BACKGROUND:Macrophage migration inhibitory factor(MIF)is a pleiotropic cytokine,which is secreted in different types of stem cells and can regulate the proliferation,differentiation and migration of various types of stem cells.Our previous research has confirmed that human embryonic stem cells secrete MIF and that its concentration in the culture medium is relatively stable.However,whether MIF is involved in the survival,proliferation and differentiation of human embryonic stem cells remains unclear. OBJECTIVE:To investigate the effects of MIF on survival,proliferation,and differentiation of human embryonic stem cells. METHODS:(1)Human embryonic stem cells H9 were cultured.The growth curve of cells was detected and plotted by CCK-8 assay.Enzyme-linked immunosorbent assay was used to determine the level of MIF in the medium.(2)To determine the effects of exogenous MIF on the survival and proliferation of human embryonic stem cells,different groups were established:the control group,which was cultured in stem cell medium without any modifications;the exogenous MIF group,which was treated with different concentrations(30,100,300 ng/mL)of MIF in the stem cell medium;the MIF inhibitor ISO-1 group,which was treated with different concentrations(2,7,21 μmol/L)of ISO-1 in the stem cell medium;and the MIF+ISO-1 group,which was treated with different concentrations of ISO-1 along with 100 ng/mL of MIF.Cell viability was assessed using the CCK-8 assay.(3)To further elucidate the effect of MIF gene on survival and proliferation of human embryonic stem cell,the MIF knockout H9 cell line was constructed by CRISPR-Cas 9 technology to observe the lineage establishment.(4)To determine the effect of high concentrations of MIF on human embryonic stem cell differentiation,100 ng/mL MIF and 100 ng/mL of CXCR4 neutralizing antibody were separately added to the normal stem cell culture medium.The expression levels of self-renewal factors(KLF4,c-MYC,NANOG,OCT4,and SOX2)and differentiation transcription factors(FOXA2,OTX2)were measured using real-time quantitative polymerase chain reaction,immunofluorescence staining,and western blot analysis. RESULTS AND CONCLUSION:(1)The logarithmic growth phase of H9 cells was between 3-6 days.Under normal growth conditions,human embryonic stem cells secreted MIF at a concentration of approximately 20 ng/mL,independent of cell quantity.(2)Compared to the control group,the addition of different concentrations of MIF had no effect on the proliferation of human embryonic stem cells(P>0.05).ISO-1 significantly inhibited the proliferation of human embryonic stem cells,with a stronger inhibition observed at higher concentrations of ISO-1(P<0.05).The addition of MIF in the presence of ISO-1 reduced the inhibitory effect of ISO-1(P<0.05).(3)Real-time quantitative polymerase chain reaction showed that knocking out 50%of the MIF gene resulted in a significant decrease in the growth vitality of human embryonic stem cells and failure to establish cell lines.(4)Adding 100 ng/mL exogenous MIF to the culture medium resulted in a decrease in the mRNA,protein,and fluorescence expression levels of the self-renewal transcription factor KLF4,while the mRNA,protein,and fluorescence expression levels of the differentiation factor FOXA2 increased.(5)When 100 ng/mL CXCR4 neutralizing antibody was added to the culture medium,the mRNA and protein expression levels of KLF4 increased,while the mRNA and protein expression levels of FOXA2 decreased,contrary to the expression trend observed in the MIF group.In conclusion,the endogenous secretion of MIF by human embryonic stem cells is essential for their survival.The addition of MIF to the culture medium does not promote the proliferation of human embryonic stem cells.However,it can lead to a decrease in the expression of the self-renewal factor KLF4 and an increase in the expression of the transcription factor FOXA2.This provides a clue for further investigation into the effects and mechanisms of MIF on the differentiation of human embryonic stem cells.The MIF-CXCR4 axis plays a regulatory role in this process.

Objective: To investigate the trends in disease burden due to childhood asthma in China from 1990 to 2021 and to project the disease burden from 2022 to 2035, so as to provide insights into formulation of the control interventions for childhood asthma in China. Methods: The prevalent case, agestandard prevalence, disability-adjusted life years (DALYs) and agestandard DALYs rate of children with asthma at ages of 0 to 14 years and their 95% uncertainty interval (UI) in China from 1990 to 2021 were extracted from the Global Burden of Disease (GBD) database. The temporal trends in the disease burden of childhood asthma were evaluated with estimated annual percentage change (EAPC) and its 95% confidence interval (CI), and the disease burden due to asthma was projected among children at ages of 0 to 14 years in China using a Bayesian age-period-cohort (BAPC) model from 2022 to 2035. Results: There were 9.368 3 million (95%UI=6.410 7 million to 14.026 1 million) prevalent cases of asthma among children at ages of 0 to 14 years in China in 2021, contributing to 0.387 9 million (95%UI=0.216 1 million to 0.668 8 million) DALYs loss. The prevalent cases and DALYs of asthma decreased by 37.28% and 52.55% among children at ages of 0 to 14 years in China in 2021 compared with 1990, and the agestandardized prevalence [EAPC=-0.70%, 95%CI=-1.26% to -0.13%)] and DALY rates [EAPC=-1.71%, 95%CI=-2.32% to -1.10%)] also appeared a tendency towards a decline. From 1990 to 2021, the prevalent cases, prevalence, DALYs and DALYs rate of asthma were all higher among male children than among female children, and the disease burden of asthma was higher among children at ages of 5 to 9 years than at other age groups. BAPC model predicted a decline in both prevalent cases and DALYs of asthma among children at ages of 0 to 14 years in China from 2022 to 2035, with 6.759 6 million prevalent cases and DALYs of 0.228 4 million personyears in 2035, while the prevalence and DALYs rates were projected to rise to 5 143.35/105 and 173.75/105 in 2035. Conclusions Despite a reduction in the disease burden of asthma among children at ages of 0 to 14 years in China from 1990 to 2021, the prevalence remained high. The disease burden due to asthma is projected to appear a decline among children at ages of 0 to 14 years in China from 2022 to 2035; however, the prevalence and DALYs rates still rise. Intensified control measures and targeted interventions are required to reduce the disease burden of childhood asthma.

[Objective] To explore the strategy of blood management in patients with massive transfusion in the frigid plateau region. [Methods] The treatment process of a patient with liver rupture in the frigid plateau region was analyzed, and the blood management strategy of the frigid plateau region was discussed in combination with the difficulties of blood transfusion and literature review. [Results] The preoperative complete blood count (CBC) test results of the patient were as follows: RBC 3.14×10¹²/L, Hb 10⁶ g/L, HCT 30.40%, PLT 115.00×10⁹/L; coagulation function: PT 18.9 s, FiB 1.31 g/L, DD > 6 μg/mL, FDP 25.86 μg/mL; ultrasound examination and imaging manifestations suggested liver contusion and laceration / intraparenchymal hematoma, splenic contusion and laceration, and massive blood accumulation in the abdominal cavity; it was estimated that the patient's blood loss was ≥ 2 000 mL, and massive blood transfusion was required during the operation; red blood cell components were timely transfused during the operation, and the blood component transfusion was guided according to the patient's CBC and coagulation function test results, providing strong support and guarantee for the successful treatment of the patient. The patient recovered well after the operation, and the CBC test results were as follows: RBC 4.32×10¹²/L, Hb 144 g/L, HCT 39.50%, PLT 329.00×10⁹/L; coagulation function: APTT 29.3 s, PT 12.1 s, FiB 2.728 g/L, DD>6 μg/mL, FDP 25.86 μg/mL. The patient was discharged after 20 days, and regular follow-up reexamination showed no abnormal results. [Conclusion] Individualized blood management strategy should comprehensively consider the patient’s clinical symptoms, the degree of hemoglobin decline, dynamic coagulation test results and existing treatment conditions. Efficient and reasonable patient blood management strategies can effectively improve the clinical outcomes of massive transfusion patients in the frigid plateau region.

AIM: To investigate the protective effect of β-sitosterol on retinal structure and function and its underlying molecular mechanism in a sodium iodate(NaIO3)-induced mouse model of dry age-related macular degeneration(ARMD).METHODS: A dry ARMD mouse model was established by NaIO3 injection. The therapeutic effect of β-sitosterol intervention was evaluated using fundus photography, histopathology(HE staining), and electroretinography(ERG). Network pharmacology was employed to screen potential targets of β-sitosterol in ARMD, and molecular docking was used to validate the binding ability between β-sitosterol and these targets. The impact of β-sitosterol on ARPE-19 cell viability and apoptosis pathways was analyzed using CCK-8 assay, Hoechst staining, and Western blotting.RESULTS: The β-sitosterol significantly alleviated structural damage in the retinas of model mice(increased retinal and outer nuclear layer thickness, reduced yellowish-white drusen-like deposits)and functional impairment(partial restoration of a-wave and b-wave amplitudes). Network pharmacology identified PON1 as a key target of β-sitosterol; molecular docking demonstrated that β-sitosterol binds to PON1 via hydrophobic interactions and hydrogen bonds. In vitro experiments showed that β-sitosterol(10 μmol/L)significantly increased ARPE-19 cell viability(P<0.01), reduced apoptosis(P<0.01), upregulated PON1 expression(P<0.01), and concurrently suppressed cleaved-Caspase3 expression(P<0.01).CONCLUSION: The β-sitosterol likely protects against oxidative stress-induced retinal damage by modulating PON1 to suppress the Caspase3-dependent apoptotic pathway. These findings provide experimental evidence supporting the development of β-sitosterol as a novel therapeutic agent for dry ARMD.

Objective:To establish ulcerative colitis(UC)rat model of spleen deficiency and dampness,and to explore effect of Jianpi-Huazhu pill and its different deconditions on TLR-4/MyD88/NF-κB pathway.Methods:A total of 64 Wistar rats were ran-domly divided into normal control group(n=8)and model group(n=56).UC rat model was established by traditional Chinese medi-cine syndrome combined with ethanol-2,4,6-trinitrobenzene sulfonic acid enema method.After successfully modeling,rats were ran-domly divided into model group(M),Mesalazine group(A),Jianpi-Huazhi pill group(B),Jianpi-Qinghua decoction group(C),Jianpi-Qinghua-Huoxue decoction group(D),Jianpi-Qinghua-Daozhi decoction group(E)and Qinghua-Daozhi-Huoxue decoction group(F),with 8 rats in each group,given corresponding drugs by gavage for 4 weeks.At end of course of treatment,all rats were sacrificed and samples were taken.Changes of body weight,disease activity and pathological changes of colon were observed.TNF-α expression in colon tissue was detected by ELISA and immunohistochemistry.RT-PCR and Western blot were used to detect mRNA and protein expressions of TLR-4,MyD88 and NF-κB in rat colon tissue.Results:Rats weight in Jianpi-Huazhi pill group,Jianpi-Qinghua decoction group,Jianpi-Qinghua-Huoxue decoction group and Jianpi-Qinghua-Daozhi decoction group were obviously higher than that of model group(P<0.01),all treatment groups could obviously improve UC model rat pathological damage and disease activity index in colon tissue,and Jianpi-Huazhi pill group and Jianpi-Qinghua-Huoxue group showed better efficacy.All treatment groups could inhibit mRNA and protein expressions of TLR-4,MyD88 and NF-κB in colon tissue(P<0.001).Mesalazine group,Jianpi-Huazhi pill group,Jianpi-Qinghua-Daozhi group and Qinghua-Daozhi-Huoxue group were significantly better than Jianpi-Qinghua group and Jianpi-Qinghua-Huoxue group in reducing NF-κB mRNA and protein expressions(P<0.05).All groups could reduce expres-sion of TNF-α in colon tissue(P<0.001),and there was no significant difference between groups(P>0.05).Conclusion:Jianpi-Huazhi pill and its various deconditions may play roles through TLR-4/MyD88/NF-κB pathway.Among them,Coptid-Rhizoma coptifo-lia,stews woody incense,Fengwei herb and gung ginger may be core drugs of this recipe,which has certain guiding significance for clinical practice.

Critical care medicine-related treatment is an interdisciplinary and multi-professional process,often leading to secondary or concomitant mental disorders in clinical practice.Currently,there is no consensus on the pharmacological treatment of related mental illnesses in China.The Chinese Society of Psychosomatic Medicine collaborated with the Critical Care Medicine expert group to form a consensus writing expert group.After a systematic review of relevant literature,summarizing published domestic and foreign literature,and extensive discussions,the consensus was developed.The consensus elaborates on the principles and processes of the standardized use of psychotropic drugs in critical care medicine,as well as the clinical indications,precautions,and specific drug selection of various psychiatric medications,providing feasible suggestions and guidance for the clinical application of psychiatric medications in the intensive care unit.

Objective To explore the dynamic changes in monoamine oxidase A(MAOA)and forkhead box A1(FOXA1)levels during neuroendocrine differentiation(NED)in prostate cancer,providing new strategies for the treatment of neuroendocrine prostate cancer.Methods Cell models and mouse transplantation models of NED were established through long-term sustained induction with enzalutamide(ENZ).Dynamic expression of MAOA and FOXA1 in NED was detected by Western Blot and Real-time PCR.GEO database data were selected to analyze the dynamic trends in MAOA and FOXA1 levels in multiple NED models.We constructed a mouse transplantation model of human prostate cancer cell lines and analyzed the dynamic expression of MAOA and FOXA1 in the in vivo NED model by immunohistochemistry.MAOA expression was disrupted with lentiviral transfection,and the impact on FOXA1 was detected.Results Both MAOA and FOXA1 concentrations showed dynamic characteristics,increasing and then decreasing during the NED process.Knockdown of MAOA in prostate cancer cells led to decreased expression of FOXA1.This MAOA may play different roles at different stages of NED by acting through FOXA1.Conclusions Both MAOA and FOXA1 levels showed increasing,then decreasing,trends during NED.The expression of MAOA affected the level of FOXA1,and MAOA/FOXA1 may play a dynamic regulatory role in the NED process.

Objective To develop an expert consensus on subcutaneous injection nursing for allergic asthma in children,standardize nursing practice to reduce the occurrence of related adverse reactions.Methods The clinical guideline,expert consensus,systematic review,evidence summary and original research on subcutaneous injection of monoclonal antibody drug for children with allergic asthma were comprehensively searched in domestic and foreign databases.The time limit for retrieval was from the establishment of databases until August 2023.Combined with clinical practice experience,the first draft of the consensus was formed.From December 2023 to February 2024,27 experts were invited to conduct 2 rounds of expert letter consultation,revise and improve the contents of the first draft,and expert demonstration was conducted,and finally a consensus final draft was formed.Results The effective recovery rate of the 2 rounds of letter consultation questionnaires was 100％;the authority coefficient of experts was 0.88;the judging basis coefficient was 0.93;the familiarity coefficient was 0.83.In the 2 rounds of correspondence,the Kendall concordant coefficients of expert opinions were 0.241 and 0.252,respectively(P＜0.001 for both).The consensus includes 6 parts,including personnel management,environmental layout,indications and contraindications,subcutaneous injection operation norms,identification and treatment of adverse reactions,and health education.Conclusion The consensus is strongly scientific and practical,and can provide guidance for nursing practice of subcutaneous injection of monoclonal antibodies in children with allergic asthma.

Objective:To evaluate the diagnostic efficacy of the multiparametric MRI (mpMRI) deep learning artificial intelligence (AI) analysis system combined with 68Ga-prostate specific membrane antigen (PSMA) PET for prostate cancer. Methods:Data of 103 patients (age: 45-85 years) who underwent 68Ga-PSMA PET/MR at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from May 2018 to October 2023 for suspected or confirmed prostate cancer were retrospectively collected. ROI was delineated to measure SUV max of primary tumor or prostate, and a deep learning AI system was applied to analyze MR images of the prostate. The diagnostic efficacies of T 2 weighted imaging (WI), diffusion WI (DWI), mpMRI, PET SUV max, and PET/MR for prostate cancer were assessed, with using the pathological results as the gold standard. Results:Among 103 patients, 82 cases (79.61%) were with prostate cancer. PET unimodality demonstrated the best specificity (100%, 21/21), positive predictive value (100%, 58/58), and AUC (0.860, 95% CI: 0.777-0.920). The mpMRI AI analysis provided rapid diagnostic results and the sensitivity and accuracy were improved by combining with PET (sensitivities of PET, mpMRI and the combination of the two were 70.73%(58/82), 86.59%(71/82), and 92.68%(76/82), respectively; the accuracies were 76.70%(79/103), 81.55%(84/103) and 86.41%(89/103), respectively). Among 44 patients with negative PET, 30 patients received an accurate diagnosis when the results of mpMRI AI analysis were added. Conclusions:68Ga-PSMA PET demonstrates good specificity for prostate cancer and mpMRI AI analysis is time-saving. The combined application improves the diagnostic sensitivity and accuracy, which provides a valuable tool for 68Ga-PSMA PET/MR image analysis.

Objective:To evaluate the efficacy and safety of 308-nm excimer lamp and 308-nm excimer laser in the treatment of pediatric vitiligo.Methods:Clinical data were collected from children with stable vitiligo who received targeted phototherapy at the Department of Dermatology of Xijing Hospital from 2010 to 2015, and retrospectively analyzed. The patients were treated with either 308-nm excimer laser or 308-nm excimer lamp, and all were given topical drugs. The treatment lasted for at least 3 months, and follow-up for at least 6 months. The severity of vitiligo was assessed using the Vitiligo Area and Severity Index (VASI) score. The efficacy was evaluated after 3 months of treatment, and at least a 50% reduction in the VASI score (VASI50) was defined as "effectiveness". A logistic regression model was constructed using treatment efficacy as the dependent variable to screen factors related to the treatment outcome. The Wilcoxon signed-rank test was used to compare skewed data before and after treatment. Adverse reactions during treatment were recorded to evaluate the safety of targeted phototherapy.Results:A total of 194 children with stable vitiligo were included, comprising 103 males (53.1%) and 91 females (46.9%), with the age being 6 to 14 (10.2 ± 2.3) years. Among them, 138 (71.1%) received 308-nm excimer laser therapy, while 56 (28.9%) received 308-nm excimer lamp therapy. The VASI score ( M [ Q1, Q3]) was 0.12 (0.05, 0.40) at the baseline, significantly decreased to 0.06 (0.02, 0.19) after 3 months of treatment ( Z = 12.02, P < 0.001). After 3 months of treatment, 52 patients achieved VASI50, and 30 achieved VASI75, resulting in an overall response rate of 42.3% (82/194). Specifically, in the 308-nm excimer laser group, 38 patients achieved VASI50 and 26 achieved VASI75, with a response rate of 46.4% (64/138) ; in the 308-nm excimer lamp group, 14 patients achieved VASI50 and 4 achieved VASI75, yielding a response rate of 32.1% (18/56). Univariate logistic regression analysis indicated that lesions located on the head and neck or the trunk were more prone to repigmentation compared with those on the limbs ( OR = 3.56, 95% CI: 1.15 - 11.02, P = 0.027; OR = 6.58, 95% CI: 1.81 - 23.96, P = 0.004, respectively) ; additionally, facial lesions around the eyes were more prone to repigmentation compared with lesions on other facial areas ( OR = 4.58, 95% CI: 1.10 - 19.11, P = 0.037), and hair involvement in vitiligo lesions on the head and neck made repigmentation less likely to occur compared with lesions without hair involvement ( OR = 0.31, 95% CI: 0.13 - 0.75, P = 0.010). Multivariate logistic regression analysis revealed that the periorbital region was the most favorable site for repigmentation among facial areas ( OR = 5.37, 95% CI: 1.18 - 24.34, P = 0.029), and hair involvement in vitiligo lesions on the head and neck was an independent risk factor for phototherapy-induced repigmentation ( OR = 0.28, 95% CI: 0.08 - 0.96, P = 0.042). Among the 194 patients treated with targeted phototherapy for 3 months, 33 experienced short-term treatment-related adverse reactions, including erythema, blisters, desquamation, itching, and pain; most adverse reactions were mild, and no severe adverse reactions were observed. Conclusion:Targeted phototherapy using 308-nm excimer laser or 308-nm excimer lamp was safe and effective for the treatment of pediatric vitiligo.