Background Protein tyrosine phosphatase non-receptor type II (PTPN2) is essential for the regulation of inflammation and immunity, but the specific mechanism of action of Ptpn2 in silicosis is unknown. Objective To investigate the regulatory role of overexpression of Ptpn2 in SiO₂-mediated inflammatory response in alveolar type II epithelial cells based on transcriptome sequencing. Methods This study was an in vitro study. A negative control group (vector transferred) and an overexpression of Ptpn2 group of mouse lung epithelial cell line MLE-12 cells were firstly constructed. Transcriptome sequencing was performed to detect differentially expressed genes (DEGs), differentially expressed mRNAs, and differentially expressed ncRNAs in the two groups of MLE-12 cells, and then the DEGs were analyzed by the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Constructed MLE-12 cells and A549 cells were stimulated using SiO₂ suspension, and divided into a negative control group (vector transferred), an overexpression of Ptpn2 group, a negative control + SiO₂ group, and an overexpression of Ptpn2 + SiO₂ group, respectively. Protein expressions of tumor necrosis factor-α (TNF-α) and interleukin (IL)-17A, IL-2, IL-1β were detected by Western blot. Positive TNF-α expression was detected by immunofluorescence staining. Results The results of Western blot showed that the protein expression level of PTPN2 was up-regulated in the overexpressed Ptpn2 group compared with the negative control group (P < 0.05). The volcano plot and clustering heat map showed that there were 1122 DEGs, 3681 differentially expressed mRNAs, and 474 differentially expressed ncRNAs in the overexpressed Ptpn2 group compared with the negative control group. The results of GO enrichment showed that, in terms of the biological process, the DEGs were mainly related to the regulation of metal ion transport, extracellular matrix organization, and extracellular structural organization; in terms of cellular composition, the DEGs were mainly related to collagen-containing extracellular matrix, receptor complexes, and basement membranes; in terms of molecular function, the DEGs were mainly related to the extracellular matrix structural constituents, glycosaminoglycan binding, and semaphorin receptor binding. The results of KEGG enrichment showed that the DEGs were closely related to cytokin-cytokine receptor interaction, IL-17 signaling pathway, TNF signaling pathway, and chemokine signaling pathway. In MLE-12 and A549 cells, the results of Western blot showed that the protein expression levels of TNF-α , IL-17A, IL-2, and IL-1β were up-regulated in the negative control + SiO₂ group compared with the negative control group (P < 0.05), and the protein expression levels of TNF-α, IL-17A, IL-2, and IL-1β were down-regulated in the overexpression of Ptpn2 + SiO₂ group compared with the negative control + SiO₂ group (P < 0.05). The immunofluorescence staining showed that the expression of TNF-α was increased in the negative control + SiO₂ group compared with the negative control group, and decreased in the overexpression of Ptpn2 + SiO₂ group compared with the negative control + SiO₂ group. Conclusion Overexpression of Ptpn2 inhibits SiO₂-mediated inflammatory response in MLE-12 cells and A549 cells.

OBJECTIVE To improve the efficiency and quality of dispensed oral drug management in the inpatient pharmacy， and ensure the safety of drug use in patients. METHODS SWOT （strength， weakness， opportunity， threat） analysis method was used to analyze the internal strengths and weaknesses， as well as the external opportunities and threats in the construction of a closed-loop management system for dispensed oral drugs in the inpatient pharmacy of our hospital， and propose improvement strategies. RESULTS & CONCLUSIONS A refined， full-process， closed-loop traceability management system for dispensed oral drugs in the inpatient pharmacies was successfully established， which is traceable in origin， trackable in destination， and accountable in responsibility. After the application of this system， the registration rate of dispensed drug information and the correctness rate of registration content both reached 100%. The proportion of overdue drug varieties in the same period of 2024 decreased by 77.78% compared to March 2020， the inventory volume decreased by 29.50% compared to the first quarter of 2020， the per-bed medication volume decreased by 32.14% compared to the first quarter of 2020； the average workload per post in the same period of 2023 increased by 49.09% compared to 2019， the dispensing accuracy rate reached 100%， and the improvement rate of quality control problem increased by 25.25% compared to 2021. This system effectively improves the safety and accuracy of dispensed oral drug management in the inpatient pharmacy.

Background Pneumoconiosis is the most serious occupational disease in China, among which silicosis accounts for more than 50%. microRNA (miRNA) plays an important role in the occurrence process of silicosis fibrosis, but the mechanism of it has not been fully clarified yet. Objective To explore the molecular mechanism by which miR-411-3p modulates the ubiquitination degradation of SMAD specific E3 ubiquitin protein ligase (SMURF) 2/Smad7, thereby suppressing epithelial-mesenchymal transition (EMT) in mouse alveolar type II epithelial cells and counteracting silica-induced pulmonary fibrosis. Methods Twenty-four 8-week-old SPF male C57BL/6J mice were randomly divided into four groups: Control group, silica group, silica +miR-411-3p agomir-NC group, and silica +miR-411-3p agomir group, with 6 mice in each group. Silicosis model was prepared by a one-time bronchial infusion of silicon dioxide (SiO₂) (200 mg·mL^-1, 50 μL). In vitro MLE-12 cells were divided into (1) control group and SiO₂ group, (2) SiO₂+negative control siRNA (siRNA-NC) group and SiO₂+Smurf2 gene silencing (si-Smurf2) group, (3) SiO₂+solvent (DMSO) group and SiO₂+protease inhibitor (MG132) group, (4) mutant sequence plasmid (Mut)+miR-411-3p mimic control (miR-NC) group, Mut+miR-411-3p mimic group, wild sequence plasmid (Wt)+miR-NC group, and Wt+miR-411-3p mimic group, (5) SiO₂+miR-NC group and SiO₂+miR-411-3p mimic group. The pathological morphology and collagen deposition of lung tissue were observed after staining. Detection of miR-411-3p and proteins was conducted by real-time fluorescent quantitative PCR and Western blot. The binding of SMURF2 to Smad7 protein and Smad7 to ubiquitin (Ub) were detected by co-immunoprecipitation (Co-IP) method. Dual-luciferase reporter gene assay was adopted to verify the regulatory effect of miR-411-3p on Smurf2. Results In the SiO₂-induced MLE-12 cells, compared to the control group, the SiO₂-treated group showed significantly upregulated expressions of N-cadherin (N-Cad), collagen I (CoL I), SMURF2, transforming growth factor-β1 (TGF-β1), and phosphorylated Smad2/3 (p-Smad2/3). In contrast, the expressions of E-cadherin (E-Cad), Smad7, and miR-411-3p were significantly downregulated (P<0.05). The dual-luciferase reporter gene assay revealed a regulatory effect of miR-411-3p on Smurf2 (P<0.05). Meanwhile, in the MLE-12 cells induced by SiO₂, the miR-411-3p mimic down-regulated the protein expressions of SMURF2, N-Cad, CoL I, TGF-β1, and p-Smad2/3, while up-regulated the protein expressions of E-Cad and Smad7 (P<0.05). The silenced Smurf2 gene inhibited the expressions of N-Cad, CoL I, and p-Smad2/3 proteins, while promoted the expressions of E-Cad and Smad7 proteins in the MLE-12 cells (P<0.05). The Co-IP results showed that the binding of SMURF2 to Smad7 was enhanced, and the ubiquitin binding ability of Smad7 was enhanced in the SiO₂ group. In the lung tissue of mice, the results of pathological observation with hematoxylin-eosin (HE) and sirius red (VG) staining showed that compared with the agomir-NC, the lesion was relieved in the lung tissue of the miR-411-3p agomir group. Meanwhile, the expressions of SMURF2, N-Cad, CoL I, TGF-β1, and p-Smad2/3 were significantly down-regulated, while the expressions of E-Cad and Smad7 were significantly up-regulated (P<0.05). Conclusion MiR-411-3p alleviates the EMT of alveolar type II epithelial cells and antagonizes silicosis fibrosis progression in mice by inhibiting SMURF2-mediated ubiquitination and degradation of Smad7.

ObjectiveTo observe the effect of modified Tianwang Buxindan （MTBD） on the skin of sleep-deprived （SD） mice and investigate its mechanism. MethodSixty 2-month-old female Kunming mice were randomly divided into a blank group， a model group， a vitamin C （VC， 0.08 g·kg^-1）， and MTBD low-， medium-， and high-dose groups （6.5， 12.5， 25 g·kg^-1）. Except for the blank group， the other groups were subjected to SD mouse model induction （using multiple platform water environment method for 18 hours of sleep deprivation daily from 15：00 to next day 9：00）， continuously for 14 days， and caffeine （CAF， 7.5 mg·kg^-1） was injected intraperitoneally from the 2nd week onwards， continuously for 7 days. While modeling， the blank group and the model group were administered with normal saline （0.01 mL·g^-1）， and the other groups received corresponding drugs for treatment. On the day of the experiment， general observations were recorded （such as body weight， spirit， fur， and skin）. After sampling， skin tissue pathological changes were observed under an optical microscope using hematoxylin-eosin （HE） and Masson staining methods. Skin thickness and skin moisture content were measured. Biochemical assay kits were used to detect skin hydroxyproline （HYP） content， skin and serum superoxide dismutase （SOD） activity， and malondialdehyde （MDA） content. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum interleukin （IL）-6， tumor necrosis factor （TNF）-α， and IL-1β levels in mice. Western blot was used to detect skin tissue type Ⅰ collagen （ColⅠ）， type Ⅲ collagen （ColⅢ）， phosphatidylinositol 3-kinase （PI3K）， phosphorylated （p）-PI3K， protein kinase B （Akt）， p-Akt， nuclear factor E₂-related factor 2 （Nrf2）， heme oxygenase （HO）-1， and nuclear factor （NF）-κB protein expression. ResultCompared with the blank group， the model group showed varying degrees of changes. In general， signs of aging such as reduced body weight （P<0.01）， listlessness， dull fur color， and formation of wrinkles on the skin appeared. Tissue specimen testing revealed skin thinning， flattening of the dermoepidermal junction （DEJ）， and reduced collagen fibers under the optical microscope. Skin thickness and moisture content decreased， skin tissue HYP content significantly decreased （P<0.01）， skin and serum SOD activity significantly decreased （P<0.01）， and MDA content significantly increased （P<0.01）. Serum IL-6， TNF-α， and IL-1β levels significantly increased （P<0.01）. Skin ColⅠ， ColⅢ， p-PI3K/PI3K， p-Akt/Akt， Nrf2， and HO-1 protein expression significantly decreased （P<0.05， P<0.01）， and NF-κB expression increased （P<0.01）. Compared with the model group， the VC group and the MTBD low-dose group showed increased skin moisture content， HYP content， SOD activity， and ColⅠ， ColⅢ， p-PI3K/PI3K protein expression （P<0.05， P<0.01）， and decreased serum MDA content （P<0.05）. In addition， a decrease in serum IL-6 and IL-1β levels was detected in the MTBD low-dose group （P<0.05）， while the above indicators in the MTBD medium- and high-dose groups improved （P<0.05， P<0.01）. ConclusionSleep deprivation accelerates the aging process of the skin in SD model mice. MTBD can improve this phenomenon， exerting anti-inflammatory and antioxidant effects， and its mechanism of action may be related to the activation of the PI3K/Akt/Nrf2 signaling pathway.

Background The senescence of alveolar type II epithelial cells is an important driving factor for the progression of silicotic fibrosis, and the regulatory effects of oxamate on the senescence of alveolar type II epithelial cells is still unclear. Objective To explore whether lactate dehydrogenase inhibitor oxamate can alleviate silicotic fibrosis in mice by inhibiting senescence of alveolar type II epithelial cellsMethods This study was divided into two parts: in vivo experiments and in vitro experiments. In the first part, forty SPF C57BL/6J male mice were randomly divided into four groups with 10 in each group: control group, silicosis model group, low-dose oxamate treatment group, and high-dose oxamate treatment group. The silicotic mouse model was established by intratracheal instillation of 50 μL SiO₂ suspension (100 mg·mL⁻¹). The treatment models were prepared by intraperitoneal injection of 100 μL oxamate (225 mmol·L⁻¹ and 1125 mmol·L⁻¹). In the second part, induction of MLE-12 mouse alveolar type II epithelial cells was conducted with SiO₂. The in vitro experimental groups were ① SiO₂ induction groups: control group, 50 μg·mL⁻¹ SiO₂ group, 100 μg·mL⁻¹ SiO₂ group, and 200 μg·mL⁻¹ SiO₂ group, and ② oxamate treatment groups: control group, SiO₂ group (100 μg·mL⁻¹), low-dose oxamate (25 mmol·L⁻¹) treatment group, and high-dose oxamate (50 mmol·L⁻¹) treatment group. Pathological morphology of lung tissues was evaluated after hematoxylin-eosin (HE) staining; deposition of collagen in lung tissues was evaluated after sirius red staining; positive co-expression of prosurfactant protein C (Pro-SPC) and β-galactosidase was detected by immunofluorescence staining; positive expression of β-galactosidase in MLE-12 cells was detected by immunofluorescence staining. The protein expression levels of collagen type I (CoL I), fibronectin1 (FN1), hexokinase 2 (HK2), pyruvate kinase isozyme type M2 (PKM2), lactate dehydrogenase A (LDHA), p-ataxia telangiectasia and Rad3-related kinase (ATR), and cyclin-dependent kinase inhibitors p21, and p16 were detected by Western blotting. Results Compared with the control group, the protein expression levels of HK2, PKM2, LDHA, p-ATR, p21, and p16 were significantly upregulated in the silicosis model group and the SiO₂-induced MLE-12 cells (P＜0.05). The in vivo studies showed that, compared with the control group, the silicon nodule area, the collagen deposition area, the proportion of β-galactosidase positive cells, and the protein expression levels of CoL I, FN1, LDHA, p-ATR, p21, and p16 were significantly upregulated in the silicosis model group (P＜0.05). Compared with the silicosis model group, the oxamate treatment groups showed significant downregulation of the silicon nodule area, the collagen deposition area, the proportion of β-galactosidase positive cells, and the the CoL I, FN1, LDHA, p-ATR, p21, and p16 protein expression levels, and the high-dose oxamate treatment group showed a higher efficacy on these indicators than the low-dose oxamate treatment group (P＜0.05). The in vitro studies showed that, compared with the control group, the proportion of β-galactosidase positive cells and the protein expression levels of p-ATR, p21, and p16 were significantly upregulated in the SiO₂-induced group (P＜0.05). Compared with the SiO₂ group, the proportion of β-galactosidase positive cells and the LDHA, p-ATR, p21 and p16 protein expression levels were significantly downregulated in the oxamate treatment groups, and the high-dose oxamate treatment group showed a higher efficacy on these indicators than the low-dose oxamate treatment group (P＜0.05). Conclusion Lactate dehydrogenase inhibitor oxamate can alleviate silicotic fibrosis in mice by inhibiting the senescence of alveolar type II epithelial cells.

Objective To investigate the classification,clinical manifestations,diagnosis,differential diagnosis and treatment of oral lichenoid lesions and provide a reference for clinical practice.Methods Hospital ethical approval and patient informed consent were obtained.We report a case of oral lichenoid lesion in children and review the diagno-sis and treatment of oral lichenoid damage in the literature.Results The patient experienced repeated rupture of the dorsal surface of the tongue with pain for more than 3 years.There was a large area of tongue back surface erosion with an irregular shape,surrounded by pearly-white lines.The left erosive area was accompanied by tissue hyperplasia,which was approximately 1.5 cm × 2.0 cm,with tough texture and broad masses.The pathological diagnosis of the pa-tient was oral lichenoid lesion.After biopsy of the dorsal surface of the tongue,the pathological diagnosis of the patient was granulomatous inflammation.The final diagnosis of lichenoid granulomatous stomatitis was made on the basis of the patient's intraoral damage features,systemic history,medication history and histopathological findings.A review of the literature suggests that oral lichenoid lesions have an unknown etiology and need to be clinically differentiated from oral lichen planus,oral lichenoid drug reactions,oral lichenoid contact damage and chronic ulcerative stomatitis.The clini-cal treatment of oral lichen planus is based on the topical and/or systemic use of glucocorticoids.Conclusion There are still no uniform criteria for the classification and diagnosis of oral lichenoid lesions.They rely mainly on history tak-ing,clinical manifestations and histopathological findings,and the treatment is mainly based on the topical and/or sys-temic use of glucocorticoids.

Objective: To explore the emotional and behavioral problems of different only child and multiple child families, and to provide a reference for developing effective parenting styles. Methods: A stratified random cluster sampling method was adopted to investigate 2 647 guardians of preschool children in Tongling City from April to June, 2022. Children s emotional and behavioral problems were evaluated by using the self designed parenting questionnaire and the Children s Strengths and Difficulties Questionnaire (SDQ) parent edition. Results: The abnormal total score detection rate of emotional and behavioral problems of preschool children was 15.5%, and the rate of abnormal peer interaction was the highest (19.5%). In multiple child families, the first born child (17.5%, 20.4%), compared with the second and third child (11.5%, 9.5%), was more likely to exhibit conduct and hyperactivity problems ( χ 2=8.44, 29.75, P <0.01). There were differences in parenting attitudes between only child and multiple child families( χ 2=9.38, P <0.05). The results of the Logistic regression analysis showed that more frequent parent child discussion, the persuasive education and consistent family discipline strategy were negatively related to the emotional and behavioral problems of only children and children in multiple child families ( OR =0.15, 0.49, 0.38; 0.34, 0.40, 0.42, P <0.05). However, harmonious family relationships were only negatively related to emotional and behavioral problems in only children ( OR =0.08, P <0.01), and a higher education level among mothers was negatively related to emotional and behavioral problems in children from multiple child family environments( OR=0.30, 0.45, P <0.05). Conclusion The emotional and behavioral problems are serious of preschool children in Tongling City, the psychological development of the oldest children from multiple child and only child families should be actively followed, as this would help to promote a better understanding of the development of preschool children s physical and mental health.

Objective:To explore the effect of key amino acid mutations of 3D protein in enterovirus 71 on viral proliferation, and infer the mechanism of mutation affecting viral proliferation according to the tertiary structure model of 3D protein.Methods:The proliferation characteristics of the mutant strain that was constructed by site-directed mutagenesis and reverse genetics using the pMD19T-SDLY107-EGFP constructed from the fatal strain SDLY107 as a template were measured. Meanwhile the tertiary structure of the 3D protein was predicted, and then the possible mechanism of the mutation affecting the proliferation ability of the virus was speculated according to the functional characteristics of the domain of the 3D protein.Results:Two mutant viruses, eGFP-EV-A71 (S37N) and eGFP-EV-A71 (R142K), were successfully constructed by double enzyme digestion and viral gene sequencing. The proliferation rate of the two mutant strains in RD cells was significantly lower than that of the parent strains. The 3D protein tertiary structure prediction model showed that the 3D protein consisted of three domains: "Finger" , "thumb" and "Palm" , constituting a cupped right-handed structure. S37N and R142K are located in the "thumb" domain and " finger" domain, respectively. The "thumb" and "finger" domains have important effects on the activity of 3D polymerase and the stability of protein.Conclusions:Mutations at S37N and R142K sites of EV71 3D protein decrease the replication ability of EV71, and these two mutations may affect the proliferation of EV71 virus by changing the 3D protein polymerase activity and the interactions between multiple domains.

Objective:To analyze the risk factors and human papillomavirus (HPV) genotypes distribution in patients with condyloma acuminatum (CA) in two regions of Shandong province.Methods:From August 2019 to December 2020, an anonymous questionnaire survey of CA patients was conducted in three hospitals in Jinan City and Jining City, Shandong Province, and samples were collected for HPV typing. Multivariate binary logistic regression was used to analyze the risk factors of CA recurrence. HPV typing was detected by PCR-reverse dot blot hybridization.Results:A total of 653 questionnaires were collected, and the valid questionnaires accounted for 98.77% (645/653). Recurrence of the disease occurred in 174 patients, with a recurrence rate of 26.98%. Univariate analysis showed that there were statistically significant differences in the distribution of CA recurrence among residence time at current address, sexual frequency, genitalia cleaning, and knowledge of preventing HPV infection ( P<0.05). Multivariate binary logistic regression showed that knowing how to prevent HPV infection was a significant factor that influences CA recurrence. A total of 428 patients underwent HPV typing, and the positive detection rate of HPV was 98.60% (422/428). The top three positive rates were HPV6 (57.58%), HPV11 (36.49%) and HPV16 (11.37%). The main type of infection was low-risk HPV, accounting for 51.42% (217/422). Conclusions:CA patients have the phenomenon of "separation of knowledge and action" , so it is necessary to strengthen health education and behavioral intervention, guide the population to correctly treat sexual behavior, and improve self-prevention awareness and risk awareness.

Objective:We try to screen out predictive indicators with higher value by analyzing the differences in clinical and laboratory indicators between severe fever with thrombocytopenia syndrome (SFTS) patients in the intensive care unit (ICU) group and non-ICU group.Methods:The clinical and laboratory index data of 69 SFTS patients diagnosed in the laboratory in a hospital from June to December 2019 were retrospectively collected. According to the clinical outcome of the patients, they were divided into ICU and non-ICU groups. The differences in clinical manifestations and laboratory indicators between the two groups were analyzed. The receiver operating characteristic curve (ROC) was used to screen the more valuable predictive indicators.Results:Compared with the non-ICU group, ICU group SFTS patients had significantly higher procalcitonin (PCT), C-reactive protein (CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), glutamyl transpeptidase (GGT), leucine aminopeptidase (LAP), glutamate dehydrogenase (GDH), adenosine deaminase (ADA), cystatin C (Cys C), α-hydroxybutyrate dehydrogenase (α-HBDH), creatine kinase (CK), lactate dehydrogenase (LDH) levels ( W=530.0, P=0.003; W=496.5, P=0.015; W=496.0, P=0.015; W=535.5, P=0.002; W=545.5, P=0.001; W=498.5, P=0.013; W=537.0, P=0.002; W=523.0, P=0.004; W=512.0, P=0.007; W=502.0, P=0.012; W=486.0, P=0.023; W=509.0, P=0.008; W=541.0, P=0.002) and significantly lower platelet count (PLT), indirect bilirubin (IBIL), albumin/globulin ratio(A/G) and superoxide dismutase (SOD) levels ( W=199.0, P=0.024; W=175.5.5, P=0.009; t=-2.9, P=0.004; W=209.5, P=0.036; t=-3.0, P=0.004). ROC result showed that ALP [area under the curve (AUC)=0.804, 95% confidence interval ( CI) (0.679~0.929)] and LDH [AUC=0.805, 95% CI (0.680~ 0.930)] have a higher value for predicting the risk of severe illness. Conclusions:Abnormal liver function, heart function, and renal function indicators in SFTS patients indicate that patients are at risk of exacerbation. Among them, ALP and LDH levels have higher predictive value for risk of severe disease, suggesting that the monitoring of patients with the above symptoms should be strengthened in the clinical nursing process.