In recent years, the application of artificial intelligence (AI) in the field of biology has witnessed remarkable advancements. Among these, the most notable achievements have emerged in the domain of protein structure prediction and design, with AlphaFold and related innovations earning the 2024 Nobel Prize in Chemistry. These breakthroughs have transformed our ability to understand protein folding and molecular interactions, marking a pivotal milestone in computational biology. Looking ahead, it is foreseeable that the accurate prediction of various physicochemical properties of proteins—beyond static structure—will become the next critical frontier in this rapidly evolving field. One of the most important protein properties is thermodynamic stability, which refers to a protein’s ability to maintain its native conformation under physiological or stress conditions. Accurate prediction of protein stability, especially upon single-point mutations, plays a vital role in numerous scientific and industrial domains. These include understanding the molecular basis of disease, rational drug design, development of therapeutic proteins, design of more robust industrial enzymes, and engineering of biosensors. Consequently, the ability to reliably forecast the stability changes caused by mutations has broad and transformative implications across biomedical and biotechnological applications. Historically, protein stability was assessed via experimental methods such as differential scanning calorimetry (DSC) and circular dichroism (CD), which, while precise, are time-consuming and resource-intensive. This prompted the development of computational approaches, including empirical energy functions and physics-based simulations. However, these traditional models often fall short in capturing the complex, high-dimensional nature of protein conformational landscapes and mutational effects. Recent advances in machine learning (ML) have significantly improved predictive performance in this area. Early ML models used handcrafted features derived from sequence and structure, whereas modern deep learning models leverage massive datasets and learn representations directly from data. Deep neural networks (DNNs), graph neural networks (GNNs), and attention-based architectures such as transformers have shown particular promise. GNNs, in particular, excel at modeling spatial and topological relationships in molecular structures, making them well-suited for protein modeling tasks. Furthermore, attention mechanisms enable models to dynamically weigh the contribution of specific residues or regions, capturing long-range interactions and allosteric effects. Nevertheless, several key challenges remain. These include the imbalance and scarcity of high-quality experimental datasets, particularly for rare or functionally significant mutations, which can lead to biased or overfitted models. Additionally, the inherently dynamic nature of proteins—their conformational flexibility and context-dependent behavior—is difficult to encode in static structural representations. Current models often rely on a single structure or average conformation, which may overlook important aspects of stability modulation. Efforts are ongoing to incorporate multi-conformational ensembles, molecular dynamics simulations, and physics-informed learning frameworks into predictive models. This paper presents a comprehensive review of the evolution of protein thermodynamic stability prediction techniques, with emphasis on the recent progress enabled by machine learning. It highlights representative datasets, modeling strategies, evaluation benchmarks, and the integration of structural and biochemical features. The aim is to provide researchers with a structured and up-to-date reference, guiding the development of more robust, generalizable, and interpretable models for predicting protein stability changes upon mutation. As the field moves forward, the synergy between data-driven AI methods and domain-specific biological knowledge will be key to unlocking deeper understanding and broader applications of protein engineering.

Objective: Data on syncopal donation-related vasovagal reaction (DRVR) collected from 74 blood centers between 2020 and 2023 was statistically analyzed to provide a reference for developing preventive strategies against syncopal DRVR. Methods: Data on blood donation adverse reactions and basic information of donors from 2020 to 2023 were collected through the information management system at monitoring sentinel sites. Statistical analysis was performed on the following aspects of syncopal DRVR: characteristics of donors who experienced syncope, reported incidence, triggers, duration, presence and occurrence time of syncope-related trauma, clinical management including outpatient and inpatient treatment, and severity grading. Results: From 2020 to 2023, 45 966 donation-related adverse reactions were recorded. Of these, 1 665 (3.72%) cases were syncopal DRVR. The incidence of syncopal DRVR decreased with age, being the highest in the 18-22 age group. Incidence was significantly higher in female donors than male donors, in first-time donors than repeat donors, and in university and individual donors than group donors (all P<0.05). There was no statistically significant difference among different blood donation locations (P>0.05). The top three triggers were tension, fatigue, and needle phobia or fear of blood. Among syncopal DRVR cases, 60.36% occurred during blood collection, 87.63% lasted for less than 60 seconds, and 5.05% were accompanied by trauma. Notably, 57.14% of these traumas occurred after donor had left the blood collection site. Syncope severity was graded based on required treatment: grade 1 (fully recovered without treatment, 95.50%); grade 2 (recovered after outpatient treatment, 4.02%); and grade 3 (recovered after inpatient treatment, 0.48%). Conclusion: By analyzing the data of syncopal DRVR cases, it is possible to provide a reference for formulating blood donor safety policies.

[摘 要] 目的：探究芒柄花素调节JAK2/STAT3信号通路对胆囊癌细胞GBC-SD恶性生物学行为及血管生成的影响。方法：常规培养GBC-SD细胞并构建其移植瘤裸鼠，将GBC-SD细胞和其移植瘤裸鼠分为对照组、芒柄花素组、colivelin（JAK2/STAT3激活剂）组、芒柄花素 + colivelin组。用MTT法、Transwell实验和流式细胞术分别检测各组细胞的增殖、迁移和侵袭能力，以及凋亡，用ELISA法检测各组细胞血管内皮生长因子（VEGF）分泌水平，血管生成拟态（VM）形成实验检测各组细胞的成管腔能力，移植瘤实验检测芒柄花素对移植瘤生长的影响，免疫组化法检测各组移植瘤组织中CD31和VEGF表达，WB法检测各组细胞和移植瘤组织中JAK2/STAT3通路的磷酸化水平。结果：芒柄花素可明显抑制GBC-SD细胞的增殖、迁移和侵袭能力，促进其凋亡（均P < 0.05），抑制GBC-SD细胞分泌VEGF和VM形成（均P < 0.05），抑制GBC-SD细胞移植瘤的生长及血管生成（均P < 0.05），抑制移植瘤组织中VEGF表达，抑制GBC-SD细胞和其移植瘤组织中JAK2/STAT3通路的磷酸化，colivelin均可逆转芒柄花素的上述作用（均P < 0.05）。结论：芒柄花素通过抑制JAK2/STAT3信号通路抑制GBC-SD细胞增殖、迁移、侵袭、血管形成，促进其凋亡，JAK2/STAT3信号通路是胆囊癌临床治疗的潜在靶点。

OBJECTIVE To systematically evaluate the efficacy and safety of tislelizumab in the treatment of advanced non- small cell lung cancer （NSCLC）. METHODS Computerized searches were conducted in PubMed， Embase， the Cochrane Library， CNKI， Wanfang and other Chinese and English databases to collect randomized controlled trials （RCTs） on tislelizumab for advanced NSCLC. The search period was from the establishment of the databases to December 2024. After strictly screening the literature， extracting data and conducting quality evaluations in accordance with the inclusion and exclusion criteria， a meta-analysis was performed using RevMan 5.3 and Stata 16.0 software. RESULTS A total of 18 RCTs involving 2 337 patients were included， with 1 283 in the experimental group and 1 054 in the control group. The meta-analysis results showed that the objective response rate [RR＝1.61， 95%CI （1.48， 1.75）， P＜0.000 01]， disease control rate [RR＝1.21， 95%CI （1.13， 1.29）， P＜0.000 01]， progression free survival [HR＝0.55， 95%CI （0.45， 0.66）， P＜0.000 01]， and overall survival [HR＝0.78， 95%CI（0.62， 0.97）， P＝0.03] were significantly better in the experimental group than in the control group. There was no statistically significant difference in the incidence of adverse reactions between the two groups [RR＝1.00， 95%CI （0.73， 1.37）， P＝1.00]； among the common adverse reactions， only the incidence of liver function impairment was significantly higher in the experimental group than in the control group [RR＝1.30， 95%CI （1.10， 1.54）， P＜0.01]. CONCLUSIONS Tislelizumab in combination with chemotherapy or targeted drugs significantly improves the efficacy in patients with advanced NSCLC without increasing the risk of adverse reactions overall. However， liver function should be closely monitored during treatment.

OBJECTIVE: Based on the PTEN-induced hypothetical kinase 1 (PINK1)/Parkin pathway, the effect of acupuncture pretreatment on the expression of mitochondrial autophagy-related proteins in gastrocnemius muscle tissue of rats with exercise-induced muscle damage (EIMD) was observed, and the underlying mechanism of acupuncture pretreatment for the prevention and treatment of EIMD was explored. METHODS: Of 88 SD male rats, aged 6 weeks, 8 rats were randomly selected as a blank group, and the remaining 80 rats were randomized into a model group and an acupuncture pretreatment group, with 40 rats in each group. Either the model group or the acupuncture pretreatment group was subdivided randomly into 5 subgroups with 8 rats in each one according to the time points of sample collection, 0 h, 12 h, 24 h, 48 h and 72 h after modeling. An intermittent downhill running centrifugal exercise was carried out on an animal experimental treadmill to establish the EIMD model in the model group and the acupuncture pretreatment group. The rats in the acupuncture pretreatment group received acupuncture at "Guanyuan" (CV6) and bilateral "Zusanli" (ST36), once a day for 20 min each time, for 7 consecutive days before EIMD model preparation. Transmission electron microscopy was used to observe the ultrastructure of gastrocnemius muscle tissue in each group. The contents of malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) in serum were detected by ELISA. Western blot was used to detect the protein expression of PINK1, Parkin, sequestosome 1 (p62) and microtubule-associated protein light chain 3B (LC3B) in rat gastrocnemius muscle tissue. Real-time PCR was adopted to detect the mRNA expression of PINK1, Parkin, p62 and LC3B in rat gastrocnemius muscle tissue. RESULTS: Compared with the blank group, the mitochondria of gastrocnemius muscles showed obvious swelling in the 0 h, 12 h, 24 h, and 48 h model subgroups , autophagosomes were formed in the 12 h and 24 h model subgroups, and the mitochondrial morphology returned to normal gradually in the 72 h model subgroup. The serum MDA contents of rats in 5 model subgroups increased (P<0.01, P<0.05). The contents of SOD and CAT in the subgroups of 0 h, 12 h, 24 h and 48 h decreased (P<0.05, P<0.01). The protein and mRNA expression levels of PINK1, Parkin and LC3B in gastrocnemius muscle tissue of rats in 0 h, 12 h and 24 h subgroups were elevated (P<0.01); and the protein and mRNA expression levels of p62 in the 0 h, 12 h, 24 h and 48 h subgroups were reduced (P<0.01, P<0.05). Compared with the model subgroup at the same time point, the myofibril damage and the degree of mitochondrial swelling were mild in each acupuncture pretreatment subgroup, and the numbers of autophagosomes were fewer. The contents of MDA in the acupuncture pretreatment subgroups decreased at 0 h, 12 h, 24 h, and 48 h (P<0.05, P<0.01). The contents of SOD and CAT in the 12 h acupuncture pretreatment subgroup increased (P<0.05, P<0.01). The protein and mRNA expression levels of PINK1 and Parkin in the 0 h, 12 h, and 24 h acupuncture pretreatment subgroups decreased (P<0.01, P<0.05). The protein and mRNA expression levels of LC3B in the 12 h acupuncture pretreatment subgroup decreased (P<0.01), and that of p62 in the 0 h and 24 h acupuncture pretreatment subgroups increased (P<0.01, P<0.05). CONCLUSION The intermittent downhill running centrifugal exercise induces the excessive mitochondrial autophagy. Acupuncture pretreatment may attenuate EIMD, and the underlying mechanism is related to the regulation of PINK1/Parkin signaling pathway expression, reducing oxidative stress damage in skeletal muscle cells, and inhibiting mitochondrial autophagy overactivation.
Animals ; Ubiquitin-Protein Ligases/genetics* ; Male ; Rats ; Acupuncture Therapy ; Protein Kinases/genetics* ; Rats, Sprague-Dawley ; Mitophagy ; Humans ; Muscle, Skeletal/metabolism* ; Physical Conditioning, Animal ; Muscular Diseases/physiopathology* ; Signal Transduction

The chemical constituents in dried roots of Atractylodes macrocephala were investigated in this study. Through utilizing normal-phase silica gel and ODS column chromatography, TLC, and semi-preparative HPLC, 4 new sesquiterpenoids were purified from the ethyl acetate extract of A. macrocephala. By various spectroscopic techniques, such as 1D and 2D NMR, HR-ESI-MS, IR, UV, and CD, their structures were identified as atractylmacron A (1), 9β-hydroxyasterolide (2), atractylenolide H (3), atractylenolide J (4). Compound 1 possesses a rare 6/7 bicyclic skeleton.

This paper summarizes Professor HAN Mingxiang's clinical experience in treating chronic obstructive pulmonary disease （COPD）. He believes that the key pathomechanism of COPD in the acute exacerbation stage is the invasion of external pathogens triggering latent illness， while lung qi deficiency is the primary mechanism in the stable stage. The core pathological factors throughout disease progression are deficiency， phlegm， and blood stasis. Treatment emphasizes a staged and syndrome-based approach. During the acute exacerbation stage， for wind-cold invading the lung syndrome， the self-formulated Sanzi Wenfei Decoction （三子温肺汤） is used to relieve the exterior， dispel cold， warm the lung， and resolve phlegm. For phlegm-dampness obstructing the lung syndrome， Huatan Jiangqi Fomulation （化痰降气方） is prescribed to warm the lung， transform phlegm， descend qi， and calm wheezing. For phlegm-heat obstructing the lung syndrome， Qingfei Huatan Fomulation （清肺化痰方） is applied to clear heat， resolve phlegm， moisten the lung， and stop coughing. For phlegm and blood stasis interlocking syndrome， Qibai Pingfei Fomulation （芪白平肺方） is used to tonify qi， resolve phlegm， and activate blood circulation to remove stasis. During the stable stage， for lung qi deficiency syndrome， Shenqi Wenfei Decoction （参芪温肺汤） is employed to warm the lung， tonify qi， resolve phlegm， and eliminate turbidity. For lung-spleen qi deficiency syndrome， Shenqi Buzhong Decoction （参芪补中汤） is utilized to strengthen the spleen， tonify qi， and reinforce metal （lung） from earth （spleen）. For lung-kidney deficiency syndrome， Shenqi Tiaoshen Fomulation （参芪调肾方） is prescribed to tonify the lung， warm yang， and regulate kidney function to calm wheezing. These strategies provide insights into the traditional Chinese medicine treatment of COPD.

Objective To develop and validate a scoring system to predict the possibility of laparoscopic cholecystectomy (LC) conversion to laparotomy based on preoperative clinical data, and to establish a grading management model of surgery. Methods A retrospective analysis was conducted on the clinical data of 9 414 patients who underwent LC at Renhe Hospital and Huashan Hospital from June 2013 to June 2018. The patients were divided into two groups: the LC group (9 246 patients who successfully underwent LC) and the conversion to laparotomy group (168 patients who required conversion to open surgery). The data of two groups were compared, and the risk factors affecting conversion to laparotomy were screened out by single factor analysis of Chi-square test. Then, the risk factors were analyzed by multiple Logistic regression, and the pre-coefficient of each variable of the risk factors was assigned according to the established conversion to laparotomy possibility function. After calculating the score of each case, the difference in the actual conversion rate of each group was compared. The area under receiver operating characteristic (ROC) curve was calculated to evaluate the performance of the scoring system. According to the scoring system, LC surgical grading management model was created and verified. Results The following factors were identified as significant risk factors for conversion to laparotomy (P < 0.001): body temperature ≥ 38.5℃, frequency of acute cholecystitis ≥3 times, maximum thickness of gallbladder wall ≥ 5 mm, gallbladder neck stone incarceration, diameter of common bile duct ≥8 mm, and surgical experience ≤50 cases were the risk factors for conversion to laparotomy (P < 0.001). A score >3 points was associated with a high risk of conversion to laparotomy. Conclusions The LC scoring system and surgical grading management are reliable and effective tools for predicting and reducing the conversion rate of LC to laparotomy.

Neoadjuvant therapy for pancreatic cancer is undergoing a paradigm shift from conventional chemotherapy to precision medicine. This expert forum discussed cutting-edge issues in pancreatic cancer neoadjuvant therapy from an evidence-based perspective, incorporating the latest clinical research advances. We focused on innovative directions including immunotherapy combination strategies, liquid biopsy applications, artificial intelligence (AI)-assisted decision making, and individualized precision medicine. We proposed forward-looking concepts such as molecular subtyping-guided individualized treatment strategies, multi-omics integrated efficacy prediction models, and standardized multidisciplinary collaborative care systems. These innovative concepts will drive pancreatic cancer neoadjuvant therapy toward more precise and effective directions.