Background The pathogenesis of silicosis has not been fully elucidated, and microRNAs (miRNA) may be involved in the occurrence and development of silicosis. Objective To investigate the effect of miR-204-3p inhibitor on the epithelial-mesenchymal transition (EMT) process and silicosis fibrosis in silicon dioxide dust-induced alveolar epithelial cells. Methods A co-culture model of macrophages and epithelial cells was established using a Transwell chamber. NR8383 macrophages were seeded into the upper chamber of the Transwell, and RLE-6TN cells were seeded into the lower chamber. After 24 h of culture, the medium in the lower chamber was discarded, washed three times with phosphate-buffered saline (PBS), and replaced with serum-free medium. The cells were divided into four groups: control group, silicosis group, miRNA NC group, and miR-204-3p inhibitor group. The lower chamber was transfected with miRNA NC for the miRNA NC group or the miR-204-3p inhibitor for the miR-204-3p inhibitor group. The lower chambers of the remaining two groups were added by equal amounts of serum-free medium. After 24 h, except for the control group that received an equal volume of serum-free medium, the upper chambers of the remaining three groups were treated with 800 μg·mL⁻¹ silicon dioxide dust. Morphological changes in each group were observed under a microscope. The mRNA and protein expression levels of EMT-related factors, including α-smooth muscle actin (α-SMA), Vimentin, N-Cadherin, and E-Cadherin, were detected by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and Western blot. The mRNA and protein expression levels of fibrosis-related factors, including Collagen I, Collagen III, and Fibronectin, were also assessed by RT-qPCR and Western blot. The fluorescence expression intensities of α-SMA, N-Cadherin, and E-Cadherin were evaluated by immunofluorescence. Results The morphological observation revealed that RLE-6TN cells in the control group exhibited a regular oval shape. After treatment with silicon dioxide, the cells predominantly displayed a long spindle shape. Following the intervention with the miR-204-3p inhibitor, the number of long spindle-shaped cells increased, and the intercellular gaps widened. The RT-qPCR results showed that, compared with the control group, the silicosis group exhibited significantly higher relative mRNA expression levels of EMT-related markers (α-SMA, Vimentin, and N-Cadherin) (P<0.05), while the relative mRNA expression level of E-Cadherin was significantly reduced (P<0.05); the relative mRNA expression levels of fibrosis-related markers (Collagen I, Collagen III, and Fibronectin) were also significantly elevated (P<0.05). Compared with the miRNA NC group, the miR-204-3p inhibitor group showed significantly increased relative mRNA expression levels of α-SMA, Vimentin, and N-Cadherin (P<0.05), decreased E-Cadherin mPNA expression (P<0.05), and elevated mPNA expression of Collagen I, Collagen III, and Fibronectin (P<0.05). The Western blot analysis indicated that, compared with the control group, the silicosis group had significantly higher protein expression levels of α-SMA, Vimentin, and N-Cadherin (P<0.05), lower E-Cadherin protein expression (P<0.05), and increased protein expression of Collagen I, Collagen III, and Fibronectin (P<0.05). Compared with the miRNA NC group, the miR-204-3p inhibitor group exhibited significantly elevated protein expression levels of α-SMA, Vimentin, and N-Cadherin (P<0.05), reduced E-Cadherin expression (P<0.05), and increased protein expression of Collagen I, Collagen III, and Fibronectin (P<0.05). The immunofluorescence analysis demonstrated that, compared with the control group, the silicosis group showed enhanced fluorescence intensities of α-SMA and N-Cadherin and reduced fluorescence intensity of E-Cadherin. Compared with the miRNA NC group, the miR-204-3p inhibitor group exhibited increased fluorescence intensities of α-SMA and N-Cadherin and decreased fluorescence intensity of E-Cadherin. Conclusion The miR-204-3p inhibitor may exacerbate the EMT process and silicosis fibrosis in silicon dioxide-induced RLE-6TN cells. miR-204-3p plays a negative regulatory role in silicosis fibrosis.

This study investigated the effect of different carrier materials on the in vitro properties of progesterone solid dispersions. The solid dispersions of the insoluble drug progesterone were prepared by hot melt extrusion technique using rheological properties as the index of investigation, and the in vitro properties of the solid dispersions were characterized. Scanning electron microscope revealed solid dispersions with rough surfaces and agglomerated microstructures into irregular lumpy particles. Differential scanning calorimetry and powder X-ray diffraction showed the change of progesterone crystalline form in solid dispersions from crystalline to amorphous state. In vitro dissolution studies showed that solid dispersions prepared with different carrier materials can effectively improve the dissolution rate of drugs. The results of the study showed that the type of carrier material had a significant effect on the in vitro properties of solid dispersions, providing a reference for the study of solid dispersions in the controlled release of insoluble drugs.

BACKGROUND:Our previous studies found that the polypeptide of Cornus cervi Colla can promote bone growth,which has a good application prospect in the treatment of bone diseases.However,how Cornus cervi Colla works in the body and the principle are not clear. OBJECTIVE:To study the in vivo distribution and tracing of Cornus cervi Colla using fluorescence labeling and tracer technique. METHODS:Cornus cervi Colla was fluorescently labeled using fluorescein isothiocyanate,and the labeling results were detected by fluorescence imaging and UV spectral scanning.Successfully labeled Cornus cervi Colla was injected into mice by gavage,and the absorption of Cornus cervi Colla into blood was detected by laser confocal microscopy,and the distribution of Cornus cervi Colla in mice was detected by small animal in vivo imager.The distribution of Cornus cervi Colla in the mice was detected by laser confocal microscopy.Samples were taken from serum and bone at the time of the strongest fluorescence,and gel electrophoresis was carried out on serum and bone tissue protein solutions,and the components of Cornus cervi Colla absorbed into target organs were determined by secondary mass spectrometry. RESULTS AND CONCLUSION:The fluorescent markers were successfully separated by dextran gel chromatography,and the fluorescence imaging and ultraviolet spectrum scanning proved that the labeling was successful,and the fluorescence substitution degree of FITC-labeled Cornus cervi Colla was 0.953%.The fluorescence intensity of the components of Cornus cervi Colla in the blood showed that Cornus cervi Colla was most distributed in serum after oral administration for 2 hours.The fluorescence images of mice at different times were the same as those of bilateral femur and tibia,indicating that Cornus cervi Colla could play a role by entering the bone.Compared with UniProt database,secondary mass spectrometry showed that the peptide was a characteristic fragment of decorin.It is proved that decorin in Cornus cervi Colla can enter the bone to play a therapeutic role.

Objective To explore the efficacy of camrelizumab injection combined with transcatheter arterial chemoembolization(TACE)in the treatment of patients with primary liver cancer.Methods Patients with primary liver cancer were retrospectively studied and divided into control group and treatment group according to different treatment regimens.The control group was treated with TACE,while the treatment group was intravenously injected with 200 mg of camrelizumab injection once every 3 weeks on the 3rd day-7th day after first TACE on the basis of treatment in control group.All patients were treated for 12 weeks.The efficacy[objective response rate(ORR),disease control rate(DCR)],liver function[total bilirubin(TBil),glutamic oxalacetic transaminase(GOT),glutamic pyruvic transaminase(GPT)],serum tumor-related markers[alpha fetoprotein(AFP),hepatocyte growth factor(HGF),intercellular adhesion moleclar-1(ICAM-1)],T lymphocyte subsets(CD4+/CD8+ratio)and the safety was evaluated.Results There were 38 cases in treatment group and 42 cases in control group.After treatment,the ORR in treatment group and control group were 65.79％(25 cases/38 cases)and 42.86％(18 cases/42 cases),the DCR were 89.47％(34 cases/38 cases)and 71.43％(30 cases/42 cases),the differences were statistically significant(all P＜0.05).After treatment,serum TBil levels in treatment group and control group were(18.34±5.52)and(21.03±6.32)μmol·L-1;GOT levels were(54.79±17.07)and(60.57±18.29)U·L-1;GPT levels were(47.23±6.15)and(54.48±7.68)U·L-1;serum AFP levels were(96.94±28.17)and(152.49±41.22)ng·mL-1;HGF levels were(75.08±8.26)and(90.17±9.03)ng·mL-1;ICAM-1 levels were(432.38±131.43)and(526.15±184.36)ng·mL-1,respectively;CD4+/CD8+ratios were 1.31±0.23 and 1.16±0.21,respectively(all P＜0.05).Compared with the control group,the above indexes in treatment group were statistically significant(all P＜0.05).The adverse drug reactions in the treatment group were mainly reactive cutaneous capillary hyperplasia,gastrointestinal reaction and hand-foot syndrome,while the adverse drug reactions in the control group were mainly hand-foot syndrome and gastrointestinal reaction.The incidence of reactive cutaneous capillary hyperplasia in test group and control group was 52.63％and 0,the difference was statistically significant(P＜0.05).Conclusion Camrelizumab injection combined with TACE has significant efficacy in the treatment of patients with primary liver cancer.It can effectively reduce the levels of serum AFP,HGF and ICAM-1,and improve the immune function.

Objective:To analyze the epidemiological characteristics and pathogen spectrum of influenza outbreaks in Shaanxi Province from 2014 to 2023 and provide basis reference for strengthening regional influenza prevention and control.Methods:The data were collected from the Public Health Emergency Management Information System of the China Disease Prevention and Control Information System and the China Influenza Surveillance Information System. On-site epidemiological investigation information and etiological test results of influenza network laboratories reported in Shaanxi Province during 2014-2023 were collected, and descriptive analysis was conducted on the time, region, and location distribution of influenza outbreaks. SPSS 25.0 software was used for statistical analysis.Results:A total of 386 influenza outbreaks were reported in Shaanxi from 2014 to 2023, with a total attack rate of 1.81% (14 880/821 001). The epidemic peaks mainly occurred in winter and spring (November to March of the following year), and there was an alternating pattern of epidemic peaks in different years (the early peak was in December, and the late peak was in March of the following year). The epidemic areas were mainly concentrated in the Qinba Mountains of southern Shaanxi (209, 54.15%) and Guanzhong Plain (173, 44.82%). The epidemic places were mainly distributed in primary schools (239, 61.92%), and the differences of epidemic areas and places were statistically significant (all P<0.001). Influenza A(H3N2) viruses were the predominant pathogen in the outbreak (849, 57.76%), and influenza A(H3N2), B (Victoria) lineage and A(H1N1)pdm09 virus alternately dominated the epidemic peak in different years. Conclusions:The peak of influenza outbreaks in Shaanxi Province was winter and spring during 2014-2023. Primary schools in the Qinba Mountains of southern Shaanxi and Guanzhong Plain should be targeted for prevention and control. In the prevention and control programs, close attention should be paid to the changing trend of dominant strains. Effective intervention measures should be targeted to the high-incidence areas and seasons.

By sorting out the differences and connections between family doctor teams and specialized disease teams, role competency and mutual collaboration, and introducing the learning health system (LHS) mechanism, a comprehensive operating system for community general practice learning organizations based on LHS was constructed, focusing on five single disease types. The system includes a combination of general and specialized medicine that links three levels of medical institutions, thereby opening up the business cooperation process between professionals in different institutions, and establishing a sustainable collaboration mechanism. This allows medical institutions at three levels to continuously tap the potential of their disciplines, achieve their own ability growth and feel higher work value, and also bring better health solutions to residents, guided by the common goal of "health centered, patient centered".

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

Objective To analyze the atrioventricular synchronization rate after implantation of Micra AV leadless pacemaker,and the impact of postoperative programming optimization on atrioventricular synchronization rate.Methods A prospective cohort study was conducted to select patients with complete atrioventricular block who underwent Micra AV leadless pacemaker implantation at Beijing Anzhen Hospital from August 2022 to June 2023.Programming optimization were performed at 1 week,1 month,and 3 months postoperatively,and atrioventricular synchronization rate,electrical parameters,and echocardiography were recorded.Results A total of 68 patients with complete atrioventricular block implanted with Micra AV were selected,with an average age of(68.2±9.7)years,including 47 males(69.1％).All patients were successfully implanted with Micra AV,and there were no serious postoperative complications;The average threshold,sense,and impedance parameters were stable during 1 week,1 month,and 3 months after the procedure;There was no significant difference in the EF value of postoperative echocardiography(P=0.162);The average atrioventricular synchronization rates at 1 week,1 month,and 3 months postoperatively were(75.2％vs.83.8％vs.91.6％,P=0.001).Conclusions As an mechanical atrial sensing,Micra AV requires personalized adjustment of relevant parameters;Postoperative follow-up programming optimization plays an important role in the atrioventricular synchronization and comfort level in patients with complete atrioventricular block after implantation of Micra AV leadless pacemaker.

Human viral respiratory disease is a kind of widely prevalent infectious disease. The incidence rate of respiratory virus infection occupies a major position in the overall structure of global incidence rate of residents, and is one of the main causes of acute and fatal human diseases. Natural products have diverse structures and novel mechanisms of action, which can regulate body immunity and resist respiratory viruses, and have unique advantages in the treatment of respiratory viral diseases. This article summarizes the current research progress of natural drugs in the prevention and treatment of respiratory viruses, classifies the action mechanism of the active components of natural drugs against respiratory viruses, to provide reference basis for clinical treatment and drug discovery of respiratory diseases in the future.

The incidence of intrahepatic cholangiocarcinoma (ICC) continues to rise, and there are no effective drugs to treat it. The immune microenvironment plays an important role in the development of ICC and is currently a research hotspot. Icaritin (ICA) is an innovative traditional Chinese medicine for the treatment of advanced hepatocellular carcinoma. It is considered to have potential immunoregulatory and anti-tumor effects, which is potentially consistent with the understanding of "Fuzheng" in the treatment of tumor in traditional Chinese medicine. However, whether ICA can be used to treat ICC has not been reported. Therefore, in this study, sgp19/kRas, an in situ ICC mouse model with intact immune system, was selected to evaluate the efficacy of ICA in the treatment of ICC in vivo for the first time, and the effects of ICA on the tumor immune microenvironment of ICC mice were analyzed by flow cytometry. This experiment was approved by the Experimental Animal Ethics Committee of Capital Medical University (approval number: AEEI-2023-138). In this study, sgp19/kRas ICC mouse model was treated with oral gavage of 100 mg·kg^-1 ICA. We found that ICA significantly inhibited tumor growth and tumor cell proliferation in the sgp19/kRas ICC mouse model after 3 weeks of treatment. Flow cytometry analysis indicated that ICA treatment markedly reduced the proportion of M2 macrophages and increased the number of CD3⁺CD4⁺ T cells. In vitro experiments demonstrated that ICA promoted macrophage polarization towards the M1 phenotype while inhibiting polarization towards the M2 phenotype. Furthermore, transcriptomic analysis suggested that ICA enhanced Toll-like receptor 9 (TLR9) expression, influencing macrophage nitric oxide metabolism synthesis pathways and receptor-related activities, thereby regulating macrophage polarization. In summary, this study demonstrates that ICA treatment significantly delays tumor progression in sgp19/kRas ICC mouse models. Mechanistically, ICA may achieve its anti-ICC effects by upregulating TLR9 receptor expression levels, promoting macrophage polarization towards the M1 phenotype, and altering the tumor immune microenvironment.