Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Rheumatoid Arthritis (RA) is a critical disease that endangers the health of the Chinese population. At present, there are still many deficiencies in the diagnosis and treatment of RA in China. The 2024 Chinese Guidelines for the Diagnosis and Treatment of Rheumatoid Arthritis addresses 10 important clinical issues in the diagnosis and treatment of RA, and provides evidence-based recommendations based on the latest domestic and international literature, with consideration of the actual situation of RA diagnosis and treatment in China. The guidelines comprehensively cover the diagnosis of RA, imaging examinations, treatment goals, follow- up monitoring, initial treatment plans, treatment adjustments, the application of glucocorticoids, drug tapering, and health education. They will promote the RA diagnosis and treatment levels and improve the prognosis of RA patients in China.

OBJECTIVE To investigate the changes in serum metabolites of mice with radiation-induced intestinal injury under the intervention of baicalein and the changing characteristics of endogenous biological small molecules during the process of baicalein's participation in the prevention and treatment of radiation-induced intestinal injury through the metabolomics method based on GC-MS technology,in order to explore the potential regulatory mechanism of baicalein.METHODS A mouse radioactive intestinal injury model was established and randomly divided into normal control group,model group,low-dose baicalein group and high-dose baica-lein group.Baicalein was administered by gavage.Gas chromatography-mass spectrometry(GC-MS)technology was used to analyze the serum samples of mice in each group,and differential metabolites were screened through partial least squares-discriminant analysis(PLS-DA).Potential metabolic pathways were analyzed with MetaboAnalyst.RESULTS The pathological sections of mouse intesti-nal tissue showed that the high-dose and low-dose baicalein groups had a certain protective effect on radiation-induced intestinal dam-age.Metabolomic analysis showed that there were significant differences in the metabolic profiles of the blank control group,model group,low-dose and high-dose baicalein administration groups.After intragastric administration of baicalein,the endogenous metabo-lites in mice with radiation intestinal injury tended to normalize.The study screened out a total of 11 potential metabolic markers and 5 related metabolic pathways,among which pathways related to glucose metabolism,glutathione pathway,and ammonia metabolism were particularly significant.CONCLUSION Baicalein has a certain preventive and therapeutic effect on radiation-induced intestinal in-jury;baicalein participates in glucose metabolism and glutathione metabolism,and improving the endogenous substance disorder caused by radiation is its potential mechanism of action.

Objective To investigate the incidence of neonatal hyperphenylalaninemia (HPA) and analyze the characteristics of HPA gene mutations in the Yangzhou area. Methods From January 2013 to December 2022, 285, 549 newborns in Yangzhou were screened for HPA using either the ninhydrin fluorescence method or tandem mass spectrometry. Urinary pterin analysis, erythrocyte dihydrobiopterin reductase activity measurement and genetic diagnosis were performed to screen positive individuals. Results A total of 29 cases were confirmed as HPA, including 3 cases of tetrahydrobiopterin (BH₄) deficiency and 26 cases of phenylalanine hydroxylase (PAH) deficiency. The overall incidence of HPA in Yangzhou was 1/9, 847, with the incidence of PAH deficiency being 1/10, 983, which were slightly higher than the national average but lower than other regions in Jiangsu Province. Among the cases, 13 (44.83%) were classic phenylketonuria (PKU), 7(24.14%) were mild PKU, and 6(20.69%) were mild HPA. Sixteen patients with PAH gene mutations were all compound heterozygotes, with one case exhibiting three-site mutations. PAH gene mutations were predominantly missense mutations, primarily concentrated in exon 7, followed by exon 6, with E7 c.728G>A (21.21%) being the most frequent mutation. Three cases of BH₄ deficiency were detected with PTS gene mutations, including 1 homozygous mutation and 2 compound heterozygous mutations. E5 c.259C>T was the high-frequency PTS mutation gene in Yangzhou. Conclusion HPA has a certain incidence in Yangzhou, with classic PKU being the predominant type. This study clarified the characteristics of PAH and PTS gene mutations in Yangzhou, enriching the HPA gene database.

Objective:To investigate the effects of breast milk to total milk intake ratio during hospitalization on the duration of antibiotic therapy in preterm infants less than 34 weeks of gestation.Methods:Clinical data of preterm infants ( n=1 792) less than 34 gestational weeks were retrospectively collected in 16 hospitals of Jiangsu Province Neonatal-Perinatal Cooperation Network from January 1, 2019, to December 31, 2021. The days of therapy (DOT) were used to evaluate the duration of antibiotic administration. The median DOT was 15.0 d (7.0-27.0 d). The patients were divided into four groups based on the quartiles of DOT: Q 1 (DOT≤7.0 d), Q 2 (7.0 d27.0 d) groups. According to the breast milk intake ratio (breast milk intake to total milk intake during hospitalization×100%), they were also divided into four groups: very-low-ratio breastfeeding group (breast milk intake ratio≤25%), low-ratio breastfeeding group (25%75%). Univariate analysis ( Chi-square test and Kruskal-Wallis rank-sum test) was used to analyze the factors influencing DOT. Spearman correlation analysis and trend Chi-square test were used to explore the relationship between breast milk intake ratio and DOT. After using multiple imputations to address missing data, two models were constructed after adjusting for different factors, and multinomial logistic regression model was applied to evaluate the effects of the breast milk intake ratio on DOT. Finally, sensitivity analysis was conducted to assess the stability of the models. Results:(1) Of the 1 792 preterm infants, there were 507 (28.3%) in the Q 1 group, 422 (23.5%) in the Q 2 group, 438 (24.4%) in the Q 3 group and 425 (23.7%) in the Q 4 group. (2) The median values of DOT in the very-low-ratio, low-ratio, medium-ratio and high-ratio breastfeeding groups were 20.0 d (11.0-31.0 d), 20.0 d (11.0-32.0 d), 13.0 d (6.0-25.8 d) and 10.0 d (4.0-21.0 d), respectively. Compared with the very-low-ratio and low-ratio breastfeeding groups, the medium-ratio and high-ratio breastfeeding groups had shorter DOT (all P<0.05). (3) After adjusting for factors with P<0.1 (prenatal glucocorticoid exposure, antimicrobial use within 24 h before delivery, gestational age at delivery, birth weight, Apgar score≤7 at 1 min, neonatal respiratory distress syndrome, infectious pneumonia and early-onset neonatal sepsis) between the DOT quartile groups, it showed that medium-ratio and high-ratio breastfeeding were protective factors in contrast to very-low-ratio breastfeeding in the Q 2, Q 3 and Q 4 groups as compared with the Q 1 group [Q 2 group: OR=0.50 (95% CI: 0.30-0.85) and OR=0.36 (95% CI: 0.26-0.51); Q 3 group: OR=0.31 (95% CI: 0.18-0.55) and OR=0.20 (95% CI: 0.14-0.29); Q 4 group: OR=0.22 (95% CI: 0.12-0.42) and OR=0.17 (95% CI: 0.12-0.26)]. Conclusion:Breast milk intake accounting for over 50% of total milk intake has a positive impact on reducing DOT in premature infants requiring antibiotics, which suggests that breastfeeding should be actively encouraged.

CD4+T cells have strong plasticity and can be polarized intovarious effector cells such as Th1,Th2,Th17 and Treg cells.Then they participate in the regulation of various inflammatory diseases.Its polarization can not only promote development of disease,but also inhibit progression of disease.Direction of polarization may also be different in different diseases or in different stages of the same disease.Therefore,this review aims to summarize and explore the regulatory role of CD4+T cell polarization in different inflam-matory diseases and its significance for disease prevention and treatment.

Tooth transposition is a challenge for orthodontists, especially in correcting the order of teeth. At present, the literature on transposition canines mainly focuses on epidemiological studies and case reports, and no systematic treatment guidance has been formed. In this article, the definition and classification, epidemiology and etiology, imaging diagnosis, treatment and risk control of transposed canines are systematically described in order to provide reference for clinical practice.

Long-term inflammation will develop into chronic inflammation and become inflammatory diseases.Antibiotics are commonly used in clinical practice to treat inflammatory diseases.But patients are prone to drug resistance.So we need to find new treatment.Chlorogenic acid is an organic compound extracted from honeysuckle and other plants.Its anti-inflammatory activity is strong,and it has a significant anti-inflammatory effect on inflammatory diseases in various systems.It has been shown that chlorogenic acid can regulate inflammation-related signaling pathways,such as nuclear factor κB(NF-κB)canonical signaling pathway,NF-κB atypical signaling pathway,nuclear factor-erythroid 2-related factor 2(Nrf2)canonical signaling pathway,and Nrf2 atypical signaling pathway,etc.It can up-regulate the expression of anti-inflammatory cytokines such as interleukin(IL)-4,IL-10,IL-13 and down-regulate the expression of pro-inflammatory cytokine such as IL-1β,IL-6,and IL-8.Although chlorogenic acid has a strong anti-inflammatory effect,but clinical trials and application still face many difficulties.In the future,the anti-inflammatory molecular mechanism of chlorogenic acid should be further studied to explore its clinical application value and improve new ideas for the treatment of inflammatory diseases.

Objective:To evaluate the effectiveness and prognosis of emergent transcatheter aortic valve replacement (TAVR) and to provide standardized procedural suggestion for the development of emergent TAVR in China.Methods:From January 2020 to April 2021, 12 patients who underwent emergent or salvage TAVR in the Second Affiliated Hospital Zhejiang University School of Medicine were retrospectively enrolled from the TORCH registry (Transcatheter Aortic Valve Replacement Single Center Registry in Chinese Population, a prospective cohort study; NCT02803294). Baseline, periprocedural and 30-day follow up data were collected. Post-operative data were compared with pre-operative data using Paired-Samples test.Results:Patients’ median Society of Thoracic Surgeons score (STS score) was 15.432%. There was a significant decrease of mean gradient after emergent TAVR procedure (1.69 m/s vs. 4.90 m/s, P<0.01). During the 30-day follow up, there were 1 patient (8.3%) died and 2 patients received permanent pacemaker implantation. No disabling stroke, acute kidney injury, major vascular complication occurred during the first month after emergent TAVR. Among the survival patients, there was a significant releasing of heart failure symptoms to New York Heart Association function stage Ⅰ/Ⅱ in 81.8% patients at 30-day follow up. Left ventricular ejection fraction also improved significantly from (47.4±9.5)% to 58.8±8.0% ( P= 0.026). The mean gradient were (1.57±0.30) cm 2 and no patients had a moderate or severe paravalvular leakage. Besides, a significant decrease of pro-B-type natriuretic peptide (1 089.9 pg/mL vs. 12 215.5 pg/mL , P=0.001) and troponin T (0.020 ng/mL vs. 0.337 ng/mL, P=0.003) were found at 30 days after emergent TAVR. Conclusions:For patients with severe aortic stenosis and acute cardiac decompensated, emergent TAVR is a safe and effective rescue treatment.

This review aims to interpret the interventions to improve physical function for children and young people with cerebral palsy, thus providing relevant suggestions.Relevant literatures published before November 2018 were systematically searched in Cochrane library, CINAHL, and Embase MEDLINE using the Grading of Recommendations Assessment, Development and Evaluation method.Consult with international experts and patients to assess evidence and recommend it.Based on 3 systematic reviews, 30 randomized clinical trials, and 5 pre-and post-treatment studies, a total of 13 recommendations were given.The guidelines recommend that, in order to achieve functional stan-dards, intervention measures should include, patient-selected goals, full-task practice in real-life settings, support for family empowerment, and a team approach.The age, ability, and child/family preferences were all needed to be considered.In order to improve walking ability, ground walking and treadmill training can be carried out.Various methods can promote the realization of hand use goals hand use, including the two-hand exercise training, constraint-induced moverment therapy, goal-oriented training and cognitive therapy.In terms of patient self-care, the guideline proposed that, the combination of full-task practice and auxiliary equipment can improve the independence of self-care and reduce the burden of care givers.Leisure goals could be achieved by the combination of the practice of the entire task with strategies to address environmental, personal, and social barriers.The intervention of children and adolescents with cerebral palsy should take into consideration of patient selection and the goal of full-task practice.The child/family preference, age and ability should be considered when clinical workers selecting specific interventions.