OBJECTIVE To introduce the development of an intelligent prescription review decision-support system for anti-tumor drugs and assess its clinical application outcomes. METHODS Relevant data sources， including national and local pharmaceutical administration policies， clinical practice guidelines/consensus， hospital information systems data， and genetic testing results， were integrated. Adhering to the principles of structure， standardization and dynamic updating， a knowledge base covering chemotherapeutic， targeted and immunotherapeutic agents was constructed using a dual-dimensional modeling approach that combined “drug attributes” and “clinical contexts”. This knowledge base was then embedded into the hospital’s electronic medical order system to establish the prescription review decision-support system. The application and performance of the system were evaluated at Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. RESULTS A knowledge base containing 18 318 prescription review rules for anti-tumor drugs was constructed， and a closed-loop prescription review system was successfully established， encompassing pre-prescription real-time intervention， in-process interactive review， and post-prescription evaluation and analysis. From 2021 to 2024， the system generated a total of 57 879 alerts for prescriptions of five typical categories of anti-tumor drugs. For platinum-containing prescriptions， 22 577 alerts were generated， with Cisplatin for injection （lyophilized） being the most frequently alerted drug （13 445 alerts）， and “ototoxicity risk due to combined use” alerts remained high （7 682 alerts）. For methotrexate-containing prescriptions， 3 721 alerts were recorded， primarily related to “precaution-related issues” （76.4%， 2 843/3 721）. For doxorubicin-containing prescriptions， 17 301 alerts were triggered， primarily related to “dosage and administration” （14 315 alerts）. For human epidermal growth factor receptor 2-targeted agents-containing prescriptions， 1 007 alerts were issued， mostly related to “reimbursement restrictions” （956 alerts）. For programmed death-1/programmed death-ligand 1 inhibitors-containing prescriptions， the alerts increased year by year， totaling 13 273 alerts， primarily related to “inappropriate indication” （9 118 alerts）. Over the 4 years， the physician response rates to system alerts were 21.4%， 27.1%， 33.5% and 51.6%， respectively. CONCLUSIONS An intelligent decision-support system for anti-tumor drug prescription review， encompassing a closed-loop process of “real-time pre-event intervention， interactive in-event prescription review， post-event evaluation and analysis”， has been successfully constructed and implemented throughout the entire workflow. There is a discernible trend in this hospital， where the focus on monitoring anti-tumor drugs is shifting towards immunotherapy drugs. Additionally， the acceptance rate of physicians regarding prescription review opinions has been steadily increasing year by year.

OBJECTIVE To investigate the improvement effects and potential mechanisms of Sangbaipi decoction （SBP） on mice with second-hand smoke-induced pulmonary fibrosis （PF）. METHODS Using network pharmacology methods， the common targets between the active components of SBP and PF-specific targets were screened， the protein-protein interaction network was constructed， the pathway enrichment analysis was performed using the Kyoto Encyclopedia of Genes and Genomes， and the molecular docking was conducted. Based on these results， the male Kunming mice were divided into a normal control group， a model control group， an SBP group （1.08 g/kg， calculated by crude drugs）， and a pirfenidone group （positive control， 90 mg/kg）， with eight mice in each group. Except for the normal control group， all other groups were exposed to second-hand smoke via the static respiratory tract smoking method （30 min of smoking twice daily for 20 consecutive days） to establish a mouse model of PF induced by second-hand smoke. Each drug group was administered the corresponding drug solution via gavage 0.5 h after the second daily smoke exposure； the normal control and model control groups were simultaneously administered an equal volume of water via gavage， once daily for 20 consecutive days. Twenty-four hours after the final administration， pathological changes in lung tissue were observed， and the levels of pro-inflammatory factors， injury markers， and the expression of proteins in related signaling pathways in lung tissue were detected. RESULTS A total of 2 448 common targets were identified， with core targets including protein kinase B1 （AKT1）， tumor necrosis factor-α （TNF-α）， and interleukin-6 （IL-6）， which were enriched in signaling pathways such as phosphoinositide 3-kinase （PI3K）/AKT. The bin ding energies of AKT1， PI3K， TNF-α， and IL-6 to the active compound chaksine were －11.0， －7.7， －9.0， and －9.4 kcal/mol， respectively. Compared with the model control group， pathological changes such as inflammatory cell infiltration and collagen deposition in lung tissue were alleviated in the administration groups. The expression of collagen Ⅲ in lung tissue was significantly downregulated， and the levels of IL-6， TNF-α， tissue inhibitor of metalloproteinase 1， and pulmonary surfactant-associated protein D， as well as the percentage of positive areas with pulmonary fibrosis and protein phosphorylation levels of PI3K and AKT， were all significantly downregulated or reduced （ P ＜0.05）. CONCLUSIONS The role of SBP in improving PF induced by second-hand smoke may be related to the regulation of multiple core targets， including AKT1， and the inhibition of the PI3K/AKT signaling pathway， thereby alleviating pulmonary inflammation and collagen deposition.

The recombinant human thyroid-stimulating hormone (rhTSH) can be used for differentiated thyroid cancer (DTC) preparation before ¹³¹I therapy, and follow-up. Since its approval by the American Food and Drug Administration (FDA) in 1998, rhTSH has been clinically used in European countries, the United States, and other countries for nearly 30 years. In April 2024, China’s first independently developed rhTSH agent was approved. Based on clinical experience and evidence from domestic and international studies, an expert consensus on the application of rhTSH has been developed following thorough consultations among experts. The consensus offers evidence-based recommendations to guide the appropriate use of rhTSH in clinical practice.

This paper discussed the differentiation and treatment of chemotherapy-induced nausea and vomiting （CINV） in traditional Chinese medicine， based on the theory of "yin qi descends， while all yang qi ascends” from Inner Canon of Yellow Emperor （《黄帝内经》）. The core pathogenesis of CINV is attributed to chemotherapy-induced injury to the middle jiao （焦）， resulting in the separation of yin and yang and loss of their mutual communication. Acute and explosive CINV is often characterized by "all yang qi ascends"， with stomach yang constraint transforming into fire， and qi counterflow leading to vomiting， which can be treated by unblocking stomach yang， draining fire and scattering the counterflow， with Huoxiang Zhengqi Powder （藿香正气散） and medicinals of clearing function. For delayed cases， which are often due to "yin qi descends"， and the accumulation of turbid yin obstructs and constrains the deficient yang， the treatment should focus on promoting qi flow to eliminate turbidity， unblocking and boosting yang qi， and Chengqi-series Formulas （承气类方） or Xiao Banxia Decoction （小半夏汤） can be considered. Refractory and anticipated cases usually involve stomach-kidney deficiency and zang-fu （脏腑） organs disharmony， making yin and yang difficult to restore balance， for which the treatment should focus on nourishing both the stomach and kidneys and harmonize the zang-fu organs， with formulas such as Fuzi Lizhong Decoction （附子理中汤） or Xiaoyao Powder （逍遥散） modified as appropriate.

Objective:To evaluate the effectiveness of yttrium aluminum garnet (Nd∶YAG) laser vitreolysis in the treatment of symptomatic vitreous opacity.Methods:An observational case series study was performed.Forty-four eyes of 44 patients diagnosed as physiological vitreous opacity in Shenzhen Eye Hospital from June 2021 to September 2022 and treated with Nd∶YAG laser vitreolysis were enrolled.Before treatment and 2 months after last treatment, best corrected visual acuity (BCVA) evaluated with standard logarithmic visual acuity chart, floater areas calculated through infrared fundus photography, and objective scattering index (OSI) obtained by the Optical Quality Analysis System (OQAS) were recorded.The occurrence of complications during the follow-up period was recorded.The differences in each indicator were compared, and a simple linear regression model was used to analyze the relationship between floater area and OSI.This study adhered to the Declaration of Helsinki and was approved by the Medical Ethics Committee of Shenzhen Eye Hospital (No.2021-6-3).Patients were informed of the study methods and purposes.Written informed consent was obtained from each subject.Results:There was no significant difference in BCVA before and after Nd∶YAG laser vitreolysis ( t=-0.478, P=0.635).The floater area before laser treatment was (3.043±1.942)mm 2, which was significantly larger than (1.074±0.735)mm 2 after laser treatment ( t=0.769, P<0.001).The OSI before laser treatment was 1.976±0.975, which was significantly greater than 1.560±0.796 after laser treatment ( t=0.730, P<0.001).The results of linear regression analysis showed that the OSI=1.45+ 0.16× floater area ( F=5.681, P=0.020).No patient had visual acuity loss or intraocular pressure increase and no traumatic cataract or retinal damage occurred. Conclusions:After laser treatment, the floater area decreased, the OSI decreased, and the visual quality of patients improved.The OSI from OQAS Ⅱ and floater area can be used as quantitative evaluation indicators to objectively evaluate the effectiveness of Nd∶YAG laser vitreolysis.

Recent data suggest that vascular endothelial growth factor receptor inhibitor (VEGFRi) can enhance the anti-tumor activity of the anti-programmed cell death-1 (anti-PD-1) antibody in colorectal cancer (CRC) with microsatellite stability (MSS). However, the comparison between this combination and standard third-line VEGFRi treatment is not performed, and reliable biomarkers are still lacking. We retrospectively enrolled MSS CRC patients receiving anti-PD-1 antibody plus VEGFRi (combination group, n=54) or VEGFRi alone (VEGFRi group, n=32), and their efficacy and safety were evaluated. We additionally examined the immune characteristics of the MSS CRC tumor microenvironment (TME) through single-cell and spatial transcriptomic data, and an MSS CRC immune cell-related signature (MCICRS) that can be used to predict the clinical outcomes of MSS CRC patients receiving immunotherapy was developed and validated in our in-house cohort. Compared with VEGFRi alone, the combination of anti-PD-1 antibody and VEGFRi exhibited a prolonged survival benefit (median progression-free survival: 4.4 vs. 2.0 months, P=0.0024; median overall survival: 10.2 vs. 5.2 months, P=0.0038) and a similar adverse event incidence. Through single-cell and spatial transcriptomic analysis, we determined ten MSS CRC-enriched immune cell types and their spatial distribution, including naive CD4⁺ T, regulatory CD4⁺ T, CD4⁺ Th17, exhausted CD8⁺ T, cytotoxic CD8⁺ T, proliferated CD8⁺ T, natural killer (NK) cells, plasma, and classical and intermediate monocytes. Based on a systemic meta-analysis and ten machine learning algorithms, we obtained MCICRS, an independent risk factor for the prognosis of MSS CRC patients. Further analyses demonstrated that the low-MCICRS group presented a higher immune cell infiltration and immune-related pathway activation, and hence a significant relation with the superior efficacy of pan-cancer immunotherapy. More importantly, the predictive value of MCICRS in MSS CRC patients receiving immunotherapy was also validated with an in-house cohort. Anti-PD-1 antibody combined with VEGFRi presented an improved clinical benefit in MSS CRC with manageable toxicity. MCICRS could serve as a robust and promising tool to predict clinical outcomes for individual MSS CRC patients receiving immunotherapy.
Humans ; Colorectal Neoplasms/drug therapy* ; Male ; Female ; Immunotherapy ; Middle Aged ; Aged ; Tumor Microenvironment/immunology* ; Retrospective Studies ; Microsatellite Instability ; Transcriptome ; Single-Cell Analysis ; Programmed Cell Death 1 Receptor/immunology* ; Gene Expression Profiling ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors*

Identification of disease-specific cell subtypes (DSCSs) has profound implications for understanding disease mechanisms, preoperative diagnosis, and precision therapy. However, achieving unified annotation of DSCSs in heterogeneous single-cell datasets remains a challenge. In this study, we developed the gPRINT algorithm (generalized approach for cell subtype identification with single cell's voicePRINT). Inspired by the principles of speech recognition in noisy environments, gPRINT transforms gene position and gene expression information into voiceprints based on ordered and clustered gene expression phenomena, obtaining unique "gene print" patterns for each cell. Then, we integrated neural networks to mitigate the impact of background noise on cell identity label mapping. We demonstrated the reproducibility of gPRINT across different donors, single-cell sequencing platforms, and disease subtypes, and its utility for automatic cell subtype annotation across datasets. Moreover, gPRINT achieved higher annotation accuracy of 98.37% when externally validated based on the same tissue, surpassing other algorithms. Furthermore, this approach has been applied to fibrosis-associated diseases in multiple tissues throughout the body, as well as to the annotation of fibroblast subtypes in a single tissue, tendon, where fibrosis is prevalent. We successfully achieved automatic prediction of tendinopathy-specific cell subtypes, key targets, and related drugs. In summary, gPRINT provides an automated and unified approach for identifying DSCSs across datasets, facilitating the elucidation of specific cell subtypes under different disease states and providing a powerful tool for exploring therapeutic targets in diseases.
Humans ; Algorithms ; Single-Cell Analysis ; Databases, Genetic ; Molecular Sequence Annotation

OBJECTIVE To compare the efficacy， safety， and cost-effectiveness of two different formulations of short-acting recombinant human growth hormone （rhGH） in the treatment of patients with short stature. METHODS Data from patients with short stature treated with short-acting rhGH at the Leshan People’s Hospital from August 2016 to June 2023 were collected. Patients were divided into powder formulation group and aqueous formulation group based on the rhGH formulation used. The changes in growth-related efficacy indicators and the occurrence of adverse drug reactions were compared between two groups after 12 months of treatment； cost-effectiveness analysis and sensitivity analysis were used to compare the cost per unit of effect achieved； subgroup analysis was performed by dividing the patients into growth hormone deficiency （GHD） subgroup and idiopathic short stature （ISS） subgroup based on clinical diagnosis. RESULTS After 12 months of treatment， the height and the levels of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 in serum in aqueous formulation group and powder formulation group were significantly increased compared to before treatment （P＜0.001）， but there was no statistically significant difference in the changes of the above indicators between the two groups（P＞0.05）. The analysis results of GHD and ISS subgroups were consistent with the overall population. In the overall population， the cost-effectiveness ratio of powder formulation group （2 582 yuan/cm） was significantly better than that of aqueous formulation group （6 729 yuan/cm）， with a statistically significant difference （P＜0.001）， and the result was consistent in the GHD and ISS subgroups as well as in the sensitivity analysis. No serious adverse drug reactions occurred in either powder formulation or aqueous formulation group， and there was no statistically significant difference in the incidence of various adverse reactions between two groups （P＞0.05）. CONCLUSIONS Short-acting rhGH powder and aqueous formulations have equivalent efficacy and safety， but the powder formulation has greater economic advantages.

Objective This research was performed to identify rodent-borne pathogens in Hekou Port,Yunnan Province.Methods Rodents were captured using cages and dissected to collect their lungs,liver,spleen,and other viscera.Eight pathogens,including Yersinia pestis,Leptospira,Bartonella,and Anaplasmataceae,were identified using polymerase chain reaction amplification.Amplified pathogen sequences from positive samples were sequenced,and BLAST homology searches were conducted using GenBank to confirm pathogen identities.A phylogenetic tree of the identified pathogens was constructed using the neighbor joining method.Results The total of 31 rodents,identified as Rattus tanezumi,R.norvegicus,and Mus musculus,were captured.Among these,R.tanezumi was the dominant species,accounting for 64.52％of the total.Two pathogens,Leptospira interrogans and Neoehrlichia mikurensis,were detected,with positivity rates of 9.68％and 29.03％,respectively.No other pathogens were detected.The overall positivity rate for rodent-borne pathogens was 35.48％.Conclusions The single 16S rRNA gene fragment is insufficient for the molecular identification of all Neoehrlichia species.Accurate species identification should be based on a combined analysis of multiple genes.The prevalence of rodent-borne pathogens in Hekou Port indicates the necessity for enhanced surveillance of rodent-borne diseases and implementation of additional prevention and control measures in border ports.