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.

Humans ; Adolescent ; Acne Vulgaris/therapy* ; Skin Care ; Surveys and Questionnaires ; Cognition ; China ; Skin

Natural products are important sources of drug discovery. However, the traditional methods of extraction and isolation, as well as chemical synthesis for obtaining natural products are associated with issues such as operational complexity, high costs, low efficiency, and environmental pollution. Constructing microbial cell factories through synthetic biology methods to produce medicinal natural products has the advantages of high efficiency, low cost, and environmental protection. Nevertheless, the scope and yield improvement of the products are limited by the limitations of enzymes in microbial cell factories. Protein engineering is considered one of the most effective approaches to overcome these limitations. This article introduces commonly used methods of protein engineering technology and summarizes its specific applications in improving enzyme performance, modifying the enzymatic environment, and promoting the development of synthetic biology tools in the field of pharmaceutical natural product synthesis. Furthermore, it analyzes the current bottlenecks and challenges in protein engineering and looks forward to its future application prospects, offering insights for the development and practical use of protein engineering technology.

Objective To study the effect of cobalt-60 gamma-ray (⁶⁰Co-γ) radiation on the structure of Nialamide, compare the anti-inflammatory activity of irradiation products, and explore the mechanism of action. Methods After ⁶⁰Co-γ irradiation of nialamide at a dose of 50 kGy, five known compounds were obtained (2-6). The viability of RAW 264.7 (mouse mononuclear macrophage leukemia) cells treated with these compounds was determined by CCK-8 assay. The secretion of interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE₂) and the content of nitric oxide (NO) were measured using enzyme-linked immunosorbent assay and Griess method. The production of reactive oxygen species (ROS) was detected using DCFH-DA fluorescent probe. The expression levels of cell-induced nitric oxide synthase (iNOS), cyclooxygenase (COX-2), nuclear transcription factor-κB (NF-κB), and IκB were detected using Western blot. Results The products of nialamide after irradiation did not significantly affect RAW264.7 cell viability (P > 0.05) but showed a strong anti-inflammatory effect (P < 0.01). Compared with nialamide, compounds 2, 3, 4, 6 significantly reduced NO content in LPS-induced RAW 264.7 cells (P < 0.01), and compound 4 had the most significant effect. Moreover, compound 4 significantly reduced the content of IL-6, TNF-α, PGE₂, and ROS (P < 0.05) as well as the expression of iNOS, COX-2, NF-κB, and IκB (P < 0.05) in LPS-induced RAW 264.7 cells. Conclusion The chemical structure of nialamide is changed after irradiation with ⁶⁰Co-γ, and its product compound 4 shows strong anti-inflammatory activity, which may be related to inhibiting the activation of NF-κB signaling pathway and reducing the release of inflammatory factors. Radiation technology can provide new insights into the changes of molecular structures and physiological properties of natural products.

Objective To study the evaluation value of lung injury score(LIS)and advanced glycation end products(AGEs)expression levels on the prognosis of elderly patients with sepsis-related acute lung injury/acute respiratory distress syndrome(ALI/ARDS).Methods A total of 98 elderly patients with sepsis-related ALI/ARDS admitted to First Branch of the First Affiliated Hospital of Chongqing Medical University from March 2019 to April 2021 were selected as the research group,and the patients were divided into two sub-groups according to their survival within 30 d after admission:the survival group(55 cases)and the death group(43 cases).Another 51 elderly patients with non-ALI/ARDS sepsis admitted to First Branch of the First Affiliated Hospital of Chongqing Medical University in the same period were selected as the control group.After admission,the clinical data of patients were recorded,and the levels of serum creatinine,troponin I,B-type brain natriuretic peptide(BNP),serum C-reactive protein(CRP)and procalcitonin(PCT)were de-tected.Enzyme-linked immunosorbent assay was used to determine the levels of AGEs in patients'serum.The LIS score was evaluated by LIS scale.With clinical factors as independent variables and prognosis as dependent variables,Logistic regression curve was used to analyze the death factors of elderly sepsis-related ALI/ARDS patients.Results AGEs levels,LIS scores,acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)scores decreased sequentially in the death group,survival group,and control group(all P<0.05).The levels of lactic acid,blood glucose,troponin I,PCT,BNP and CRP in arterial blood of patients in the death group were significantly higher than those in the survival group and the control group(P<0.05).The results showed that arterial lactate,blood glucose,troponin I,PCT,BNP,CRP,AGEs,APACHE Ⅱ score,and LIS score were all independent risk factors for mortality in elderly sepsis-related ALI/ARDS patients(P<0.05).The area under the curve(AUC)of LIS score predicting prognosis in elderly sepsis-related ALI/ARDS pa-tients was 0.857(95%CI:0.821-0.911),and AUC of serum AGEs was 0.861(95%CI:0.809-0.908).LIS score and AGEs level had certain predictive value for the prognosis of elderly sepsis-related ALI/ARDS pa-tients.Conclusion The LIS score and AGEs level of the elderly patients with sepsis-related ALI/ARDS are independent risk factors of death,which have important predictive value for prognosis.

Post-acute pancreatitis diabetes is one of the most common distant complications of acute pancreatitis. However, its incidence has been underestimated for a long time, indicating that it has not been taken seriously by healthcare professionals in clinical practice. This article provides a review of the urgent need for healthcare professionals to focus on the current status, adverse outcomes, screening and management aspects of diabetes after acute pancreatitis, and aims to provide a reference for healthcare professionals in their relevant clinical work.

ObjectiveTo investigate the effects of maltol aluminum exposure on miR-193a-3p, demethylase AlkB homolog 5 (ALKBH5), phosphatase and tensin homolog deleted on chromosome ten (PTEN) and protein kinase B (AKT), and whether miR-193a-3p is involved in aluminum-induced cognitive impairment by regulating ALKBH5/PTEN/AKT signaling pathway. Methods Specific pathogen-free male SD rats were randomly divided into control group and low-, medium- and high- dose groups according to their body weight, with eight rats in each group. Rats in the low-, medium-, and high- dose groups were intraperitoneally injected with maltol aluminum solution at concentrations of 10.00, 20.00, and 40.00 μmol/kg body weight, respectively, while the rats in control group were given an equal volume of 0.9% sodium chloride solution. Rats were injected for five days every week for three months. After injection, the novel object recognized test was used to assess the learning and memory ability of the rats. The relative expression of miR-193a-3p and B-cell lymphocytoma-2 (Bcl-2), Bcl-2 associated X protein (Bax) and cysteine aspartate protease-3 (Caspase-3) mRNA in rat hippocampus was detected using the real-time quantitative polymerase chain reaction. The relative protein expression of ALKBH5, PTEN, and AKT2 in the rat hippocampus was detected using Western blot. Results The discrimination index and the preference index of the new object recognition test of the rats in high-dose group were lower than those in control group and low-dose group (all P<0.05). The relative expression of miR-193a-3p and Bcl-2 mRNA in the hippocampus of the rats in high-dose group was lower than those in control group and low-dose group (all P<0.05). The relative mRNA expression of Bax in the high-dose group was higher than those in the control group and low-dose group (both P<0.05). The relative mRNA expression of Caspase-3 of the rats in the high-dose group was higher than that in the other three groups (both P<0.05). The relative protein expression of ALKBH5 in the hippocampus of the rats in the high-dose group was lower than that in the control group (P<0.05). The relative expression of PTEN protein was higher than those in the control group and low-dose group (both P<0.05). The relative protein expression of AKT2 was lower than those in the control group and low-dose group (both P<0.05). Conclusion Sub-chronic aluminum exposure can inhibit the expression of miR-193a-3p in the hippocampus of rats, which may disrupt the ALKBH5/PTEN/AKT pathway and affect normal neuronal homeostasis and cellular function. This pathway may play an important role in aluminum-induced cognitive impairment.

Objective To analyze the changes in the disease spectrum of hospitalized patients with neurological diseases in a tertiary hospital in the past 5 years,in order to effectively develop targeted disease prevention and treatment strategies.Methods Collect case data of neurological diseases in a tertiary hospital from January 1,2018 to December 31,2022,and use ICD-10 coding for disease classification,and analyze the disease type,gender,age groups,and other factors.Results A total of 9060 patients with neurological diseases were admitted in the past five years.In 2020,the number of discharged patients affected by the COVID-19 was the smallest,accounting for 15.96% ,and in 2022,the number was the largest,accounting for 24.05% .The number of cases showed an increasing trend.There was no statistically significant difference in the composition of male and female patients;There is a statistically significant difference in the number of cases among patients of different age groups,and the incidence categories are different;The top 10 diseases in the ranking of neurological diseases are:transient ischemic attack,headache,spinal nerve disease,neurological disorders,epilepsy,Parkinson's disease,sleep disorders,paralysis,other brain diseases,hydrocephalus.The distribution of the top 10 diseases by gender has statistical significance.Conclusion The hospital can formulate the diagnosis and treatment technology for different age groups according to the distribution characteristics of disease spectrum,carry out comprehensive prevention and treatment measures for key groups,strengthen the construction of key special-ties and allocate health resources properly.

Objective:To investigate the prevalence of adult skeletal fluorosis caused by drinking tea-type endemic fluorosis in Yushu Tibetan Autonomous Prefecture (hereinafter referred to as Yushu Prefecture), Qinghai Province, and provide scientific basis for prevention and control of the disease.Methods:In August 2021, one village was selected as a survey site in six counties (cities) in Yushu Prefecture, including Nangqian, Chindu, Yushu, Zadoi, Qumarlêb, and Zhiduo. Drinking water samples and 10 brick tea samples were collected from each village to determine the fluoride content in water and brick tea; at least 100 permanent residents aged ≥ 25, who had a habit of drinking brick tea and had lived in the local area for more than 5 years, were selected for X-ray imaging to examine the prevalence of adult skeletal fluorosis.Results:A total of 75 samples of residential drinking water were collected, with a fluoride content of (0.21 ± 0.05) mg/L, ranging from 0.11 to 0.34 mg/L; 60 samples of brick tea, with a fluoride content of (626.70 ± 157.27) mg/kg, ranging from 324.00 to 2 102.00 mg/kg. A total of 1 136 adults were examined, and 318 cases of skeletal fluorosis were diagnosed, with a detection rate of 27.99%. Among them, the detection rates of mild, moderate, and severe skeletal fluorosis were 20.95% (238/1 136), 6.07% (69/1 136), and 0.97% (11/1 136), respectively, with mild symptoms being the main. The detection rates of skeletal fluorosis in males and females were 29.09% (121/416) and 27.36% (197/720), respectively, with no statistically significant difference between the gender (χ 2 = 0.39, P = 0.533). Comparison of the skeletal fluorosis in different gender, the differences were statistically significant (χ 2 = 22.31, P < 0.001). The detection rates of skeletal fluorosis in the age groups of 25 - 35, 36 - 45, 46 - 55, 56 - 65, 66 - 75, and ≥76 years old were 6.86% (7/102), 22.37% (51/228), 24.02% (92/383), 37.44% (73/195), 43.48% (70/161), and 37.31% (25/67), respectively. The differences between the groups were statistically significant (χ 2 = 59.84, P < 0.001). Moreover, there was a statistically significant difference in the composition of skeletal fluorosis among different age groups ( H = 37.66, P < 0.001). The Spearman correlation analysis results showed that the severity of adult skeletal fluorosis was positively correlated with age ( r = 0.34, P < 0.001). Conclusions:There is a certain degree of prevalence of adult skeletal fluorosis in Yushu Prefecture. And as age increases, the condition of skeletal fluorosis becomes more severe.

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.