OBJECTIVE To conduct a clinical rapid evaluation of the marketed proprotein convertase subtilisin/kexin type 9 （PCSK9） inhibitors in China， including evolocumab， tafolecimab， recaticimab， ebronucimab， ongericimab and inclisiran. METHODS Based on the Rapid Guide for Drug Evaluation and Selection in Chinese Medical Institutions （second edition）， drug instructions， clinical diagnosis and treatment guidelines， and literature for six drugs were retrieved from CNKI， Wanfang Data， VIP， PubMed， Embase， Cochrane Library and related official websites. The clinical rapid evaluation was conducted from five aspects： pharmaceutical characteristics， effectiveness， safety， economy， and other attributes. RESULTS The pharmaceutical characteristics， effectiveness， safety， economy， other attributes， and total score of evolocumab scored 24， 27， 15.7， 10， 5.3， and 82 points， respectively. Tafolecimab scored 23.5， 23， 11.5， 9.97， 4.6， and 72.57 points， respectively. Recaticimab scored 20.5， 22， 15.5， 6.37， 3.5， and 67.87 points. Ebronucimab scored 20， 23， 11， 6.48， 3.5， and 63.98 points. Ongericimab scored 20.5， 23， 8.5， 4.83， 3.5， and 60.33 points. Inclisiran scored 25.5， 24， 13， 6.48， 5， and 73.98 points. CONCLUSIONS Evolocumab is the optimal choice for treating hypercholesterolemia and is recommended as the first-line option. Tafolecimab is the second-line option， and recaticimab is suitable for patients who are sensitive to drug adverse reactions. Inclisiran is suitable for patients with poor compliance. Ebronucimab and ongericimab are weakly recommended due to their later market introduction. Clinicians should make individualized drug selections based on factors such as patient risk level and compliance requirements.

OBJECTIVE To evaluate the cost-effectiveness of cefiderocol versus best available therapy （BAT） or standard-of- care （SOC） for the treatment of confirmed or suspected carbapenem-resistant Gram-negative bacterial （CRGNB） serious infections from the perspective of the Chinese healthcare system， and to explore its reasonable pricing. METHODS A decision tree model was constructed based on data from two phase Ⅲ clinical trials （CREDIBLE-CR and GAME CHANGER） to simulate the cost- effectiveness of cefiderocol in two scenarios： salvage therapy for confirmed CRGNB infection （scenario 1） and empirical therapy for suspected CRGNB infection （scenario 2）. The primary outcome measure was the incremental cost-effectiveness ratio （ICER）. The willingness-to-pay （WTP） was set at 1 to 3 times China’s per capita GDP in 2024. To verify the robustness of the results， one- way and probabilistic sensitivity analyses were conducted， and based on these， a reasonable price range for cefiderocol in the Chinese market was explored. RESULTS The results for scenario 1 showed that the clinical cure rate in the cefiderocol group was higher than that in the BAT group （47.50% vs. 34.21%）， but its ICER was 415 065.03 yuan per cured case， exceeding three times China’s GDP per capita. Scenario 2 revealed that the ICER for cefiderocol relative to SOC was as high as 1 362 446.16 yuan per cured case， far exceeding the WTP. Sensitivity analysis indicated that the treatment duration and price of cefiderocol were key factors affecting its cost-effectiveness. In the two scenarios described above， the unit price of cefiderocol must fall below 683.47 and 242.00 yuan/g， respectively， to be considered cost-effective. CONCLUSIONS Based on the current market price， cefiderocol lacks sufficient cost-effectiveness for treating confirmed or suspected CRGNB serious infections within China’s healthcare system. To improve its accessibility， price negotiations or a tiered medical insurance payment strategy are required.

OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors （DTIs） in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital （the Affiliated Hospital of UESTC）， a multidisciplinary working group was established. Through literature review and the Delphi method， clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework； systematic searches were conducted in CNKI， Medline， Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations （each with an expert consensus rate exceeding 90%） on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection， dosing ranges， key monitoring points， and safety management strategies for parenteral DTIs in various scenarios， including the perioperative period of ventricular assist device implantation， the perioperative period of cardiac surgery， perioperative patients with lower-extremity atherosclerotic disease， the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome， the perioperative period of carotid artery stenting in patients with carotid stenosis， the perioperative period of patients with right heart thrombosis， and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition， warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.

ObjectiveTo explore the clinical efficacy and safety of Da Chaihutang （DCH） for the treatment of sepsis with Yang syndrome. MethodsA total of 70 patients suffering from sepsis with Yang syndrome were randomly divided into an observation group and a control group， with 35 cases in each group. They both received standard Western medicine treatment. The observation group was additionally given a dose of DCH， which was boiled into 100 mL and taken twice. The control group was additionally given an equal volume and dosage of warm water. The intervention lasted for three days. The 28-day all-cause mortality and the changes in the following indicators before and after intervention were compared between the two groups， including sequential organ failure assessment （SOFA）， acute physiology and chronic health evaluation Ⅱ （APACHE Ⅱ） score，white blood cell （WBC），the percentage of neutrophils （NEU%），C-reactive protein （CRP），procalcitonin （PCT），alanine transaminase （ALT），aspartate transaminase （AST），total bilirubin （TBil），creatinine （Cr），blood urea nitrogen （BUN），acute gastrointestinal injury （AGI） grade，gastrointestinal dysfunction score （GDS），serum intestinal fatty acid-binding protein （iFABP）， citrulline （CR），platelet （PLT），prothrombin time（PT），activated partial thromboplastin time （APTT），fibrinogen （Fib），international normalized ratio （INR），and D-dimer （D-D）. ResultsThere was no significant difference between the two groups regarding 28-day all-cause mortality. After the intervention，SOFA，WBC，PCT，and Cr were significantly decreased， and PLT was significantly increased in the control group （P<0.05）. SOFA，APACHE Ⅱ，NEU%，CRP，PCT，ALT，AST，Cr，BUN，AGI grade，GDS，and serum iFABP and CR were significantly improved in the observation group （P<0.05）. After the intervention，APACHE Ⅱ，PCT，AGI grade，GDS，and serum iFABP in the observation group were significantly lower than those in the control group ，while CR and PLT were higher （P<0.05，P<0.01）. There were significant differences regarding the gap of SOFA，APACHE Ⅱ，AST，TBil，AGI grade，GDS，iFABP，CR， and PLT between the two groups （P<0.05，P<0.01）. There were slight differences regarding PT，APTT，Fib，INR，and D-D between the two groups，which were in the clinical normal range. ConclusionOn the basis of Western medicine， DCH helped to reduce sepsis severity and improved multiple organ dysfunction with high clinical efficacy and safety， but further research on its impact on the prognosis of patients with sepsis is still required.

ObjectiveTo explore the potential mechanism of Xiezhuo Jiedu prescription in regulating autophagy in the treatment of ulcerative colitis （UC） by bioinformatics and animal experiments. MethodsThe differentially expressed genes （DEGs） in the colonic mucosal tissue of UC patients was obtained from the Gene Expression Omnibus （GEO）， and those overlapped with autophagy genes were obtained as the differentially expressed autophagy-related genes （DEARGs）. DEARGs were imported into Metascape and STRING， respectively， for gene ontology/Kyoto Encyclopedia of Genes and Genomics （GO/KEGG） enrichment analysis and protein-protein interaction （PPI） analysis. Finally， 15 key DEARGs were obtained. The core DEARGs were obtained by least absolute shrinkage and selection operator （LASSO） regression and receiver operating characteristic curve （ROC） analysis. The CIBERSORT deconvolution algorithm was used to analyze the immunoinfiltration of UC patients and the correlations between core DEARGs and immune cells. C57BL/6J mice were assigned into a normal group and a modeling group. The mouse model of UC was established by free drinking of 2.5% dextran sulfate sodium. The modeled mice were assigned into low-， medium-， and high-dose Xiezhuo Jiedu prescription and mesalazine groups according to the random number table method and administrated with corresponding agents by gavage for 7 days. The colonic mucosal morphology was observed by hematoxylin-eosin staining. The protein and mRNA levels of cysteinyl aspartate-specific proteinase 1 （Caspase-1）， cathepsin B （CTSB）， C-C motif chemokine-2 （CCL2）， CXC motif receptor 4 （CXCR4）， and hypoxia-inducing factor-1α （HIF-1α） in the colon tissue were determined by Western blot and real-time fluorescence quantitative polymerase chain reaction， respectively. ResultsThe dataset GSE87466 was screened from GEO and interlaced with autophagy genes. After PPI analysis， LASSO regression， and ROC analysis， the core DEARGs （Caspase-1， CCL2， CTSB， and CXCR4） were obtained. The results of immunoinfiltration analysis showed that the counts of NK cells， M0 macrophages， M1 macrophages， and dendritic cells in the colonic mucosal tissue of UC patients had significant differences， and core DEARGs had significant correlations with these immune cells. This result， combined with the prediction results of network pharmacology， suggested that the HIF-1α signaling pathway may play a key role in the regulation of UC by Xiezhuo Jiedu prescription. The animal experiments showed that Xiezhuo Jiedu prescription significantly alleviated colonic mucosal inflammation in UC mice. Compared with the normal group， the model group showed up-regulated protein and mRNA levels of caspase-1， CCL2， CTSB， CXCR4， and HIF-1α， which were down-regulated after treatment with Xiezhuo Jiedu prescription or mesalazine. ConclusionCaspase-1， CCL2， CTSB， and CXCR4 are autophagy genes that are closely related to the onset of UC. Xiezhuo Jiedu prescription can down-regulate the expression of core autophagy genes to alleviate the inflammation in the colonic mucosa of mice.

BACKGROUND:Cervical disc herniation can cause pain in the neck and shoulder area,as well as radiating pain in the upper limbs.The incidence rate is increasing year by year and tends to affect younger individuals.Fully understanding the biomechanical characteristics of the cervical spine in adolescents is of great significance for preventing and delaying the onset of cervical disc herniation in this age group. OBJECTIVE:To reconstruct cervical spine models for both healthy adolescents and adolescent patients with cervical disc herniation utilizing finite element analysis techniques,to analyze the motion range of the C1-T1 cervical vertebrae as well as the biomechanical characteristics of the annulus fibrosus,nucleus pulposus,endplates,and the cartilage of the small joints. METHODS:A normal adolescent's cervical spine and an adolescent patient with cervical disc herniation were selected in this study.The continuous scan cervical spine CT raw image data were imported into Mimics 21.0 in DICOM format.The C1-T1 vertebrae were reconstructed separately.Subsequently,the established models were imported into the 3-Matic software for disc reconstruction.The perfected models were then imported into Hypermesh software for meshing of the vertebrae,nucleus pulposus,annulus fibrosus,and ligaments,creating valid geometric models.After assigning material properties,the final models were imported into ABAQUS software to observe the joint motion range of the C1-C7 cervical vertebrae segments under different conditions,and to analyze the biomechanical characteristics of the annulus fibrosus,nucleus pulposus,endplates,and small joint cartilage of each cervical spine segment. RESULTS AND CONCLUSION:(1)In six different conditions,the joint motion range of the C1 vertebra in the cervical spine models of both normal adolescent and adolescent patient with cervical disc herniation was higher than that of the other vertebrae.Additionally,the joint motion range of each cervical spine segment in normal adolescent was greater than that in adolescent patient with cervical disc herniation.(2)In the cervical spine model of normal adolescent,the maximum stress values in the annulus fibrosus and nucleus pulposus were found on the left side during C2-3 flexion conditions(0.43 MPa and 0.17 MPa,respectively).In the cervical spine model of adolescent patient with cervical disc herniation,the maximum stress values were found on the left side during C7-T1 flexion conditions(0.54 MPa and 0.18 MPa,respectively).(3)In the cervical spine model of normal adolescent,the maximum stress value on the endplate was found on the left side of the upper endplate of C3 during flexion conditions(1.46 MPa).In the model of adolescent patient with cervical disc herniation,the maximum stress value on the endplate was found on the left side of the lower endplate of C7 during flexion conditions(1.32 MPa).(4)In the cervical spine model of normal adolescent,the maximum stress value in the small joint cartilage was found in the C2-3 left rotation conditions(0.98 MPa).In adolescent patient with cervical disc herniation,the stress in the small joint cartilage significantly increased under different conditions,especially in C1-2,with the maximum stress found during left flexion(3.50 MPa).(5)It is concluded that compared to normal adolescent,adolescent patient with cervical disc herniation exhibits altered cervical curvature and a decrease in overall joint motion range in the cervical spine.In adolescent with cervical disc herniation,there is a significant increase in stress on the annulus fibrosus,nucleus pulposus,and endplates in the C7-T1 segment.The stress on the left articular cartilage of the C1-2 is notable.Abnormal cervical curvature may be the primary factor causing these stress changes.

Objective: To retrospectively compare the safety and efficacy of ultrasound-guided radiofrequency ablation (RFA) with parotidectomy for superficial pleomorphic adenoma (PA). Materials and Methods: From March 2022 to October 2023, 88 patients diagnosed with superficial parotid PA underwent either RFA (n = 12; mean age, 47.1 years) or parotidectomy (n = 76; mean age, 47.8 years). Patients in the RFA group were matched to those in the surgery group in a 1:1 ratio using propensity scores based on age, sex, tumor volume, diameter, location, and comorbidities. Ultrasound characteristics, cosmetic scores (0–4), numerical rating scale scores (0–10), and complications were assessed before the procedures and at 1-, 3-, and 6-month follow-ups. Outcomes were compared between baseline and follow-up in the RFA group and between the RFA and surgery groups. Results: In the RFA group, significant reductions in tumor volume were observed between baseline (median, 2.02 cm 3 ) and the 1-month follow-up (median, 1.21 cm 3 ; P = 0.015), between the 1-month and 3-month follow-ups (median, 0.53 cm 3 ; P= 0.002), and between the 3- and 6-month follow-ups (median, 0.23 cm 3 ; P = 0.003). The volume reduction ratios at 1, 3, and 6 months were 39.7%, 79.9%, and 88.0%, respectively. The cosmetic score was significantly lower at 3- and 6-month followup compared to baseline (median 1 and 1 vs. 4, P = 0.04). The numerical rating scale scores did not differ significantly from baseline throughout follow-up. In the propensity score-matched analysis (12 patients per group), RFA was associated with a shorter median procedure time (61.5 vs. 253.3 minutes; P < 0.001), shorter hospital stay (0 vs. 4 days; P < 0.001), and lower cost (1859.9 vs. 3512.4 USD; P < 0.001) than parotidectomy, with no significant difference in overall complication rates (33.3% [4/12] vs. 41.7% [5/12]; P = 1.000). Conclusion RFA may be a safe and effective alternative to surgery for superficial parotid PA, offering a shorter median procedure time, shorter hospital stay, and lower costs.

OBJECTIVE To evaluate the efficacy， safety and cost-effectiveness of serplulimab as a first-line treatment of small- cell lung cancer （SCLC）， and provide an evidence-based basis for drug selection in hospitals. METHODS Rapid health technology assessment was adopted； PubMed， Cochrane Library， Embase， CNKI， Wanfang， VIP and official websites of domestic and international health technology assessment agencies were systematically searched from the inception to Oct. 2024. Two reviewers independently screened the literature， assessed the quality of included studies and carried out the qualitative analysis according to the inclusion and exclusion criteria. RESULTS A total of 13 systematic reviews/meta-analyses and 9 economic studies were included， and the literature quality was generally good. In terms of effectiveness， compared with chemotherapy alone， serplulimab combined with chemotherapy significantly improved progression-free survival， overall survival， and objective response rate in patients with SCLC. In terms of safety， serplulimab combined with chemotherapy showed no significant difference in the incidence of ≥3 grade adverse events compared with chemotherapy alone in the treatment of SCLC， indicating a good safety profile； compared with combination therapies involving other immunosuppressive agents， the incidence rate of adverse events was also lower. In terms of cost-effectiveness， compared with chemotherapy alone， serplulimab combined with chemotherapy is not cost- effective， which may be related to the high price of serplulimab. CONCLUSIONS Serplulimab is effective and safe in the treatment of SCLC， but has no obvious advantage in terms of cost-effectiveness.

The analysis presented here is based on the blood components of Guanxin Qiwei tablets, the key anti-atherosclerosis pathway of Guanxin Qiwei tablets was screened by network pharmacology, and the anti-atherosclerosis mechanism of Guanxin Qiwei tablets was clarified and verified by cell experiments. HPLC-Q-Exactive-MS/MS technique was used to analyze the components of Guanxin Qiwei tablets into blood, to determine the precise mass charge ratio of the compounds, and to conduct a comprehensive analysis of the components by using secondary mass spectrometry fragments and literature comparison. Finally, a total of 42 components of Guanxin Qiwei tablets into blood were identified. To better understand the interactions, we employed the Swiss Target Prediction database to predict the associated targets. Atherosclerosis (AS) disease targets were searched in disease databases Genecard, OMIM and Disgent, and 181 intersection targets of disease targets and component targets were obtained by Venny 2.1.0 software. Protein interactions were analyzed by String database. The 32 core targets were selected by Cytscape software. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed in DAVID database. It was found that the anti-atherosclerosis pathways of Guanxin Qiwei tablets mainly include lipid metabolism and atherosclerosis and AGE-RAGE signaling pathway in diabetic complications and other signal pathways. The core targets and the core compounds were interlinked, and it was found that cryptotanshinone and tanshinone ⅡA in Guanxin Qiwei tablets were well bound to TNF, PPARγ, AKT1, PTG2 and other targets. The lipid metabolism and atherosclerotic pathway was verified using human hl-7702 hepatocytes. This study preliminarily identified the potential pharmacodynamic components of Guanxin Qiwei tablets in the treatment of AS diseases and predicted their pathways of action, and verified the relationship between regulating lipid metabolism and atherosclerosis of Guanxin Qiwei tablets in vitro, providing a reference for the further study of the pharmacodynamic material basis and mechanism of action of this prescription. This experiment was approved by the Medical Ethics Committee of Inner Mongolia Medical University (No. YKD202401262).

Sleep， skin， and health are closely interconnected. Clinically， insomnia has a high incidence and is often accompanied by or secondary to skin aging. The two conditions exhibit "different diseases with the same syndrome"， significantly affecting the physical and mental health of the Chinese population. Preventing and treating skin aging by improving insomnia is an important strategy， with the principle of "treating different diseases with the same approach" serving as a crucial therapeutic guideline. However， effective clinical prevention and treatment methods for both conditions remain lacking. Traditional Chinese medicine （TCM） has a profound theoretical foundation and notable efficacy in the concurrent treatment of insomnia and skin aging， yet there are few reports on the etiology， pathogenesis， therapeutic principles， and treatment methods of their shared treatment， warranting further exploration. Based on holistic view and syndrome differentiation and treatment in TCM， this study systematically investigates the theoretical origins of the shared manifestations of insomnia and skin aging from multiple dimensions， including etiology， pathological location， pathogenesis， disease nature， and prevention and treatment strategies. As early as Huangdi's Internal Classic （Huangdi Neijing）， it was recognized that mental clarity during the day， sound sleep at night， and firm， healthy skin are key indicators of external health， whereas daytime lethargy， poor sleep quality， and dry， withered skin are prominent signs of aging. Maintaining mental clarity during the day and restful sleep at night is essential for skin integrity and healthy aging. Later medical scholars proposed that the common etiology of insomnia and skin aging lies in "internal-external interactions"， with the pathological location involving "the five organ systems". The primary pathogenesis includes "deficiency， fire， stagnation， phlegm， and blood stasis"， while the disease nature is often characterized by "a combination of deficiency and excess". Treatment should be guided by syndrome differentiation， following the principle of balancing Yin and Yang. This theoretical exploration enriches and advances TCM understanding of disease onset and prevention， providing theoretical guidance for the clinical prevention and treatment of insomnia-associated skin aging and contributing to the realization of the "Healthy China" initiative.