OBJECTIVE To establish a closed-loop management system for the whole-process traceability of outpatient drugs based on internet of things （IoT） and blockchain technology， and evaluate its implementation effects. METHODS A closed-loop management system for the whole-process traceability of outpatient drugs covering the entire drug lifecycle was designed using drug traceability codes integrated with IoT and blockchain technology. System effectiveness was evaluated from three dimensions： work efficiency， medication management quality and data safety by comparing indicators such as the acceptance time of incoming drugs and the number of collected drug traceability codes before the system implementation （October to December 2024） and after the system implementation （January to March 2025）. RESULTS A closed-loop management system for the whole-process traceability of outpatient drugs， centered around the drug traceability code management system， was successfully established. The acceptance time for incoming drugs was shortened from （4.65±0.26） h before implementation to （0.34±0.08） h after implementation （P＜ 0.05）. The number of collected drug traceability codes increased from 419 018 to 1 236 522， and the coverage rate of traceability codes rose from 28.36% to 89.88% （P＜0.05）. The time pharmacists spent on drug expiry management per week decreased from （128.40±19.20） min to （0.56±0.13） min （P＜0.05）， and the dispensing time for a single prescription （excluding a part of injections and repackaged drugs） was reduced from （143.25±17.67） s to （15.24±10.08） s （P＜0.05）. The time for drug return was reduced from 129.90 （122.32， 137.00） s to 104.36 （89.91， 117.33） s（P＜0.05）； the number of drug dispensing errors decreased from 2 cases to 0 cases. After the system was launched， there were no data security incidents in our outpatient pharmacy. CONCLUSIONS The constructed closed-loop management system for the whole-process traceability of outpatient drugs can significantly enhance drug traceability accuracy and drug management quality， improve pharmacist work efficiency， and reduce drug management risks， thus providing a feasible solution for the digital transformation of hospital pharmaceutical services.

OBJECTIVE To investigate the effects of GSTP1， XRCC1， ABCB1， MTHFR gene polymorphisms on efficacy and toxic effect of chemotherapy regimen containing oxaliplatin in patients with stage Ⅲ and Ⅳ colorectal cancer patients. METHODS Clinical data of 76 patients with stage Ⅲ and Ⅳ colorectal cancer who received chemotherapy regimen containing oxaliplatin （XELOX，FOLFOX） were collected from the Second Affiliated Hospital of Soochow University from September 2018 to March 2020. The correlation of genotypes with progression-free survival （PFS） and toxic effect was analyzed by using univariate and multivariate COX regression model. RESULTS Carriers of the ABCB1 3435T＞C locus C allele （TC/CC） had a significantly higher risk of progression compared to TT genotype patients [HR＝2.39， 95%CI （1.05，5.50）， P＝0.038]. The risk of progression in patients at stage Ⅳ was significantly higher than those at stage Ⅲ [HR＝8.11， 95%CI（3.39，19.40）， P＜0.001]. Chemotherapy regimen， Karnofsky performance status score and tumor site had no significant effect on disease progression （P＞0.05）. Mutations in gene loci were not correlated with adverse reactions （P＞0.05）. CONCLUSIONS Patients carrying ABCB1 TC/CC and receiving chemotherapy regimen containing oxaliplatin have a higher risk of disease progression， which may be associated with longer PFS in patients （TT genotype） with stage Ⅳ colorectal cancer receiving the chemotherapy， while GSTP1， XRCC1， and MTHFR gene polymorphisms have no significant impact.

Objective:To observe the anti-inflammatory and glycometabolic effects of glutathione(GSH)on macrophages in collagen induced arthritis(CIA)mice.Methods:①CIA model establishment and groups:A total of 14 female DBA/1J mice were ran-domly divided into:CIA+PBS group and CIA+GSH group.The mice were sacrificed on the 50th day,collecting serum and isolating bone marrow derived macrophages(BMDM),which were marked as BMDM1.②Trained immunity model establishment and groups:BMDM were isolated from normal DBA/1J mice,and were pretreated with histone H3K27 demethylases inhibitor(GSKJ1)or PBS for 2 h.Then,serum from CIA model mice in vivo was incubated for 24 h,and the samples were grouped as follows:(CIA+GSH)+PBS group,(CIA+GSH)+GSKJ1 group,(CIA+PBS)+PBS group,(CIA+PBS)+GSKJ1 group.Lipopolysaccharide(LPS)was adopted to stimulated cells on the 6th day,which were marked as BMDM2.③RNA sequencing was used to detect differentially expressed genes(DEGs)and their function in BMDM1 and BMDM2.q-PCR was adopted to estimate the mRNA levels of PFK and Idh3g.The culture supernatants were used to measure the protein levels of TNF-α and IL-6 by ELISA.Results:①Compared with CIA+PBS group,the mice in CIA+GSH group showed lighter of joint swelling(P<0.05),less arthritis index(P<0.05),HE staining suggested less inflam-matory cell infiltration,Safranin O-fast green staining showed more chondrocytes,TRAP staining indicated reduced osteoclasts.②In BMDM1,GO analysis showed that DEGs were mainly involved in glutathione derivative metabolic process,IL-6 production,inflammatory response,innate immune response,regulation of primary metabolic process and glycolipid binding,compared with CIA+GSH and CIA+PBS group.In CIA+GSH group,the mRNA level of PFK was significantly decreased(P<0.05),while Idh3g was also significantly up-regulated(P<0.05),and the expression of TNF-α,IL-6 were both reduced(P<0.05)compared with CIA+PBS group.③In BMDM2,GO analysis showed that DEGs were also involved in inflammatory response,activation of innate immune response,regulation of tumor necrosis factor production,positive regulation of IL-6 production,regulation of glycolytic process and 1,3-β-D-glucan binding between CIA+GSH and CIA+PBS group.Furthermore,in(CIA+GSH)+PBS group,PFK was decreased(P<0.05),Idh3g was up-regulated(P<0.05),and IL-6 was also significantly down-regulated(P<0.05)compared with(CIA+PBS)+PBS group.However,there was no significant difference in the expression of Idh3g and PFK,moreover,TNF-α and IL-6 were significantly up-regulated compared with(CIA+GSH)+GSKJ1 group and(CIA+GSH)+PBS group.Conclusion:GSH can regulate glycometabolism and inflammatory response of macrophages via demethylation of histone H3K27,and it can also alleviate CIA in mice.

Objective To investigate the value of iterative decomposition of water and fat with echo asymmetry and least-squares(IDEAL-IQ)sequence in evaluating the correlation between renal ectopic fat deposition and early diabetic kidney disease(DKD)in patients with diabetes mellitus(DM).Methods A total of 51 patients with T1DM or T2DM were enrolled in this study from the Endocrinology and Metabolism Department in Affiliated Jinhua Hospital,Zhejiang University School of Medicine during January 2022 to July 2023.All the patients were divided into two groups according to the results of urine albumin creatinine ratio(UACR):normal or slightly increased urinary micro albumin group(NAU,UACR<30 mg/g,n=27)and diabetic kidney disease group(DKD,UACR 30～300 mg/g,n=24).Meanwhile,55 healthy subjects in health examination were selected as control group(NC).Pearson correlation analysis was used to analyze the correlation between renal FF and other indicators.Logistic regression analysis was used to analyze the influencing factors of early DKD,and the diagnostic efficiency of renal FF for early DKD was analyzed by the ROC curve.Results Serum creatinine(Scr)and renal fat fraction(FF)value were higher in DKD group than in NC and NAU groups(P<0.05).Pearson correlation analysis showed that kidney FF were positively correlated with UACR and Hcy(P<0.05).Logistic regression analysis showed that after adjusting for confounding factors,renal FF was a contributing factor to early DKD.The ROC curve revealed that model 2 had the highest diagnostic efficiency,with AUC=0.801,sensitivity of 66.7%,specificity of 85.2%,accuracy of 80.0%,and a renal FF cut-off value was 2.46%.Conclusion IDEAL-IQ could non-invasively measure the renal fat content in DM patients,and the renal FF were significantly associated with DKD in early stage.

OBJECTIVE: To investigate the regulatory role of the long non-coding RNA LINC00926 in pyroptosis of hypoxia-induced human umbilical vein vascular endothelial cells (HUVECs) and explore the molecular mechanism. METHODS: HUVECs were transfected with a LINC00926-overexpressing plasmid (OE-LINC00926), a siRNA targeting ELAVL1, or both, followed by exposure to hypoxia (5% O2) or normoxia. The expression of LINC00926 and ELAVL1 in hypoxia-treated HUVECs was detected using real-time quantitative PCR (RT-qPCR) and Western blotting. Cell proliferation was detected using Cell Counting Kit-8 (CCK-8), and the levels of IL-1β in the cell cultures was determined with ELISA. The protein expression levels of pyroptosis-related proteins (caspase-1, cleaved caspase-1 and NLRP3) in the treated cells were analyzed using Western blotting, and the binding between LINC00926 and ELAVL1 was verified with RNA immunoprecipitation (RIP) assay. RESULTS: Exposure to hypoxia obviously up-regulated the mRNA expression of LINC00926 and the protein expression of ELAVL1 in HUVECs, but did not affect the mRNA expression of ELAVL1. LINC00926 overexpression in the cells significantly inhibited cell proliferation, increased IL-1β level and enhanced the expressions of pyroptosis-related proteins (all P < 0.05). LINC00926 overexpression further up-regulated the protein expression of ELAVL1 in hypoxia-exposed HUVECs. The results of RIP assay confirmed the binding between LINC00926 and ELAVL1. ELAVL1 knockdown significantly decreased IL-1β level and the expressions of pyroptosis-related proteins in hypoxia-exposed HUVECs (P < 0.05), while LINC00926 overexpression partially reversed the effects of ELAVL1 knockdown. CONCLUSION LINC00926 promotes pyroptosis of hypoxia-induced HUVECs by recruiting ELAVL1.
Humans ; Caspase 1 ; ELAV-Like Protein 1 ; Human Umbilical Vein Endothelial Cells ; Pyroptosis ; RNA, Messenger ; RNA, Long Noncoding/genetics* ; Cell Hypoxia

Objective:To investigate the in vitro inhibitory effect of methylene blue mediated photodynamic therapy (PDT) combined with berberine on Porphyromonas gingivalis (P.g). Methods:P.g was cultured until the middle to late log phase, and methylene blue was added to P.g suspension at different mass concentrations for 5 min, and a laser (wavelength 660 nm, power 140 mW/cm 2) was irradiated for 2 min to find the optimal concentration of methylene blue combined with the laser for in vitro inhibition of P.g. The effect of methylene blue mediated PDT on the in vitro inhibition of P.g and the effect of berberine on the growth curve of P.g were observed. The inhibitory effect of methylene blue mediated PDT and berberine on P.g was investigated by successive combined applications. The effect of methylene blue mediated PDT on P.g morphology was observed by scanning electron microscopy. The absorption peaks of each component were measured by ultraviolet spectrophotometer. Results:The best inhibition was achieved at a methylene blue mass concentration of 24.414 1 μg/ml under 660 nm laser excitation. The differences were statistically significant in both the methylene blue and PDT groups compared with the control group (all P<0.001). 0.05 mg/ml berberine had an inhibitory effect on the planktonic bacteria of P.g. After P.g was treated with methylene blue mediated PDT, the bacterial cell walls were crumpled into clusters. Compared with the control group, the number of colonies was reduced in the 0.05 mg/ml berberine group, and the difference was statistically significant ( P<0.01). The difference between the 0.05 mg/ml berberine + light group and the control group was not statistically significant ( P>0.05). When PDT was combined with berberine, there was a synergistic inhibitory effect on P.g. PDT followed by berberine shows a better inhibitory effect on bacteria, and the differences were statistically significant (all P<0.01). After the berberine treatment, the bacterial surface became smooth, and the length of the bacterial body increased compared with the control group. Conclusions:Methylene blue mediated PDT has an inhibitory effect on P.g. When combined with berberine, it has a synergistic inhibitory effect on P.g., and the inhibition effect is better when PDT is applied first and then berberine is applied in combination.

Parvalbumin interneurons belong to the major types of GABAergic interneurons. Although the distribution and pathological alterations of parvalbumin interneuron somata have been widely studied, the distribution and vulnerability of the neurites and fibers extending from parvalbumin interneurons have not been detailly interrogated. Through the Cre recombinase-reporter system, we visualized parvalbumin-positive fibers and thoroughly investigated their spatial distribution in the mouse brain. We found that parvalbumin fibers are widely distributed in the brain with specific morphological characteristics in different regions, among which the cortex and thalamus exhibited the most intense parvalbumin signals. In regions such as the striatum and optic tract, even long-range thick parvalbumin projections were detected. Furthermore, in mouse models of temporal lobe epilepsy and Parkinson's disease, parvalbumin fibers suffered both massive and subtle morphological alterations. Our study provides an overview of parvalbumin fibers in the brain and emphasizes the potential pathological implications of parvalbumin fiber alterations.
Mice ; Animals ; Epilepsy, Temporal Lobe/pathology* ; Parvalbumins/metabolism* ; Parkinson Disease/pathology* ; Neurons/metabolism* ; Interneurons/physiology* ; Disease Models, Animal ; Brain/pathology*

The Brodmann area(BA)-based map is one of the most widely used cortical maps for studies of human brain functions and in clinical practice;however,the molecular architecture of BAs remains unknown.The present study provided a global multiregional proteomic map of the human cerebral cortex by analyzing 29 BAs.These 29 BAs were grouped into 6 clusters based on similarities in proteomic patterns:the motor and sensory cluster,vision cluster,auditory and Broca's area cluster,Wernicke's area cluster,cingulate cortex cluster,and heterogeneous function cluster.We identified 474 cluster-specific and 134 BA-specific signature proteins whose functions are closely associated with specialized functions and disease vulnerability of the corresponding clus-ter or BA.The findings of the present study could provide explanations for the functional connec-tions between the anterior cingulate cortex and sensorimotor cortex and for anxiety-related function in the sensorimotor cortex.The brain transcriptome and proteome comparison indicates that they both could reflect the function of cerebral cortex,but show different characteristics.These pro-teomic data are publicly available at the Human Brain Proteome Atlas(www.brain-omics.com).Our results may enhance our understanding of the molecular basis of brain functions and provide an important resource to support human brain research.

Objective:To establish an automatic planning method using volumetric-modulated arc therapy (VMAT) for primary liver cancer (PLC) radiotherapy based on predicting the feasibility dose-volume histogram (DVH) and evaluate its performance.Methods:Ten patients with PLC were randomly chosen in this retrospective study. Pinnacle Auto-Planning was used to design the VMAT automatic plan, and the feasibility DVH curve was obtained through the PlanIQ dose prediction, and the initial optimization objectives of the automatic plan were set according to the displayed feasible objectives interval. The plans were accessed according to dosimetric parameters of the planning target volume and organs at risk as well as the monitor units. All patients′ automatic plans were compared with clinically accepted manual plans by using the paired t-test. Results:There was no significant difference of the planning target volume D 2%, D 98%, D mean or homogeneity index between the automatic and manual plans ((58.55±2.81) Gy vs.(57.98±4.17) Gy, (47.15±1.58) Gy vs.(47.82±1.38) Gy, (53.14±0.95) Gy vs.(53.44±1.67) Gy and 1.15±0.05 vs. 1.14±0.07, all P>0.05). The planning target volume conformity index of the manual plan was slightly higher than that of the automatic plan (0.77±0.08 vs. 0.69±0.06, P<0.05). The mean doses of normal liver, V 30Gy, V 20Gy, V 10Gy, V 5Gy and V< 5Gy of the automatic plan were significantly better than those of the manual plan ((26.68±11.13)% vs.(28.00±10.95)%, (29.96±11.50)% vs.(31.89±11.51)%, (34.88±11.51)% vs.(38.66±11.67)%, (45.38±12.40)% vs.(50.74±13.56)%, and (628.52±191.80) cm 3vs.(563.15±188.39) cm 3, all P<0.05). The mean doses of the small intestine, the duodenum, and the heart, as well as lung V 10 of the automatic plan were significantly less than those of the manual plan ((1.83±2.17) Gy vs.(2.37±2.81) Gy, (9.15±9.36) Gy vs.(11.18±10.49) Gy, and (5.44±3.10) Gy vs.(6.25±3.26) Gy, as well as (12.70±7.08)% vs.(14.47±8.11)%, all P<0.05). Monitor units did not significantly differ between two plans ((710.67±163.72) MU vs.(707.53±155.89) MU, P>0.05). Conclusions:The automatic planning method using VMAT for PLC radiotherapy based on predicting the feasibility DVH enhances the quality for PLC plans, especially in terms of normal liver sparing. Besides, it also has advantages for the protection of the intestine, whole lung and heart.