OBJECTIVE To systematically compare mature experiences of comprehensive drug value assessment in typical countries/regions and to provide decision-making references for China to establish a scientific and standardized comprehensive drug value assessment system for medical-insured drugs. METHODS The literature analysis was used to systematically review drug value assessment frameworks in 11 representative countries/regions， namely the UK， Canada， Italy， Australia， Germany， France， South Korea， Japan， the United States， as well as Taiwan （China） and Hong Kong （China）. Comparisons were made across three dimensions： assessment entities， value dimension， and application of results. RESULTS &CONCLUSIONS In most countries/regions， independent technical assessment institutions have been established as part of the drug value evaluation system， with the involvement of multiple stakeholders （e.g.， the UK， Canada）. The mainstream drug value assessment frameworks have generally transcended the traditional core dimensions of safety， efficacy， and cost-effectiveness， exhibiting two major trends： the continuous expansion of assessment dimensions and stricter evidence requirements. Assessment outcomes are closely integrated with payment policies， ranging from providing technical advice for decision-making （e.g.， Italy， France） to directly determining reimbursement eligibility （e.g.， the UK， Germany）. The following recommendations are proposed for China： first， establish an evaluation mechanism featuring multi-stakeholder participation and separation of evaluation from decision-making. Second， develop a comprehensive evaluation framework integrating clinical， economic， patient， and societal value， emphasizing quantitative indicator exploration and real-world evidence application. Third， promote direct linkage between value-based tiering outcomes and medical insurance reimbursement decisions or access negotiations to balance patient benefits， fund sustainability， and industrial innovation.

This paper proposes a two-stage method integrating visual foundation models （VFM） and diffusion models. The segment anything model （SAM） as VFM is combined with the SegRefiner diffusion model to construct the SAM-SegRefiner framework for automated segmentation of edema， inflammation， and thrombus regions in histopathological images of hemorrhoidal tissue， providing a reproducible technical tool for the objective quantification of pathological morphology and its application in traditional Chinese medicine （TCM） syndrome research. Trained and validated on multi-center retrospective data， the SAM-SegRefiner model achieved an average pixel accuracy of 95.32% and a mean intersection over union （mIoU） of 66.81% on an independent test set， significantly outperfor-ming comparative models such as U-Net， MixU-Net， and SAM-Med2D， and also demonstrating robust cross-center generalization capability. Furthermore， by correlating the quantitatively segmented results from the model with the patients' TCM syndrome types， the potential associations between pathomorphological features and TCM syndrome differentiation have been explored. The analysis revealed no statistically significant differences in the degree of inflammatory infiltration and thrombus formation among different syndrome types， suggesting a complex relationship between local pathological changes and systemic syndrome manifestations.

Immune-stimulating antibody drug conjugate (ISAC) can not only effectively solve the defects of stimulator of interferon genes (STING) agonists by coupling antibodies with STING agonists through the targeting of antibodies, but also play a synergistic role with antibodies to further improve the efficacy of STING agonists. This review first provides a concise overview of the current research landscape of ISACs and STING agonists, systematically elaborates on evolving trends in STING agonist development, and subsequently summarizes the mechanistic advances in STING ISAC research. Special emphasis is placed on representative STING ISAC candidates in preclinical/clinical development. Finally, the future directions of STING ISACs are critically discussed with perspectives and recommendations, aiming to provide theoretical insights and practical guidance for future investigations.

ObjectiveTo explore the mechanism of action of Paeoniae Radix Rubra and Aconiti Lateralis Radix Praeparata （CSFZ） in the treatment of acute-on-chronic liver failure （ACLF） through network pharmacology， molecular docking， and animal experiments. MethodsNetwork pharmacology was used to identify potential targets and related signaling pathways for the treatment of ACLF with CSFZ. Molecular docking was used to examine the binding activity of the core components with corresponding key targets. An ACLF rat model was established by subcutaneous and tail vein injections of bovine serum albumin combined with lipopolysaccharide （LPS） + D-galactosamine （D-GalN） intraperitoneal injection. A normal control group （NC）， a model group， a CSFZ group （CSFZ， 5.85 g·kg^-1）， and a hepatocyte growth-promoting granule group （HGFG， 4.05 g·kg^-1） were set up in this study. Pathological changes in rat liver tissue were observed using hematoxylin and eosin （HE） and Masson staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression levels of interleukin-6 （IL-6）， B-cell lymphoma-2 （Bcl-2）， Caspase-3， and albumin （ALB）. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to measure the mRNA and protein expression levels of phosphoinositide 3-kinase （PI3K）， protein kinase B （Akt）， phosphorylated PI3K （p-PI3K）， and phosphorylated Akt （p-Akt）. ResultsNetwork pharmacology screening identified 49 active ingredients of CSFZ， 103 action targets， and 3 317 targets related to ACLF. Among these， 74 targets overlapped with CSFZ drug targets. Key nodes in the protein-protein interaction （PPI） network included Akt1， tumor necrosis factor （TNF）， IL-6， Bcl-2， and Caspase-3. Gene Ontology （GO） functional analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis identified multiple signaling pathways， with the PI3K/Akt signaling pathway being the most frequent. Molecular docking showed that the core components of the drug exhibited good binding activity with the corresponding key targets. Animal experiments confirmed that CSFZ significantly improved liver tissue pathological damage in ACLF rats， reduced the release of inflammatory factors and liver cell apoptosis， and upregulated the expression levels of the PI3K/Akt signaling pathway. ConclusionThrough network pharmacology， molecular docking， and in vivo experiments， this study confirms the effect of CSFZ in reducing liver cell inflammatory damage and inhibiting liver cell apoptosis. The specific mechanism may be related to its involvement in regulating the PI3K/Akt signaling pathway.

ObjectiveTo explore the mechanism of Shouhui Tongbian capsules in treating constipation based on the research foundation of its active components combined with network pharmacology and animal experiments. MethodsThe drug components were imported into SwissTargetPrediction to predict the targets of Shouhui Tongbian capsules， and constipation-related targets were collected from disease databases. A protein-protein interaction （PPI） network was constructed for the common targets shared by Shouhui Tongbian capsules and constipation to screen key targets， which was followed by gene ontology （GO） function and Kyoto encyclopedia of genes and genomes （KEGG） pathway enrichment analyses. A "bioactive component-target-pathway" network was constructed， and the core components of Shouhui Tongbian capsules in treating constipation were screened based on the topological parameters of this network. Molecular docking was employed to predict the binding affinity of core components to key targets. A mouse model of constipation was constructed to screen the key pathways and targets of the drug intervention in constipation. ResultsThe PPI network revealed six key constipation-related targets： protein kinase B （Akt1）， B-cell lymphoma-2 （Bcl-2）， glycogen synthase kinase-3β （GSK-3β）， cyclooxygenase-2 （PTGS2）， estrogen receptor 1 （ESR1）， and epidermal growth factor receptor （EGFR）. The KEGG pathway analysis showed that the phosphatidylinositol 3-kinase （PI3K）/Akt signaling pathway was the most enriched. The topological parameter analysis of the "bioactive component-target-pathway" network screened out the top 10 core components： auranetin， isosinensetin， naringin， diosmetin， quercetin， apigenin， luteolin， hesperidin， isorhapontigenin， and chrysophanol. Molecular docking results showed that the 10 core components had strong binding affinity with the 6 key targets. Animal experiments showed that after intervention with different doses of Shouhui Tongbian capsules， the time to the first black stool excretion was reduced and the fecal water content and small intestine charcoal propulsion rate of mice were improved. After treatment with Shouhui Tongbian capsules， the colonic mucosal injury and glandular arrangement were alleviated， and the muscle layer thickness was increased. Western blot results showed that Shouhui Tongbian capsules recovered the expression of apoptosis-related molecules mediated by the PI3K/Akt pathway in the colonic tissue of constipated mice. Terminal-deoxynucleotidyl transferase-mediated nick end labeling （TUNEL） results showed that the cell apoptosis rate of the colon significantly reduced after intervention with Shouhui Tongbian capsules. ConclusionThe results of network pharmacology and animal experiments confirmed that Shouhui Tongbian capsules can treat constipation through multiple targets and pathways. The capsules can effectively intervene in loperamide-induced constipation in mice by regulating the constipation indicators and reducing cell apoptosis in the colon tissue via activating the PI3K/Akt signaling pathway.

ObjectiveTo investigate the effect and therapeutic role of quercetin on ferroptosis in lipopolysaccharide （LPS）-induced acute kidney injury （AKI） rats based on the Kelch-like epichlorohydrin-related protein-1 （Keap1）/nuclear factor erythroid-2-related factor 2 （Nrf2）/antioxidant response element （ARE） pathway. MethodsSixty male SD rats were randomly divided into normal group， model group， quercetin high-dose （100 mg·kg^-1） and low-dose （10 mg·kg^-1） groups， ferroptosis inhibitor Ferrostatin 1 （FER1） group （5 mg·kg^-1）， and quercetin high-dose + Nrf2 inhibitor group （ML385， 30 mg·kg^-1）. Except for the normal group， the AKI rat model was established in each group by intraperitoneal injection of LPS （10 mg·kg^-1）. Following successful modeling， each treatment group received the corresponding dose of drug intervention， while the normal and model groups were administered an equal volume of normal saline. The intervention lasted for 3 weeks. Serum creatinine （SCr） and blood urea nitrogen （BUN） levels were measured biochemically to assess renal function. Serum tumor necrosis factor-α （TNF-α） and interleukin （IL）-1β and IL-6 levels were detected by enzyme-linked immunosorbent assay （ELISA）. The levels of Fe²⁺， malondialdehyde （MDA）， superoxide dismutase （SOD）， and glutathione （GSH） in renal tissue were detected. Hematoxylin-eosin （HE）， Masson， and periodic acid-Schiff （PAS） staining were employed to observe pathological morphological changes in renal tissue. Mitochondrial morphological changes were observed using transmission electron microscopy. Reactive oxygen species （ROS） levels in renal tissue were detected by immunofluorescence （IF）. The protein and mRNA expression levels of Keap1， Nrf2， heme oxygenase-1 （HO-1）， glutathione peroxidase 4 （GPX4）， transferrin receptor （TFR1）， and kidney injury molecule-1 （KIM-1） were assessed by immunohistochemistry （IHC） and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the normal group， the model group exhibited significantly elevated serum levels of SCr， BUN， TNF-α， IL-1β， IL-6， Fe²⁺ and MDA in renal tissue， and significantly reduced SOD and GSH levels （P<0.01）. Pathological injury in renal tissue was severe， with evident mitochondrial damage characteristic of ferroptosis and a reduced mitochondrial count. ROS levels in renal tissue were significantly increased. The protein and mRNA expression levels of Keap1， TFR1， and KIM-1 in renal tissue were significantly elevated， while those of Nrf2， HO-1， and GPX4 were significantly decreased （P<0.01）. Compared with the model group， serum levels of SCr， BUN， TNF-α， IL-1β， IL-6， Fe²⁺ and MDA in renal tissue in the quercetin dosage groups and FER1 group showed varying degrees of reduction， while SOD and GSH levels were significantly increased （P<0.05）. Pathological injury in renal tissue was markedly alleviated， mitochondrial damage improved， and mitochondrial counts increased. ROS levels in renal tissue were significantly reduced. The protein and mRNA levels of Keap1， TFR1， and KIM-1 in renal tissue were significantly decreased， while those of Nrf2， HO-1， and GPX4 were significantly increased， with the most notable improvement in the high-dose quercetin group （P<0.05）. In comparison to the high-dose quercetin group， the ML385 group significantly weakened the protective effect of quercetin on AKI rats （P<0.05）. ConclusionQuercetin effectively inhibits ferroptosis， improves renal tissue injury， and repairs renal function in AKI rats， and its mechanism may be related to the activation of the Keap1/Nrf2/ARE pathway.

Objective: To analyze the change trends in the body shape indicators and proportions of students in Harbin from 2010 to 2024, and to investigate ergonomic compatibility of functional dimensions of school desks and chairs with current student shape indicators, so as to provide a reference for revising furniture standards of desks and chairs. Methods: Between September and November of both 2010 and 2024, a combination of convenience sampling and stratified cluster random sampling was conducted across three districts in Harbin, yielding samples of 6 590 and 6 252 students, respectively. Anthropometric shape indicators cluding height, sitting height, crus length, and thigh length-and their proportional changes were compared over the 15-year period. The 2024 data were compared with current standard functional dimensions of school furniture. The statistical analysis incorporated t-test and Mann-Whitney U- test. Results: From 2010 to 2024, average height increased by 1.8 cm for boys and 1.5 cm for girls; sitting height increased by 1.5 cm for both genders; crus length increased by 0.3 cm for boys and 0.4 cm for girls; and thigh length increased by 0.5 cm for both genders. The ratios of sitting height to height, and sitting height to leg length increased by less than 0.1 . The difference between desk chair height and 1/3 sitting height ranged from 0.4-0.8 cm. Among students matched with size 0 desks and chairs, 22.0% had a desk to chair height difference less than 0, indicating that the desk to chair height difference might be insufficient for taller students. The differences between seat height and fibular height ranged from -1.4 to 1.1 cm; and the differences between seat depth and buttock popliteal length ranged from -9.8 to 3.4 cm. Among obese students, the differences between seat width and 1/2 hip circumference ranged from -20.5 to -8.7 cm, while it ranged from -12.2 to -3.8 cm among non obese students. Conclusion Current furniture standards basically satisfy hygienic requirements; however, in the case of exceptionally tall and obese students, ergonomic accommodations such as adaptive seating allocation or personalized adjustments are recommended to meet hygienic requirements.

ObjectiveTo find out whether there is any difference in the monitoring results of mosq-ovitraps placed in different orientations in multi-storey residential areas, so as to provide a scientific basis for routine and emergency monitoring of Aedes albopictus with mosq-ovitraps in residential areas. MethodsFrom July 6th to October 26th 2023, one mosquito ovitrap was set up in each of the 4 orientations of east, south, west and north around the buildings in a multi-storey residential area in Jinhui Town, Fengxian District, Shanghai. Data was collected and recorded 72 hours after placement. The chi-square test was used to compare the mosquito ovitrap indices (MOIs) of two independent samples, and the Kruskal⁃Wallis H test was used to compare the MOIs of multiple independent samples. ResultsAfter 16 weeks of surveillance, 997 mosquito ovitraps were recovered, of which 211 were positive, with the mosquito ovitrap index (MOI) of 21.16% and the Aedes albopictus density index of 1.03 mosquitoes·ovitrap^-1. The MOIs were higher in September (24.22%) and October (23.96%), and the MOIs in the west, south and north within the two months were all above 20.00%. From July to October, the MOIs in the east, west, south and north were 20.70%, 22.20%, 25.50% and 16.20%, respectively, and the difference in MOIs among the 4 orientations was not statistically significant (χ²=6.647, P=0.084). Stratified analysis by month showed that in August, the south side of the multi-storey residential areas had the highest MOI (31.30%), the north side had the lowest MOI (1.30%), and there was a statistically significant difference in MOI in the east, west, south and north (χ²=25.986, P<0.001). In October, the MOI in the west was the highest (33.30%) and the MOI in the east was the lowest (6.30%), the difference in MOIs of the 4 orientations was statistically significant (χ²=12.007, P=0.007). The MOIs in the south side of the building in the outskirts of the residential area from the 1st week in July to the 4th week in October was lower (19.20%) than that in the south side of the inner building (31.70%), and the difference in MOI was statistically significant (χ²=5.118, P=0.024). ConclusionThe study of MOI in different orientations in a multi-storey residential area is a preliminary exploration based on field work, and the results show that there is a difference in MOIs in different orientations during the peak breeding period of mosquitoes. Further indicators such as temperature, humidity and wind speed in different orientations can be collected to explore the influencing factors of MOIs.

Objective: To evaluate the efficacy of the left spermatic vein transposition to the great saphenous vein in treating left varicocele (VC) secondary to nutcracker syndrome (NCS). Methods: Clinical data of 8 patients treated during Feb.2020 and Feb.2023 in our hospital were retrospectively analyzed.A meticulous preoperative evaluation of the vascular status of the spermatic vein and the great saphenous vein was performed using color Doppler ultrasound.A spermatic vein-great saphenous vein shunt surgery was performed in patients who were strictly selected.The clinical symptoms and hemodynamics of renal vein were compared before and after operation. Results: The median age of patients was 23.5(18-33) years.There was a notable reduction in post-exercise scrotal and lower back pain in all patients，and the score of scrotal pain decreased to 0 in 7 patients. The median quantification of urinary protein was 352.8(54.4-687.3) mg prior to surgical intervention，which significantly diminished to 125.5(25.9-255.1) mg 6 months after operation.Notably，3 cases of preoperative positive urine occult blood tests were undetectable in the subsequent postoperative assessments.The median peak blood flow velocity at the site of stenosis in the left renal vein measured at 74.4(48.7-117.6) cm/s preoperatively，subsequently reduced to 45.1(25.5-61.2) cm/s postoperatively.During the 6-month follow-up，no recurrence of varicocele，vascular anastomotic stenosis or thrombosis were observed. Conclusion: Our research indicates that spermatic vein to great saphenous vein bypass is safe and feasible in the treatment of left varicocele secondary to nutcracker syndrome for strictly selected patients，which can effectively alleviate renal vein congestion without significant complications.

Objective: To explore the role and mechanism of epiregulin (EREG) in clear cell renal cell carcinoma (ccRCC)，and to find biomarkers and therapeutic targets for ccRCC. Methods: Based on the data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases，the correlation between the expression level of EREG in ccRCC tissues and the clinical staging and survival of ccRCC patients was analyzed. The samples of 6 ccRCC cases treated in the Second Affiliated Hospital of the Air Force Medical University were collected. The expression of EREG was confirmed with immunohistochemistry and quantitative real-time polymerase chain reaction (q-PCR). The effects of EREG overexpression on the proliferation，cell cycle and apoptosis of ACHN cells were verified with CCK-8 and flow cytometry. Finally，the expressions of EREG，epidermal growth factor receptor (EGFR) and the downstream pathway proteins were detected with Western blotting. Results: Based on the databases，it was found that the expression of EREG in ccRCC samples was higher than that in adjacent tissues，and there was a positive correlation with the clinical stage. Survival analysis showed that high expression of EREG was a risk factor affecting the prognosis. The results of immunohistochemical staining and qPCR revealed that EREG was highly expressed in ccRCC. Flow cytometry showed that EREG overexpression promoted the proliferation of ACHN cells，enhanced cell cycle，and inhibited apoptosis. In addition，Western blotting suggested that EREG promoted the expressions of EREG，EGFR and the downstream proteins. Conclusion: The expression of EREG is associated with the prognosis of ccRCC patients. In vitro cell experiments have shown that it can promote the proliferation of ccRCC cells and inhibit their apoptosis，thereby leading to the progression of ccRCC. It can serve as a potential biomarker for prognosis prediction and a drug development target for ccRCC patients.