AIM: To investigate the application value of pre-treatment tear inflammatory factor levels in predicting therapeutic efficacy for dry eye patients.METHODS:Prospective controlled observational study. A total of 120 patients with dry eye(240 eyes)admitted to our hospital from November 2022 to March 2024 were included. Before dry eye treatment, the levels of inflammatory factors, including interlukin-4(IL-4), IL-6, IL-8, IL-10, IL-12, IL-13, IL-15, IL-18, IL-1β, interferon-γ(IFN-γ), tumor necrosis factor-α(TNF-α), granulocyte-colony stimulating factor(G-CSF), granulocyte-macrophage colony-stimulating factor(GM-CSF), monocyte chemoattractant protein-1(MCP-1)in the tear fluid were detected by ELISA. According to the treatment protocol in the Chinese Expert Consensus on the Treatment of Dry Eye(2020), the patients were given treatments, and the related factors affecting the treatment outcomes of dry eye patients were analyzed.RESULTS:After continuous treatment for 4 wk, all the patients completed follow-up, and they were divided into the markedly effective group(60 patients, 120 eyes)and the ineffective group(60 patients, 120 eyes)based on their therapeutic effects. The markedly effective group had significantly lower pre-treatment levels of IL-6, IL-10, IL-18, IL-1β, and TNF-α than the poor efficacy group(all P<0.05). IL-6(OR=0.994), IL-18(OR=0.998), IL-1β(OR=0.933), and TNF-α(OR=0.998)were independently associated with treatment efficacy(all P<0.05). The nomogram model yielded a C-index of 0.971(95% CI: 0.950-0.993), with calibration curves closely aligned to the ideal curve. The model demonstrated significant predictive value for early therapeutic efficacy(sensitivity=96.67%, specificity=71.67%, cutoff=208, AUC=0.866, 95% CI=0.794-0.952, P<0.001).CONCLUSION:The nomogram model constructed based on the levels of inflammatory factors in dry eye patients before treatment can well predict the treatment effect of patients.

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.

Objective To explore the five-circuit and six-qi features of birth time and onset time of children with acute lymphoblastic leukemia(ALL).Methods A total of 877 cases of children with ALL from Children's Hospital of Soochow University from June 2021 to February 2023 were collected,and their five-circuit and six-qi features of birth time and onset time were analyzed.And then the correlation of five-circuit and six-qi features of birth time and onset time with ALL was explored preliminarily,and the pathogenic characteristics of congenital factors and acquired pathogenic factors were revealed.Results(1)The children who were born in the year with the heavenly stems being bing(the 3rd of the ten heavenly stems)and ding(the 4th of the ten heavenly stems)and with the earthly branches being shen(the 8th of the twelve earthly branches)and you(the 9th of the twelve earthly branches)are prone to suffer from ALL,and the birth year of children with ALL had the five-circuit and six-qi features of the joining of guest circuit with dominant circuit being rebellious.ALL is commonly seen in the year with the heavenly stems being geng(the 7th of the ten heavenly stems)and xin(the 8th of the ten heavenly stems)and with the earthly branches being zi(the 1st of the twelve earthly branches)and chou(the 2nd of the twelve earthly branches),and the onset year of ALL in children had the five-circuit and six-qi features of the yearly circuit being gold-circuit and water-circuit,sitian-zaiquan yearly circuit qi being shaoyin monarch-fire with yangming dryness-gold,taiyin damp-earth with taiyang cold-water,and the qi-circuit assimilation relationship being celestial correspondence,same celestial correspondence,celestial correspondence in convergent year,disharmony,mildly-rebellious,and celestial restriction.Conclusion Gold-dryness and water-cold are the congenital factors and acquired pathogenic factors of ALL.The onset of ALL in children is closely related to qi insufficiency and qi stagnation of wood and fire in five-circuit and six-qi theory.

Objective To investigate necroptosis-related diagnostic biomarkers of bronchopulmo-nary dysplasia(BPD)and their relationships with the immune microenvironment through the analysis of necroptosis-related genes(NRGs)in BPD.Methods The dataset GSE32472 was downloaded from the Gene Expression Omnibus(GEO)database,and NRGs were obtained from the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway and Gene Cards databases.Differentially expressed necroptosis-related genes(DE-NRGs)were screened,and their biological functions and pathways were explored through functional enrichment analysis.Machine learning algorithms,inclu-ding least absolute shrinkage and selection operator(LASSO)and support vector machine-recursive feature elimination(SVM-RFE),were applied to screen feature genes.The Cell-type Ⅰdentification By Estimating Relative Subsets of RNA Transcripts(CIBERSORT)algorithm and the Estimation of Stromal and Immune Cells in Malignant Tumor Tissues using Expression Data(ESTIMATE)algo-rithm were used to explore the immune infiltration characteristics of BPD.Spearman correlation anal-ysis between feature genes and immune cells was performed using the"corrplot"package in R lan-guage.Results A total of 19 DE-NRGs were identified.The main biological functions and path-ways of DE-NRGs included the regulation of necroptosis and inflammatory responses.Three feature genes,namely flotillin-2(FLOT2),CASP8 and FADD-like apoptosis regulators(CFLAR),and charged multivesicular body protein 7(CHMP7),were further screened to construct a nomogram.In the validation sets GSE8586 and GSE188944,the area under the curve(AUC)values were all greater than 0.7.CIBERSORT analysis revealed that BPD group presented a higher proportion of naive B cells,neutrophils,eosinophils and resting mast cells compared to control group(P＜0.05).Meanwhile,the proportion of CD8+T cells,CD4+naive T cells,CD4+resting memory T cells,regulatory T cells,resting natural killer(NK)cells,M0 macrophages,M2 macrophages and activated dendritic cells was lower than that in the control group(P＜0.05).ESTIMATE analysis showed that the stromal score in the BPD group was higher than that in the control group,while the immune score was lower,with statistically significant differences(P＜0.05).Correlation analysis between the three feature genes and ESTIMATE scores indicated that FLOT2 and CFLAR were posi-tively correlated with the stromal score and negatively correlated with the immune score,whereas CHMP7 was positively correlated with the immune score and negatively correlated with the stromal score.Conclusion The three necroptosis-related feature genes can serve as diagnostic biomarkers for BPD-related necroptosis,with high diagnostic efficacy.They may play an important roles through immune mechanisms,providing new insights and theoretical references for the early diagnosis and immune intervention of BPD.

Objective: To construct an evaluation index system of oral health literacy for children's parents, so as to provide an index system for the evaluation of oral health literacy for children's parents in China. Methods: The evaluation index system of oral health literacy for children's parents was designed based on literature review and semi-structured interview. Experts from oral prevention and pediatric oral medicine were invited to participate in two-round Delphi consultations. The indicators were scored and screened according to the importance, and the weight determined using analytic hierarchy process. The effectiveness of the consultation was evaluated by positive coefficient, authority coefficient and coordination coefficient. Results: Twenty-four experts participated in the consultation, including 6 males and 18 females. There were 21 experts with a master degree, 3 experts with a doctor degree, and 20 experts with vice senior professional titles and above. The recovery rates of the two rounds of consultations were 96.00% and 100.00%, the authority coefficients were 0.866 and 0.917, the Kendall's coefficient of concordance were 0.120 and 0.156 (both P<0.05), and the coefficient of variation was 0.15-0.38 and 0.03-0.17, respectively. The final evaluation index system included 3 primary indicators, 11 secondary indicators and 40 tertiary indicators. The primary indicators were basic knowledge and concepts related to oral health, promoting lifestyle and behaviors related to oral health, and maintaining basic skills related to oral health. Conclusion The evaluation index system of oral health literacy for children's parents has been established in this study and needs to be further applied and evaluated.

Objective:To study the protective effects and mechanism of Melastoma sanguineum Sims fruit extract (MSE) on chronic chemical liver injury induced by ethanol, acetaminophen and carbon tetrachloride in mice; To discuss it mechanism.Methods:Totally 96 mice were divided into normal control group, ethanol model group, ethanol+bifendate control group and ethanol+MSE high-, medium- and low-dosage groups, APAP model group, APAP+bifendate control group and APAP+MSE high-, medium- and low-dosage groups, CCl 4 model group, CCl 4+bifendate control group and CCl 4+MSE high-, medium- and low-dosage groups, with 6 mice in each group. Except for the normal control group, the other groups were respectively prepared for the ethanol model, the APAP model and the CCl 4 model. The mice in the MSE high-, medium- and low-dosage groups were intragastrically administrated with 10, 5 and 2.5 g/kg of MSE, respectively; the bifendate control group was intraperitoneally injected with 15 mg/ml bifendate solution at 75 mg/kg; the normal control group was intraperitoneally injected with equal volume of normal saline/peanut oil solution once a day for 25 consecutive days. The levels of GPT, GOT and total bilirubin (TBIL) in serum were detected; the activities of SOD and GSH-Px and the content of MDA in liver tissue were detected; the mRNA expressions of TNF-α, IL-6, alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) were detected by qRT-PCR; the protein expressions of cytochrome P450 CYP1A1, CYP1A2, and CYP3A in liver tissue were detected by Western blot; the pathological changes of the liver tissue were observed by HE staining. Results:Compared with the corresponding ethanol, APAP and CCl 4 model groups, the serum GPT, GOT and TBIL levels of mice in the ethanol+bifendate control group and ethanol+MSE high- and medium-dosage groups, the APAP+bifendate control group and APAP+MSE high- and medium-dosage groups, and the CCl 4+bifendate control group and CCl 4+MSE high- and medium-dosage groups decreased ( P<0.01 or P<0.05), the activities of SOD and GSH-Px in the liver tissue increased ( P<0.01 or P<0.05), and the MDA level decreased ( P<0.01 or P<0.05), and the mRNA levels of IL-6 and TNF-α decreased ( P<0.01); the mRNA levels of ADH and ALDH in the ethanol+MSE high-, medium-, and low-dosage groups decreased ( P<0.01). Compared with the APAP model group, the expressions of CYP1A1 and CYP1A2 in the APAP+MSE groups increased ( P<0.01), and the expression of CYP3A protein decreased ( P<0.05); compared with the CCl 4 model group, the expressions of CYP1A1, CYP1A2 and CYP3A proteins in the CCl 4+MSE groups decreased ( P<0.05). Conclusion:MSE has a protective effect on chronic chemically-induced liver injury induced by ethanol, APAP, and CCl 4 in mice, and its mechanism may be related to antioxidant stress, inhibition of inflammatory response, and regulation of the expression of cytochrome P450-related enzymes.

Progesterone is currently the first-line drug for clinical treatment and prevention of threatened abortion and habitual abortion. However， due to its special chemical structure， its solubility is low， which limits its clinical application. Therefore， the new technology and new dosage form of progesterone solubilization preparation is an important direction of its research and development. In this paper， the research progress of progesterone solubilization preparation technology in recent years is reviewed. It is found that the water solubility of progesterone can be enhanced by solid dispersion technology， inclusion technology， micronization， nanocrystallization （ including nanosuspensions， polymer micelles， nanoparticles， etc. ）， liposome technology， self- emulsification， cocrystal technology， and 3D printing. Eight technologies are used to increase the solubility of progesterone， improve its bioavailability and reduce its toxic and side effects， to serve the clinic better.

ObjectiveTo investigate the possible mechanism of Buzhong Yulin Decoction （补中愈淋汤） in the prevention and treatment of recurrent urinary tract infection. MethodsThe mouse models of recurrent urinary tract infection were established by uropathogenic Escherichia coli （UPEC） strain UTI89 by bladder perfusion， and the successful mouse models were randomly divided into a model group， an antibiotic group， and a low- and high-dose Buzhong Yulin Decoction group， with six mice in each group. In addition， 5 C57BL/6 mice without modelling were taken as blank group. The low- and high-dose Buzhong Yulin Decoction groups received 0.1 ml/10 g of decoction by gavage， with concentrations of 1.3 g/ml and 5.2 g/ml， respectively； the antibiotic group received 0.1 ml/10 g of levofloxacin hydrochloride solution with 5 mg/ml by gavage； the blank and model groups received 0.1 ml/10 g of distilled water by gavage. Each group was gavaged once a day for 7 consecutive days. The total number of urine marks， the number of central urine marks， and the total urine volume of the urine marks were observed by the urine marking test； HE staining was used to observe the histopathological changes in the bladder of mice； serum levels of the inflammatory factors interleukin 1β （IL-1β）， interleukin 6 （IL-6） and tumour necrosis factor α （TNF-α） were detected by ELISA； the morphology of the epithelial cells of bladder was observed by scanning electron microscopy； immunofluorescence assay to detect bladder tissue anti-UroPlakin 3A protein level and UPEC bacterial load； the spread plate method to detect urinary bacterial load and bacterial load of bladder epithelial cells； RT-PCR method to detect Ras-related protein Rab-11A （RAB11A） and Ras-related protein Rab-27B （RAB27B） mRNA level in bladder tissue； immunoblotting to detect microtubule-associated protein 1 light chain3 （LC3） and P62 protein levels in bladder tissue. ResultsCompared with the blank group， the bladder epithelial cell layers were lost and showed abnormal morphology in mice of the model group； bladder tissue UroPlakin 3A protein and RAB11A and RAB27B mRNA levels reduced， the total number of urine marks， the number of central urine marks， bladder tissue UPEC bacterial load， urinary bacterial load， bacterial load in bladder epithelial cells， serum IL-1β， IL-6， and TNF-α levels， and LC3 and P62 protein levels in bladder tissue all elevated （P＜0.05 or P＜0.01）. Compared with the model group， the bladder epithelial cell layers were intact and the morphology of epithelial cells were regular in the low- and high-dose Buzhong Yulin Decoction groups； the average surface area of bladder epithelial cells reduced， the levels of UroPlakin 3A protein and RAB11A and RAB27B mRNA in bladder tissues elevated， and total number of urine marks， the number of central urine marks， bladder tissue UPEC bacterial load， urinary bacterial load， bacterial load in bladder epithelial cells， serum IL-1β， IL-6， and TNF-α levels， and P62 protein levels in bladder tissue all reduced （P＜0.05 or P＜0.01）， but LC3 protein levels showed no statistically significant （P＞0.05）. In the antibiotic group， the bladder epithelial cells were partially missing and the morphology of epithelial cells was abnormal. Compared with the antibiotic group， the average surface area of the bladder epithelial cells in the mice increased in the low- and high-dose Buzhong Yulin Decoction groups， the bacterial load of the bladder epithelial cells decreased， and the P62 protein level of the bladder tissue decreased （P＜0.05）. When comparing between the low- and high-dose Buzhong Yulin Decoction groups， the differences in each index were not statistically significant （P＞0.05）. ConclusionBuzhong Yulin Decoction may prevent and treat recurrent urinary tract infection by repairing the bladder mucosal barrier， increasing RAB11A and RAB27B level and enhancing autophagy in bladder tissues， thereby facilitating bacterial clearance from bladder epithelial cells and reducing the bacterial load of bladder epithelial cells.

Radiation-induced injury, a body dysfunction caused by irradiation, is associated with the dose, duration, and speed of radiation and is predominantly derived from radiation therapy for patients with malignant tumors. The current clinical treatment mainly includes amelioration of injury, alleviation of symptoms, and improvements in function restoration of the affected sites because of lack of targeted agents specific to radiation-induced injuries. Research and development of preventive and therapeutic agents against radiation-induced injuries are of great significance to reduce the body damages caused by radiotherapy and improve the quality of life of cancer survivors. This review summarizes the radiation-induced injury and its mechanisms, radioprotectants, and therapeutic agents for radiation, and proposes future development directions, so as to provide a reference for alleviation of radiation-induced injury and improvement in prognosis.

Objective:To investigate the feasibility and clinical diagnostic value of rapid arterial spin labeling (ASL) imaging in brain glioma.Methods:Patients with glioma admitted to Beijing Tiantan Hospital, Capital Medical University from May 2021 to December 2022 were prospectively enrolled. All patients received MR rapid ASL (scan time: 1 min) and conventional ASL (scan time: 4 min 30 s), where the cerebral blood flow (CBF) perfusion maps were obtained. The qualitative analysis of CBF signal intensity and quantitative analysis of average CBF values from both tumor solid and edema regions were conducted by two radiologists independently. Kappa test and intraclass correlation coefficient ( ICC) were used to analyze the consistency of qualitative and quantitative results, respectively. Results:A total of 30 patients with brain glioma were included. The 2 physicians used rapid ASL to determine low perfusion, isoperfusion, and hyperperfusion in the tumor area in 1, 6, 23 cases and 0, 5, and 25 cases, respectively; and used conventional ASL to determine low perfusion, isoperfusion, and hyperperfusion in the tumor area in 0, 9, and 21 cases, respectively. The results of qualitative analysis of rapid ASL and conventional ASL were highly consistent within and between groups ( Kappa was 0.830 and 0.850 respectively). The results of quantitative analysis of rapid ASL and conventional ASL were highly consistent within and between groups ( ICC 0.940—0.994). Conclusion:Rapid ASL with shorter scanning time could be applied in assessing tissue perfusion in brain glioma and contribute to the clinical diagnosis of gliomas.