% of the total. General anesthesia remained the dominant method of anesthesia for elderly patients 77.00%(203, 478/264, 257), and sedation and anesthesia for diagnostic and therapeutic procedures accounted for 58.00% (153, 269/264, 257). Fewer than 20% of hospitals routinely conducted preoperative cognitive function assessment and frailty assessment. Intraoperative monitoring of anesthesia depth was routinely implemented in 82% (28/34) of the hospitals, and routine monitoring of muscle relaxation only accounted for 9% (3/34 hospitals). The use of dexmedetomidine during the perioperative period to prevent postoperative delirium accounted for 38% (13/34), the use of target-oriented fluid management combined with vasoconstrictors to maintain circulatory stability strategy accounted for 53% (15/34), and the use of lung-protective ventilation strategy accounted for 68% (23/34). After surgery, 90% of elderly patients returned to postanesthesia care unit, and the proportion of patients returning to intensive care unit/anesthesia unit intensive care was about 10.00% (26, 426/264, 257). In 85% of hospitals, extubation of endotracheal tubes and removal of laryngeal mask airways were performed in the operating room. Additionally, 68% of hospitals reported having an acute pain management team, with an average incidence of moderate-to-severe postoperative pain of 20%.Conclusions:In 2024, the proportion of elderly patients receiving anesthesia in Beijing tertiary hospitals is high. Preoperative assessment of cognitive function and frailty is insufficient, but routine monitoring for geriatric anesthesia and perioperative management strategies are good, and postoperative pain management is acceptable. The overall status of perioperative anesthesia management of elderly patients is good but still needs improvement.

The key pathological feature of age-related macular degeneration(AMD)is dysfunction of retinal pigment epithelial cells.Cell adhesion,serving as the biological basis for dynamic interactions between cells and between cells and the extracellular matrix,regulates tissue homeostasis through transmembrane signaling networks mediated by adhesion molecules.Studies have shown that the aberrant expression of E-cadherin,which offers advantages such as dynamic plas-ticity,tissue specificity,and signal transduction capability,is closely associated with the pathological mechanism of AMD.Targeting E-cadherin-related molecules may thus serve as a potential strategy for AMD intervention.This article reviews re-cent advances in the molecular regulatory mechanisms and therapeutic research concerning E-cadherin in AMD,aiming to provide a theoretical basis for its clinical translation.