The exploration and pilot studies of applying blockchain to drug supply chain show great potential in promoting information sharing, collaboration competence among the actors, regulatory efficiency, and etc. In the future, with the help of blockchain, the optimization of the entire supply chain for orphan drugs is expected to be realized. However, there is no such exploration in China at present. This paper systematically sorts out the whole process of supply chain for orphan drugs and the existing problems of the chain. The article concludes that at present, blockchain is mainly used in the " circulation" and " use" of the drug supply chain. It helps to improve the traceability of drugs, to cope with the problem of counterfeit drugs, to enable actors of the drug supply chain to form a collaborative network in optimizing resource allocation, and to improve the operation and supervision efficiency of the supply chain. In the future, the application faces challenges such as high costs in system conversion, lack of personnel awareness, and incomplete supporting systems. Based on the three dimensions of technology, practice, and research, this paper also looks into the future and suggests for the future use of blockchain in the supply chain of orphan drugs by constructing a practice model, the so called DI-GIVE (Digital, Intelligence, Government′s supervision, Innovation, Views of variety, Evaluation-based) hoping to innovate the supply chain of orphan drugs and to ensure the drug use for the patients with rare diseases in China.

Salvia miltiorrhiza Bunge （Lamiaceae） is a medicinal plant widely used in Traditional Chinese Medicine for treating cardiovascular and cerebrovascular diseases. Chloroplasts are double-membrane-bound, chlorophyll-containing organelles and responsible for photosynthesis in plant cells. The structural information of chloroplast genomes serves as the foundation for precise exogenous gene insertion, site selection, and chloroplast genome modification. In this study, a comprehensive analysis and comparison of 125 chloroplast genomes from S. miltiorrhiza and 76 congeneric species were conducted, focusing on sequence characteristics, codon usage bias, simple sequence repeats （SSRs）, contraction/expansion of chloroplast genome boundaries, and phylogenetic relationships, which could provide a theoretical foundation for advancing chloroplast genetic engineering, genetic diversity analysis, molecular breeding, and species identification within the Salvia genus.

Objective To explore the efficacy of progressive exercise training based on the modified Medical Research Council dyspnea scale (mMRC) grading in respiratory rehabilitation for patients with chronic obstructive pulmonary disease (COPD) at a primary healthcare setting. Methods A total of 106 patients with COPD admitted to Zhuanqiao Community Health Service Center in Shanghai from Aug.1, 2022 to Jul. 30, 2024 were selected as research subjects. They were randomly divided into a study group and a control group in a 1∶1 ratio, with 53 patients in each group. The control group received conventional treatment, while the study group received conventional treatment combined with progressive exercise training. After 4 weeks of continuous treatment, the changes in the 6-minute walk test (6MWT), COPD assessment test (CAT) score, mMRC grading, Global Initiative for Chronic Obstructive Lung Disease (GOLD) grading and pulmonary function were compared between the two groups. Results Patients in both groups showed improvements in 6MWT distance, CAT score, mMRC grading, GOLD grading, and pulmonary function compared to baseline (P＜0.05). Moreover, the study group had better improvements in 6MWT distance, CAT score, mMRC grading, GOLD grading, and pulmonary function than the control group (P＜0.05). Conclusions Conventional treatment combined with progressive exercise training based on mMRC grading can enhance the effect of respiratory rehabilitation in patients with COPD, particularly in improving pulmonary function and exercise tolerance.

Imprinted genes play a key role in regulating mammalian placental and embryonic development. Here, we generated glutaminyl-peptide cyclotransferase-knockout (Qpct^-/-) mice utilizing the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) platform and identified Qpct as a novel anti-angiogenic factor in regulating mouse placentation. Compared with Qpct^+/+ mice, placentae and embryos (Qpct^-/+ and Qpct^-/-) showed significant overgrowth at embryonic Day 12.5 (E12.5), E15.5, and E18.5. Using single-cell transcriptome analysis of 32 309 cells from Qpct^+/+ and Qpct^-/- mouse placentae, we identified 13 cell clusters via single-nucleus RNA sequencing (snRNA-seq) (8880 Qpct^+/+ and 13 577 Qpct^-/- cells) and 20 cell clusters via single-cell RNA sequencing (scRNA-seq) (6567 Qpct^+/+ and 3285 Qpct^-/- cells). Furthermore, we observed a global up-regulation of pro-angiogenic genes in the Qpct^-/- background. Immunohistochemistry assays revealed a notable increase in the number of blood vessels in the decidual and labyrinthine layers of E15.5 Qpct^-/+ and Qpct^-/- mice. Moreover, the elevation of multiple pairs of ligand-receptor interactions was observed in decidual cells, endothelial cells, and macrophages, promoting angiogenesis and inflammatory response. Our findings indicate that loss of maternal Qpct leads to altered phenotypic characteristics of placentae and embryos and promotes angiogenesis in murine placentae.
Animals ; Female ; Pregnancy ; Mice ; Placentation/genetics* ; Single-Cell Analysis ; Gene Expression Profiling ; Mice, Knockout ; Transcriptome ; Placenta/blood supply* ; Neovascularization, Pathologic/genetics* ; Genomic Imprinting ; Single-Cell Gene Expression Analysis ; Angiogenesis

Objective:To study the life characteristics and related risk factors of patients with depression in Shandong Province.Methods:Based on the 2015 mental epidemiological survey database in Shandong Province,a total of 832 patients with depression,807 high-risk individuals with depression,and 819 low-risk individuals were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition(DSM-Ⅳ)and the Structured Clinical Interview for DSM-Ⅳ-TR Axis I Disorders,Research Version(SCID-I/P).In 2020,SCID-I/P was used for re diagnosis,and the General Health Questionnaire(GHQ-12),Simple Quality of Life question-naire,Pittsburgh sleep quality index(PSQI),Childhood Trauma Questionnaire(CTQ),Social Support Rating Scale(SSRS),Global Pain Scale(GPS),Montreal Cognitive Assessment(MoCA),Simplified Coping Style Question-naire(SCSQ)were used for evaluation.Compare changes in the quality of life of depression patients and construct a risk factor model.Results:Patients with depression had lower scores on the simple quality of life questionnaire at baseline and at retest after 5 years than those in the high-and low-risk groups,those in remission of depression had higher scores on the simple quality of life questionnaire at baseline and at retest after 5 years than those in non-re-mission,and those with new-onset disorder in the high-and low-risk groups had lower scores on the simple quality of life questionnaire at baseline and at retest after 5 years than those with no-onset disorder(Ps＜0.001).Depres-sion diagnosis and PSQI scale scores at baseline negatively predicted at retest after 5 years(β=-0.06,-0.15),while coping style tendencies at baseline positively predicted(β=0.06).The simple quality of life questionnaire at baseline negatively predicted depression diagnosis at retest after 5 years,GHQ-12 scores at retest after 5 years,and PSQI scale scores at retest after 5 years(β=-0.11,-0.17,-0.09),while the simple quality of life question-naire at baseline positively predicted coping style tendencies at retest after 5 years(β=0.13).Depression diagnosis at retest after 5 years,GHQ-12 scores at retest after 5 years,PSQI scale scores at retest after 5 years,coping style tendencies at retest after 5 years,SSRS scale scores,CTQ scale scores,GPS scale scores,and the simple quality of life questionnaire at baseline all influenced the simple quality of life questionnaire at retest after 5 years through ei-ther direct or indirect pathways.Conclusion:It suggest that the quality of life is lower in patients with depression than in the general population.Depression diagnosis,sleep,mental health,pain,social support,childhood trauma and coping are direct and indirect risk factors affecting life.

Objective:To evaluate changes in operational effectiveness after the implementation of ambulatory surgical management in pars plana vitrectomy (PPV).Methods:A retrospective clinical study. 17 528 surgeries in 10 895 eyes of 10 895 patients who underwent minimally invasive PPV on an ambulatory and/or inpatient basis at Tianjin Medical University Eye Hospital from August 2015 to June 2023 were included in this study. Among them, 5 346 eyes in 5 346 cases were male; 5 549 eyes in 5 549 cases were female. The age ranged from 0 to 95 years, with the mean age of (57.74±13.15) years. 6 381 surgeries in 3 615 eyes from August 2015 to December 2018 (the initial period of day surgery) were used as the control group; 11 147 surgeries in 7 280 eyes from January 2019 to June 2023 (the expanded period of day surgery) were used as the observation group. According to the management mode of ambulatory surgery, the observation group was subdivided into the decentralized management group (January 2019 to December 2020) and the centralized management group (January 2021 to June 2023), with 2 905 and 4 375 eyes and 4 646 and 6 501 surgeries, respectively. Changes in the percentage of day surgery, average hospitalization days, and average unplanned reoperation rate were compared. The Mann-Whitney U test was used to compare numerical variables between groups; the chi-square test or Fisher's exact test was used to compare categorical variables. Results:The number of cases of daytime PPV performed in the observation group and control group was 7 852 (70.44%, 7 852/11 147) and 24 (0.38%, 24/6 381) cases, respectively, and the average hospitalization days were 1 (1) and 5 (3) d. Compared with the control group, the observation group had a significantly higher percentage of day surgery ( χ2=8 051.01) and a considerably lower mean hospitalization day ( Z=4 536 844.50), and the differences were statistically significant ( P<0.000 1). The mean hospitalization days in the decentralized and centralized management groups were 2 (3) and 1 (0) d, respectively, and unplanned reoperations were 34 (0.73%, 34/4 646) and 171 (2.63%, 171/6 501) eyes, respectively. Compared with the decentralized management group, average hospitalization days was significantly lower ( Z=1 436.94) and unplanned reoperation rate was significantly higher ( χ2=54.10) were significantly lower in the centralized management group, both of which were statistically significant ( P<0.000 1). Conclusion:PPV ambulatory management model can significantly reduce the average hospitalization day, but also results in higher rates of unplanned reoperations.

ObjectiveTo investigate the effect of circSLC8A1_005 on the fibrotic phenotype of cardiac fibroblasts and the potential mechanism involved. MethodsThe effect of adenovirus-mediated overexpression of circSLC8A1_005 on the expression of fibrosis-related genes， collagen type I alpha 1 chain （Col1a1）， collagen type Ⅲ alpha 1 chain （Col3a1） and smooth muscle actin alpha 2 （Acta2）， in mouse cardiac fibroblasts （mCFs） were detected. The proliferation and migration activities of mCFs were detected by EdU and wound-healing assay， respectively. Dual luciferase reporter gene assay was performed to detect the activity of potential internal ribozyme entry site （IRES） in circSLC8A1_005. CircSLC8A1_005-translated protein， SLC8A1-605aa， and its intracellular distribution was identified by Western blot assay. The effect of SLC8A1-605aa protein on transcription activity of Sod2 gene was detected by the dual luciferase reporter gene assay. RNA binding protein immunoprecipitation （RIP） was utilized to verify the interaction between SLC8A1-605aa and superoxide dismutase 2 （Sod2） mRNA. Actinomycin D treatment was used to detect the effect of SLC8A1-605aa on Sod2 mRNA stability in mCFs. ResultsAn efficient adenovirus-mediated overexpression of circSLC8A1_005 was achieved in mCFs. The enforced expression of circSLC8A1_005 suppressed proliferation and migration of mCFs， and inhibited the expression of fibrosis-related genes in mCFs. The dual luciferase reporter gene assay revealed the activities of 2 IRES in circSLC8A1_005. Results of Western blot assay showed that circSLC8A1_005 could translate protein SLC8A1-605aa with the prospected molecular weight of 70 ku， which is predominantly distributed in the nucleus. Overexpression of the circSLC8A1_005 and SLC8A1-605aa could consistently inhibit the fibrotic phenotype of mCFs. SLC8A1-605aa could up-regulate superoxide dismutase 2 （Sod2） expression， but not at the transcriptional level. RIP assay indicated that SLC8A1-605aa could specifically interact with Sod2 mRNA， and the results of actinomycin D assay showed that SLC8A1-605aa could enhance the stability of Sod2 mRNA in mCFs. ConclusionCircSLC8A1_005 inhibits the fibrotic phenotype of cardiac fibroblasts via translating SLC8A1-605aa protein， and SLC8A1-605aa may be a potential target for the treatment of myocardial fibrosis.

AIM:To investigate the effect of circular RNA MYO9A-006(circMYO9A_006)on hypertrophic phenotype of cardiomyocytes and the underlying mechanism.METHODS:The effect of adenovirus-mediated overexpres-sion of circMYO9A_006 on the expression of hypertrophy-related proteins,including β-myosin heavy chain(β-MHC),skeletal muscle actin alpha 1(ACTA1)and atrial natriuretic peptide(ANP),was evaluated in neonatal mouse ventricular cardiomyocytes(NMVCs).Moreover,a neonatal rat ventricular cardiomyocyte(NRVC)model of phenylephrine(PE)-in-duced hypertrophy was established.The effect of circMYO9A_006 overexpression on NRVC size was ascertained using Phalloidin-iFluor 647 staining method.Dual-luciferase reporter assay was employed to measure the activity of potential in-ternal ribosome entry sites(IRES)in circMYO9A_006.The translation and intracellular location of the circMYO9A_006-translated protein,MYO9A-208aa,were verified using Western blot.To investigate the role of MYO9A-208aa in the ef-fect of circMYO9A_006 on the cardiomyocyte hypertrophic phenotype,we prepared and used the following adenoviruses:the recombinant circMYO9A_006-ORF adenovirus to express MYO9A-208aa,the recombinant circMYO9A_006-ATG-mut adenovirus that does not express MYO9A-208aa,the recombinant circMYO9A_006 adenovirus,and the adenovirus vector control.These were then employed to infect NRVCs.RESULTS:Successful adenovirus-mediated overexpression of circMYO9A_006 was observed in NMVCs.The increased expression of circMYO9A_006 notably reduced the expres-sion of hypertrophy-related proteins in NMVCs(P<0.01).Concurrently,overexpression of circMYO9A_006 substantially reduced the expression of hypertrophy-associated proteins and diminished the size of PE-induced NRVCs(P<0.05).Dual-luciferase reporter assay identified the activity of 2 IRES in circMYO9A_006.Western blot results indicated that circ-MYO9A_006 could produce the MYO9A-208aa protein with an anticipated molecular weight of 28 kD in NRVCs,primari-ly found in the cytoplasm.Elevated expression of both circMYO9A_006 and MYO9A-208aa consistently reduced the ex-pression of hypertrophy-associated proteins(P<0.01),and counteracted the enlarged size of PE-induced NRVCs(P<0.05).However,increased expression of circMYO9A_006-ATG-mut did not counteract the PE-induced hypertrophic phe-notype of NRVCs.CONCLUSION:circMYO9A_006 attenuates the hypertrophic phenotype of cardiomyocytes by synthe-sizing the MYO9A-208aa protein.

Molecularly defined renal carcinoma is a pathologic subtype of renal cell cancer (RCC) with a definite driver gene, which was first proposed in the 2022 WHO classification of tumors of the urinary system and male reproductive organs. The fumarate hydratase-deficient renal cell carcinoma and SMARCB1-deficient renal medullary carcinoma are highly aggressive and lethal subtypes. Due to the low incidence and lack of research on the mechanism, there is almost no effective treatment for these aggressive RCC subtypes. Cytoreductive nephrectomy or metastasectomy are important methods to improve the survival and quality of life of metastatic RCC patients under effective systemic therapy. However, for the highly aggressive RCC, the clinical value of the above surgical strategies is still unclear. In this review, we will discuss these problems in order to provide reference for the improvement of prognosis for patients with highly aggressive RCC subtypes.

Objective:To investigate the effect of ginkgo biloba extract (GBE) on oxidative stress in medial prefrontal cortex and excitatory/inhibitory balance of pyramidal neurons in chronic unpredictable mild stress (CUMS)-induced depressive model mice.Methods:Totally 48 SPF grade 7-week-old male C57BL/6J mice were divided into 4 groups according to random number table method: control+ saline group (CTRL+ Veh), control+ GBE group (CTRL+ GBE), model+ saline group (CUMS+ Veh), model+ GBE group (CUMS+ GBE), with 12 mice in each group.Mice in CUMS+ Veh group and CUMS+ GBE group were established by CUMS method, and mice in CTRL+ GBE group and CUMS+ GBE group were intraperitoneally injected with GBE (70 mg/kg) once a day, and mice in CTRL+ Veh group and CUMS+ Veh group were injected intraperitoneally with 0.9% sodium chloride solution.Then, the sucrose preference test, forced swimming test (FST) and tail suspension test (TST) were performed to evaluate the depressive-like behavior of mice, and open field test (OFT) was performed to evaluate the autonomous locomotion and exploration ability and anxiety-like behavior.The content of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) in mPFC were determined by ELISA.Spontaneous excitatory postsynaptic currents (sEPSC) and spontaneous inhibitory postsynaptic currents (sIPSC) were detected by whole-cell recording.SPSS 23.0 was used for data analysis and two-factor analysis of variance(whether to get GBE, whether to mold, show as GBE×CUMS) was used for statistical analysis.Results:(1) Behavioral results: the the time spent in center and total distance of OFT and sugar preference rate of the four groups of mice were compared, and the interaction of GBE×CUMS was significant( F=24.90, 4.82, 3.91, all P<0.05). The results of simple effect analysis showed that the time spent in center ((47.15±3.58) s), the total distance((19.33±0.86) m) and the sugar preference rate((59.11±8.79)%) of the mice in CUMS+ Veh group were lower than those in the CTRL+ Veh group((61.55±2.49) s, (23.24±1.21) m, (84.02±7.45) %) (all P<0.01), and the above indexes in CUMS+ GBE group ((56.51±3.53) s, (20.75±1.31) m, (70.80±11.79)%) were higher than those in CUMS+ Veh group (all P<0.05). In the immobility time of FST and TST of mice in the 4 groups, the interaction of GBE×CUMS were significant( F=85.53, 83.39, both P<0.01). The immobility time of FST and TST in CUMS+ Veh group were higher than those in CTRL+ Veh group (both P<0.01 ), and the above indexes in CUMS+ GBE group were lower than CUMS+ Veh group(both P<0.05). (2)The results of ELISA showed that the interaction of GBE×CUMS of SOD level of mice in the 4 groups was not significant ( F=3.52, P=0.07), but the main effects of GBE factor and CUMS factor were both significant ( F=4.69, 46.93, both P<0.05). The interaction of GBE×CUMS of MDA level was significant( F=16.61, P<0.01). The level of SOD in the CUMS+ Veh group was lower than that in the CTRL+ Veh group ( P<0.01), and the level of SOD in the CUMS+ GBE group was higher than that in the CUMS+ Veh group ( P<0.05). The level of MDA in the CUMS+ Veh group was higher than that of the CTRL+ Veh group ( P<0.01), and the level of MDA in CUMS+ GBE group was lower than that of the CUMS+ Veh group ( P<0.01). (3) The results of whole-cell recording showed that the interaction of GBE×CUMS of frequency and quantification of sEPSC in the four groups were significant ( F=5.45, 6.94, both P<0.05). The sEPSC frequency and quantification in the CUMS+ Veh group were lower than those in the CTRL+ Veh group (both P<0.01), and the sEPSC frequency and quantification in CUMS+ GBE group were higher than those of CUMS+ Veh group (both P<0.05). The interaction of GBE×CUMS of frequency and quantification of sIPSC in the four groups were significant ( F=7.78, 8.96, both P<0.01). The sIPSC frequency and quantification of the CUMS+ Veh group were higher than those of CTRL+ Veh group (both P<0.01), and the above indexes of CUMS+ GBE group were lower than those of CUMS+ Veh group (both P<0.01). As for the sEPSC/sIPSC ratio, GBE×CUMS interaction was significant ( F=5.45, P=0.02). The sEPSC/sIPSC ratio of CUMS+ Veh group (0.09±0.01) was lower than that of CTRL+ Veh group (0.28±0.04) ( P<0.01), and the sEPSC/sIPSC ratio of CUMS+ GBE group (0.14±0.03) was higher than that of CUMS+ Veh group ( P<0.05). Conclusion:Ginkgo biloba extract can improve the depression-like behavior of mice induced by CUMS, reduce the oxidative stress of mPFC and improve the excitation/inhibition balance of pyramidal neurons in depressive model mice.