OBJECTIVE: To evaluate the effect of palliative care on drug use, medical service utilization and medical expenditure of patients with advanced cancer. METHODS: A cohort of patients including pal-liative care and standard care was constructed using the medical records of the patients in Peking University Cancer Hospital from 2018 to 2020, and coarsened exact matching was used to match the two groups of patients. The average monthly opioid consumption, hospitalization rate, intensive care unit (ICU) rate and operation rate, and the average monthly total cost were selected to evaluate drug use, medical service utilization and medical expenditure. Chi-square test and Wilcoxon signed rank test were used to compare the differences between the two groups before and after exposure and the change in the palliative care group. The net impact of palliative care on the patients was calculated using the difference-in-differences analysis. RESULTS: In this study, 180 patients in the palliative care group and 3 101 patients in the stan-dard care group were finally included in the matching, and the matching effect of the two groups was good (L₁ < 0.1). Before and after exposure, the average monthly opioid consumption in the palliative care group was significantly higher than that in the standard care group (Before exposure: 0.3 DDD/person-month vs. 0.1 DDD/person-month, P < 0.01; After exposure: 0.7 DDD/person-month vs. 0.1 DDD/person-month, P < 0.01; DDD refers to defined daily dose), palliative care significantly increased the average monthly opioid consumption in the patients (0.3 DDD/person-month, P < 0.01). The hospitalization rate (48.9% vs. 74.3%, P < 0.01) and operation rate (3.9% vs. 8.8%, P < 0.01) of the patients in palliative care group were significantly lower than those in standard care group, and the ICU rate became similar between the two groups (1.1% vs. 1.6%, P=0.634). Palliative care significantly reduced the patients ' hospitalization rate (-25.6%, P < 0.01), ICU rate (-4.9%, P < 0.01) and operation rate (-14.5%, P < 0.01). Before and after exposure, the average monthly total costs of pal-liative care group were slightly higher than those of standard care group (Before exposure: 20 092.3 yuan vs. 19 132.8 yuan, P=0.725; After exposure: 9 719.8 yuan vs. 8 818.8 yuan, P=0.165). Palliative care increased the average monthly total cost by 2 208.8 yuan, but it was not statistically significant (P=0.316). CONCLUSION Palliative care can increase the opioid consumption in advanced cancer patients, reduce the rates of hospitalization, ICU and surgery, but has no significant effect on medical expenditure.
Humans ; Palliative Care/economics* ; Neoplasms/drug therapy* ; Analgesics, Opioid/economics* ; Male ; Female ; Middle Aged ; Aged ; Hospitalization/economics* ; Intensive Care Units/statistics & numerical data* ; Health Expenditures/statistics & numerical data* ; Adult ; Drug Utilization/statistics & numerical data* ; Patient Acceptance of Health Care/statistics & numerical data*

The aim of this study is to establish an gene editing method of Mesomycoplasma hyo-pneumoniae(Mhp)based on the homologous recombination principle.The restriction enzyme di-gestion and ligation method combined with gene synthesis were used to construct a shuttle plasmid to achieve replication in both Mhp and Escherichia coli(E.coli).The pGEM?-T vector was used as the skeleton.The oriC sequence of Mhp which can achieve the replication of the plasmid in Mhp was inserted into the vector.Sequences of the Spiroplasma promoter and puromycin resistance gene were then inserted into the above constructed plasmid to screen recombinant clones.The up-stream and downstream homologous arms of p97 were constructed to initiate homologous recombination.The recA gene of E.coli is inserted to improve the efficiency of homologous recom-bination.The obtained shuttle plasmid was then delivered into Mhp by electro-transformation or chemical transformation.A shuttle plasmid,pGEM?-Mhp-oriC-p 97,which can replicate in both Mhp and E.coli was constructed.With the transformation of this plasmid,the carried puromycin gene and recA gene can be expressed,the p97 gene can be edited.Finally,the genetically unstable p97 gene mutant was initially obtained.In this study,a tool for Mhp gene editing based on the principle of homologous recombination was established,which laid a foundation for the develop-ment of tools for studying the pathogenesis of Mhp.

Microplastics(particles<5 μm in diameter),generated through plastic processing or natural degradation,have emerged as novel environmental contaminants with increasing threats to ecosys-tems and human health.Recent studies have demonstrated the accumulation of microplastics in various environmental matrices,human tissues and even placentas,highlighting the urgent need to investigate their health effects.These particles enter the human system primarily through dietary intake and water consumption,yet critical knowledge gaps remain regarding their bioaccumulation potential,toxicological profiles,and synergistic interactions with co-existing environmental contaminants.The Drosophila mela-nogaster(fruit fly),a well-established model organism,offers distinct advantages for contaminant toxicity assessment,including a compact life cycle,small body size,rapid reproduction,ease of laboratory maintenance,and extensive availability of transgenic strains.In particular,its genome has a high degree of homology with the human genome,which further enhances its scientific relevance for toxicological studies.In this review,we summarize the advantages of Drosophila models in microplastic toxicity studies,with particular emphasis on recent advances in understanding intestinal toxicity,neuro toxicity,genotox-icity,reproductive toxicity,developmental toxicity,and transgenerational toxicity.We point to critical research gaps that require urgent investigation,including the bioaccumulation dynamics of microplas-tics,metabolic transformation and elimination pathways,multi-pollutant interaction effects,molecular mechanisms of toxicity,and comprehensive health risk assessment frameworks.The review aims to provide data for elucidating the mechanisms of microplastic toxicity and formulating evidence-based prevention strategies.

Objective:To analyze the epidemiological characteristics of active pulmonary tuberculosis (pulmonary tuberculosis) in Xi'an from 2013 to 2023 and predict the incidence trend of pulmonary tuberculosis in Xi'an by using autoregressive integrated moving average (ARIMA) product seasonal models to provide a decision-making basis for tuberculosis prevention and control.Methods:The incidence data of pulmonary tuberculosis reported in Xi'an from 2013 to 2023 were collected through the Tuberculosis Information Management System of the Chinese Center for Disease Control and Prevention. The Excel 2016 software was used for descriptive statistical analysis of pulmonary tuberculosis incidence data reported in Xi'an from 2013 to 2023. The SPSS 20.0 software was used to establish an ARIMA product seasonal model to predict the incidence of pulmonary tuberculosis in Xi'an.Results:A total of 49 860 cases of pulmonary tuberculosis were reported in Xi'an from 2013 to 2023, with an annual average incidence of 45.60/100 000. The incidence showed a downward trend in the past decade. The incidence was high in spring, with a peak from March to May, a small peak from November to January, and a low incidence in February and October. The annual average incidence of pulmonary tuberculosis in 2 suburban counties (52.80/100 000) was higher than that in 14 urban areas (43.21/100 000) ( χ2=20.19, P<0.001). With the increase of age, the incidence of pulmonary tuberculosis was higher, and the incidence of the males was higher than that of female ( χ2=378.34, P<0.001), the ratio of male to female incidence was 1.73∶1. The most occupation of the population was farmers, accounting for 46.54%. The established ARIMA (0, 1, 1) (1, 1, 1) 12 product seasonal model exhibited a good prediction effect, with the Bayesian Information Criterion being -1.567, the root mean square error being 0.42, and the mean absolute percentage error being 9.62. The average relative error between the actual value and the predicted value was 6.63%, and the 95% CI of the predicted value included the actual value. Conclusions:2013-2023, the incidence of pulmonary tuberculosis in Xi'an has been on the decline as a whole. Special attention should be paid to the prevention and control of tuberculosis in districts (counties) adjacent to mountainous areas in the south, people aged 60 years and above, and farmers and other vulnerable groups. The established ARIMA (0, 1, 1) (1, 1, 1) 12 product seasonal model exhibited a good predictive effect and can be applied to the short-term prediction of tuberculosis incidence.

Objective:To analyze the epidemiological characteristics of active pulmonary tuberculosis (pulmonary tuberculosis) in Xi'an from 2013 to 2023 and predict the incidence trend of pulmonary tuberculosis in Xi'an by using autoregressive integrated moving average (ARIMA) product seasonal models to provide a decision-making basis for tuberculosis prevention and control.Methods:The incidence data of pulmonary tuberculosis reported in Xi'an from 2013 to 2023 were collected through the Tuberculosis Information Management System of the Chinese Center for Disease Control and Prevention. The Excel 2016 software was used for descriptive statistical analysis of pulmonary tuberculosis incidence data reported in Xi'an from 2013 to 2023. The SPSS 20.0 software was used to establish an ARIMA product seasonal model to predict the incidence of pulmonary tuberculosis in Xi'an.Results:A total of 49 860 cases of pulmonary tuberculosis were reported in Xi'an from 2013 to 2023, with an annual average incidence of 45.60/100 000. The incidence showed a downward trend in the past decade. The incidence was high in spring, with a peak from March to May, a small peak from November to January, and a low incidence in February and October. The annual average incidence of pulmonary tuberculosis in 2 suburban counties (52.80/100 000) was higher than that in 14 urban areas (43.21/100 000) ( χ2=20.19, P<0.001). With the increase of age, the incidence of pulmonary tuberculosis was higher, and the incidence of the males was higher than that of female ( χ2=378.34, P<0.001), the ratio of male to female incidence was 1.73∶1. The most occupation of the population was farmers, accounting for 46.54%. The established ARIMA (0, 1, 1) (1, 1, 1) 12 product seasonal model exhibited a good prediction effect, with the Bayesian Information Criterion being -1.567, the root mean square error being 0.42, and the mean absolute percentage error being 9.62. The average relative error between the actual value and the predicted value was 6.63%, and the 95% CI of the predicted value included the actual value. Conclusions:2013-2023, the incidence of pulmonary tuberculosis in Xi'an has been on the decline as a whole. Special attention should be paid to the prevention and control of tuberculosis in districts (counties) adjacent to mountainous areas in the south, people aged 60 years and above, and farmers and other vulnerable groups. The established ARIMA (0, 1, 1) (1, 1, 1) 12 product seasonal model exhibited a good predictive effect and can be applied to the short-term prediction of tuberculosis incidence.

Microplastics(particles<5 μm in diameter),generated through plastic processing or natural degradation,have emerged as novel environmental contaminants with increasing threats to ecosys-tems and human health.Recent studies have demonstrated the accumulation of microplastics in various environmental matrices,human tissues and even placentas,highlighting the urgent need to investigate their health effects.These particles enter the human system primarily through dietary intake and water consumption,yet critical knowledge gaps remain regarding their bioaccumulation potential,toxicological profiles,and synergistic interactions with co-existing environmental contaminants.The Drosophila mela-nogaster(fruit fly),a well-established model organism,offers distinct advantages for contaminant toxicity assessment,including a compact life cycle,small body size,rapid reproduction,ease of laboratory maintenance,and extensive availability of transgenic strains.In particular,its genome has a high degree of homology with the human genome,which further enhances its scientific relevance for toxicological studies.In this review,we summarize the advantages of Drosophila models in microplastic toxicity studies,with particular emphasis on recent advances in understanding intestinal toxicity,neuro toxicity,genotox-icity,reproductive toxicity,developmental toxicity,and transgenerational toxicity.We point to critical research gaps that require urgent investigation,including the bioaccumulation dynamics of microplas-tics,metabolic transformation and elimination pathways,multi-pollutant interaction effects,molecular mechanisms of toxicity,and comprehensive health risk assessment frameworks.The review aims to provide data for elucidating the mechanisms of microplastic toxicity and formulating evidence-based prevention strategies.

The aim of this study is to establish an gene editing method of Mesomycoplasma hyo-pneumoniae(Mhp)based on the homologous recombination principle.The restriction enzyme di-gestion and ligation method combined with gene synthesis were used to construct a shuttle plasmid to achieve replication in both Mhp and Escherichia coli(E.coli).The pGEM?-T vector was used as the skeleton.The oriC sequence of Mhp which can achieve the replication of the plasmid in Mhp was inserted into the vector.Sequences of the Spiroplasma promoter and puromycin resistance gene were then inserted into the above constructed plasmid to screen recombinant clones.The up-stream and downstream homologous arms of p97 were constructed to initiate homologous recombination.The recA gene of E.coli is inserted to improve the efficiency of homologous recom-bination.The obtained shuttle plasmid was then delivered into Mhp by electro-transformation or chemical transformation.A shuttle plasmid,pGEM?-Mhp-oriC-p 97,which can replicate in both Mhp and E.coli was constructed.With the transformation of this plasmid,the carried puromycin gene and recA gene can be expressed,the p97 gene can be edited.Finally,the genetically unstable p97 gene mutant was initially obtained.In this study,a tool for Mhp gene editing based on the principle of homologous recombination was established,which laid a foundation for the develop-ment of tools for studying the pathogenesis of Mhp.

BACKGROUND:The research of dental stem cells in the fields of regenerative medicine and tissue engineering has been deepening,bringing hope for the repair of tooth-related tissues and the treatment of systemic diseases.However,there is a lack of systematic research and analysis on the biological characteristics of dental stem cells in different age groups. OBJECTIVE:To explore the biological characteristics of the human deciduous tooth and permanent tooth pulp stem cells cultured in umbilical cord blood platelet lysate to provide a reliable basis for human platelet lysates to replace fetal bovine serum. METHODS:The pulp tissues of deciduous teeth,juvenile permanent teeth and adult permanent teeth were taken out and cultured in DMEM/F-12 medium supplemented with 10%fetal bovine serum or different concentrations(5%,10%and 15%)of human platelet lysates.Cell proliferation in the four groups was detected by cytometry.The optimal concentration of human platelet lysates was selected for subsequent experiments.Under the optimal concentration of human platelet lysates,human deciduous tooth and juvenile and adult permanent tooth pulp stem cells were cultured in vitro.The cell growth status was observed under the microscope.The specific antigen on the cell surface was detected by flow cytometry.The cell proliferation ability was tested by the cell counting method and CCK-8 assay.The cell differentiation ability in vitro was observed by a three-line differentiation assay. RESULTS AND CONCLUSION:(1)The cell proliferation rate of the 10%human platelet lysate group was the highest.(2)In all three groups,fusiform fibrous cells grew and expanded from around the tissue block.There was no significant difference between deciduous teeth and juvenile permanent tooth cells,but the adult permanent tooth cells were larger than the deciduous and juvenile permanent tooth cells of the same generation.(3)The results of flow cytometry showed that deciduous teeth,juvenile permanent teeth and adult permanent teeth conformed to the phenotypic characteristics of mesenchymal stem cells.(4)The proliferative capacity of adult permanent dental pulp stem cells was significantly lower than those of deciduous teeth and juvenile permanent dental pulp stem cells(P<0.01).(5)mRNA expressions of osteoblast-related genes alkaline phosphatase and bone morphogenetic protein 2,lipoprotein lipase and peroxisome proliferator-activated receptor γ2,mRNA expressions of chondroblast related gene type II collagen α1 and cartilage oligomeric matrix protein in adult pulp stem cells of permanent teeth were significantly lower than those of deciduous teeth and juvenile permanent teeth pulp stem cells(P<0.01).(6)Compared with adult dental pulp stem cells,human deciduous teeth and juvenile permanent teeth dental pulp stem cells have the stronger proliferative capacity and multidirectional differentiation potential,and are more suitable for clinical research and disease treatment.

Using the amorphous solid dispersion (ASD) technology, poorly water-soluble drugs can be formulated into high-energy amorphous forms. After oral administration, a kinetic supersaturated solution is formed in the gastrointestinal tract, and oral bioavailability is thus effectively improved. As important components of ASDs, pharmaceutical excipients affect the supersaturation of ASDs. Therefore, it is significant to clarify the effects of various types of pharmaceutical excipients on the supersaturated solutions for the development of ASDs. This paper reviews the effects of polymers, small-molecule excipients, and porous materials on the supersaturated solutions formed after dissoptlution of ASD with an emphasis on the mechanisms of various types of pharmaceutical excipients on the supersaturated solutions, providing theoretical guidance for the rational selection of medicinal excipients in the development of ASDs.

Objective:To investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical study.