Objective: To evaluate the intervention effect of school based salt reduction health education, so as to provide a scientific basis for constructing a more effective and sustainable salt reduction intervention model for children. Methods: According to a randomized controlled trial design, in June 2022, probability proportional to size sampling was used to select 501 second grade students (248 in the control group and 253 in the intervention group) from 10 primary schools in Zhenjiang (intervention group) and 10 primary schools in Yangzhou (control group), Jiangsu Province. An one year school based salt reduction health education intervention was implemented. This included 20 online and 8 offline health education sessions, monitoring of salt consumption in the canteen, and the establishment of a salt reduction environment on campus. The control group received no additional salt reduction interventions. A questionnaire survey and 24 hour urinary sodium test were conducted before and after the intervention. The difference in differences method was used to evaluate the intervention effect. Results: After the intervention, the intervention group showed significant net intervention effects in knowledge aspects, including knowing that primary school students consume less salt than adults ( OR=3.55,95%CI =1.69-7.47), daily salt intake of primary school students ( OR=6.64,95%CI =3.71-11.87), long term high salt intake leading to hypertension ( OR=6.83,95%CI =3.93-11.91), low salt intake not causing hair graying ( OR= 1.66 ,95%CI =1.00-2.75), salt content in food labels ( OR=4.56,95%CI =2.63-7.91), and common high salt foods ( OR=3.39,95%CI =1.87-6.14) (all P <0.05). In terms of attitude, the net intervention effect for having a positive attitude toward using less salt in home cooking was significantly increased ( OR=1.88,95%CI =1.13-3.12, P <0.05). There were no statistically significant net intervention effects for salt reduction related behaviors (all P >0.05). There was no statistically significant difference in the changes of 24 hour urinary sodium between the intervention group and the control group before and after intervention ( P >0.05). Conclusions School based salt reduction health education effectively improves students salt reduction knowledge and attitudes but has a limited effect on behavior change. The home-school collaboration should be strengthened, and the dietary environment should be optimized simultaneously.

Objective To investigate the expression characteristics of the transcription factor E2F2 in clear cell renal cell carcinoma (ccRCC), its impact on patient prognosis, and its potential role in the tumor immune microenvironment, with validation using clinical samples and functional assays. Methods RNA sequencing data and clinical information of ccRCC patients were obtained from the TCGA database; GSE53757 and GSE66272 datasets were downloaded from the GEO database as external validation cohorts. The expression difference of E2F2 between ccRCC tissue and normal tissue was compared, and the relationship between E2F2 expression and clinical pathological characteristics was analyzed. Kaplan-Meier (KM) survival analysis with log-rank test was performed to evaluate the effects of E2F2 on overall survival (OS), progression-free survival (PFS), and disease-specific survival (DSS). The prognostic efficacy of E2F2 in predicting 1-, 3- and 5-year survival was evaluated using receiver operating characteristic (ROC) curve. GSEA was performed to identify E2F2-related signaling pathways, and the ESTIMATE and CIBERSORT algorithms were used to assess the relationship between E2F2 expression level and tumor immune cell infiltration and immune microenvironment. Twenty pairs of surgically resected and pathologically confirmed ccRCC tissues and matched adjacent non-tumor tissues were collected from our hospital, and immunohistochemistry (IHC) was performed to detect the protein expression of E2F2. Human ccRCC cell line 786-O was used for functional assays;shRNA was used to knock down E2F2 expression (constructing stable shE2F2#1 and shE2F2#2 cell lines), and qRT-PCR and Western blot were performed to verify knockdown efficiency, followed by MTT, colony formation, and Transwell migration assays to evaluate the effects of E2F2 on the biological behaviors of ccRCC cells. Results E2F2 was significantly upregulated in ccRCC tissues (the same results in the verification set). Higher E2F2 expression was associated with advanced histological grade, clinical stage and higher TNM classification (P＜0.05). KM analysis showed that patients in the E2F2 high-expression group had worse OS, PFS, and DSS (P=0.019, 0.036, ＜0.001); the ROC curves showed area under the curve (AUC) of E2F2 of predicting 1-, 3- and 5- year survival of ccRCC patients were 0.844, 0.851 and 0.815, respectively. GSEA revealed that the E2F2 low-expression group was enriched in multiple metabolism-related pathways, whereas the E2F2 high-expression group was associated with immune-related pathways. Immune analysis demonstrated that high E2F2 expression was associated with increased immune scores, increased proportion of immune cells, higher tumor mutation burden, and potentially stronger immunotherapy response. IHC results showed that the E2F2 immunoreactivity score in ccRCC tissues was significantly higher than that in adjacent non-tumor tissues (P＜0.05). Functional assays indicated that E2F2 knockdown significantly inhibited the proliferation, colony formation, and migration of ccRCC cells. Conclusion E2F2 is highly expressed in ccRCC and may be involved in tumorigenesis and progression through modulation of the immune microenvironment. Its expression level is closely associated with patient prognosis, and E2F2 has the potential to serve as a prognostic biomarker and immunotherapeutic target in ccRCC.

ObjectiveTo explore the sequential effects of hypoxic exercising on miR-27/PPARγ and lipid metabolism target gene and protein expression levels in the obesity rats’ liver. Methods13-week-old male diet-induced obesity rats were randomly divided into three groups (n＝10): normal oxygen concentration quiet group (N), hypoxia quiet group (H), hypoxic exercise group (HE). Exercise training on the horizontal animal treadmill for 1 h/d, 5 d/week for a total of 4 week, and the intensity of horizontal treadmill training was 20 m/min (hypoxic concentration was 13.6%). Comparison of the weights of perirenal fat and epididymal fat in rats across different groups and calculation of Lee’s index based on body weight and body length of rats in each group were done. And the serum concentrations of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) levels were detected. RT-PCR and Western Blot were used to detect the levels of miR-27, PPARγ, CYP7A1 and CD36. ResultsHypoxic exercise decreased the expression levels of miR-27 in the obese rats’ liver, however, the expression level of PPARγ was gradually increased. The expression levels of miR-27 in HE group were significantly lower than N group (P<0.05). The expression levels of PPARγ mRNA in N group were significantly lower than H group (P<0.05), especially lower than HE group (P<0.01). The protein expression of PPARγ protein in N group was significantly lower than that other groups (P<0.01). The expression of lipid metabolism-related genes and proteins increased in the obese rats’ liver. The expression of CYP7A1 mRNA in N group was significantly lower than H group (P<0.05), especially lower than HE group (P<0.01). The expression of CYP7A1 protein in the obese rats’ liver in N group was extremely lower than H group and HE group (P<0.01). The protein expression of CD36 in N group was significantly lower than that in HE group (P<0.05). Hypoxia exercise improved the related physiological and biochemical indexes of lipid metabolism disorder. The perirenal fat weight of obese rats in HE group was extremely lower than N group and H group (P<0.01), and the perirenal fat weight in N group was significantly higher than H group (P<0.05). The epididymal fat weight in N group was significantly higher than H group (P<0.05), and extremely higher than HE group (P<0.01). The Lee’s index in HE group was extremely lower than N group and H group (P<0.01). The serum concentration of TC in obese rats in HE group was extremely lower than N group and H group (P<0.01). The serum concentration of TG in HE group was extremely lower than N group and H group (P<0.01). The serum concentration of LDL-C in N group was extremely higher than HE group (P<0.01). The serum concentration of HDL-C in N group was extremely lower than H group (P<0.01). ConclusionHypoxia and hypoxia exercise may negatively regulate the levels of PPARγ by inhibiting miR-27 in the obese rats’ liver, thereby affecting the expression of downstream target genes CYP7A1 and CD36, and promoting cholesterol, fatty acid oxidation and HDL-C transport in the liver, and ultimately the lipid levels in obese rats were improved. The effect of hypoxia exercise on improving blood lipid is better than simple hypoxia intervention.

ObjectiveTo investigate the anti-inflammatory, antioxidant, and goblet cell-stimulating effects of a suspension of Ophiopogon japonicus (L. f.) Ker Gawl. (O. japonicus, Mai Dong) extract combined with hyaluronic acid (HA) in the mouse model with dry eye disease (DED).MethodsA DED mouse model was induced using benzalkonium chloride (BAK), followed by treatment with O. japonicus extract-containing eye drops at varying concentrations. Experimental groups included a normal control, a DED model control, a positive control, and an O. japonicus extract-treated group. Corneal fluorescein staining and tear break-up time (TBUT) were used to assess tear film stability and ocular surface integrity. Enzyme-linked immunosorbent assay (ELISA) measured inflammatory factor levels in corneal and conjunctival tissues, whereas Western blot (WB) analyzed key antioxidant and inflammatory markers, including nuclear factor erythroid 2-related factor (2Nrf2) and heme oxygenase 1 (HO-1). Periodic acid-schiff (PAS) staining and immunofluorescence were used to evaluate goblet cell density and mucin secretion.ResultsO. japonicus extract significantly improved corneal damage, reduced fluorescein staining scores, prolonged TBUT, and increased tear secretion. It downregulated inflammatory markers, including interleukin-8 (IL-8), interleukin-1β (IL-1β), and interferon-γ (IFN-γ) while upregulating Nrf2, HO-1, and the interleukin-13 (IL-13)/IFN-γ ratio, alleviating oxidative stress and inflammation. PAS staining showed increased conjunctival goblet cell density and restored mucin secretion, enhancing tear film stability.ConclusionO. japonicus extract demonstrated significant anti-inflammatory, antioxidant, and goblet cell-stimulating effects in a DED model, with good biocompatibility and promising therapeutic potential. Future research should optimize extraction processes and validate their efficacy and safety in clinical settings.

Objective:To evaluate the radiological and functional outcomes of moderate to severe hallux valgus patients with enlarged distal metatarsal articular angle (DMAA) underwent modified Chevron osteotomy.Methods:The clinical data of patients with moderate and severe hallux valgus with increased distal metatarsal joint angle who accepted surgery operation in the Department of Foot and Ankle Surgery of Yantaishan Hospital from October 2020 to December 2022 were retrospectively analyzed. All patients underwent modified Chevron osteotomy. Taking the proximal end of the metatarsal head centre as the osteotomy apex, the vertical arm osteotomy line in the sagittal plane made an angle of ≤80° with the metatarsal stem, the horizontal plane was inclined to the lateral distal end of the metatarsal head by about 10°, and the sagittal plane metatarsal arm osteotomy line made an angle of ≥90° with the vertical arm osteotomy line; at the proximal osteotomy surface, another cuneiform bone with its base on the medial and its apex on the lateral was resected. The deformity correction was insufficient and Akin osteotomy was performed in combination. Weil osteotomy was performed in combination with metatarsalgia. Radiological assessment including the hallux valgus angle (HVA), intermetatarsal angle (IMA), DMAA, the joint congruity angle (JCA), forefoot bone width and soft tissue width was performed preoperatively and at last follow-up postoperatively. American Orthopedic Foot and Ankle Society/hallux metatarsophalangeal-interphalangeal scale (AOFAS/HMIS) was used for clinical and functional evaluation, total score from 0 to 100, with higher scores indicating better function.Visual analogue scale (VAS) was used for pain valuation, total score from 0 to 10, with higher scores indicating more pain. A questionnaire survey on patient satisfaction was conducted at the last follow-up. Shapiro-Wilk test was used for normal distribution test, and measurement data following normal distribution were represented as Mean±SD. Paired t-test was used for comparison before and after operation. Other indicators conformed to non-normal distribution were denoted by M( Q1, Q3) and were tested by Wilcoxon signed-rank test. P<0.05 was considered statistically significant. Results:Fifty-two feet of 48 patients (5 males, 43 females; mean age (52.4±14.9) years; range, 24 to 78 years) were enrolled. Before the operation, 8 feet combined with metatarsalgia, among them, 7 feet underwent modified Chevron+ Akin+ Weil osteotomy, and 1 foot underwent modified Chevron+ Weil osteotomy. Among the 44 feet without metatarsalgia, 11 feet underwent modified Chevron osteotomy and 33 feet underwent modified Chevron+ Akin osteotomy. The mean follow-up time was 17.8 months (12-24 months). The HVA angle decreased from 38.30°±7.59° before surgery to 10.00°±5.73° at the last follow-up; the IMA angle decreased from 16.08°(12.89°, 18.24°) to 4.81°(3.62°, 7.57°); the DMAA angle decreased from 18.35°(13.03°, 27.47°) to 4.52°(2.68°, 7.09°); JCA decreased significantly from 15.93°(10.25°, 23.06°) to 3.56°(1.71°, 6.98°); forefoot bone width decreased from (90.05±6.12) mm to (82.75±5.01) mm; forefoot soft tissue width decrease from 102.25(96.77, 107.15) mm to 98.08(91.01, 100.60) mm; the VAS decreased from 6(5.5, 7) points to 0(0, 0) points; the score according to the AOFAS/HMIS forefoot was increased from 49(42, 52.5) points to 90(83.5, 95) points; which were statistically significant compared with that before the operation (all P<0.01). There was no statistically significant difference in the first metatarsal length before the operation and at the last follow-up [54.60(52.86, 56.42) mm vs. 54.29(51.85, 56.35) mm, P>0.05]. In the post-operative period, there were 8 feet had limited metatarsophalangeal joint movement, 3 feet had limited interphalangeal joint movement, 5 feet had limited movement in both joints, which did not affect walking and function; 3 feet of partial recurrence of hallux valgus, 2 feet of screw irritation pain, 1 foot of cystic degeneration of the first metatarsal head, and no complications such as metastatic metatarsalgia. The satisfaction survey showed that the satisfaction rate of patients with the orthopedic effect was 90.4% (47/52). Conclusion:The modified Chevron osteotomy is effective in the treatment of moderate to severe hallux valgus with enlarged DMAA. Careful intraoperative operation and standardized postoperative rehabilitation training can reduce complications.

Objective To understand the clinical applicability and implementation of expert consensus on the implementation and removal of protective restraints in psychiatry,and to provide references for promoting the standardized practice of psychiatric protective restraints and updating the consensus.Methods By the convenience sampling method,a questionnaire survey was conducted among nurses from 480 hospitals in 30 provinces from June 15 to July 15,2024.The survey was conducted using the instrument for evaluating clinical applicability of guide-lines(version 2.0)and a self-compiled questionnaire on the clinical implementation of the restraint consensus.Results A total of 7,844 valid questionnaires were collected,with a valid questionnaire recovery rate of 93.78％.The results of clinical applicability scoring showed that the consensus had the lowest availability score(64.72％)and the highest acceptability score(76.74％).The results showed that nurses' receiving training and the level of their hospitals were the main influencing factors for scores in various dimensions(P＜0.05).4,774 participants(87.42％)believed that the application of consensus could enhance the standardization of nurses' restraint operations.The safety rate of the restraint consensus was 79.51％,and the economic ratio was 76.87％.Among the evaluators,1,739(22.17％)believed that there were implementation obstacles in the consensus.Conclusion The clinical applicability of the consensus is relatively good,and the application of the consensus helps to improve the standardization of clinical operations.In the future,efforts should be made to strengthen the promotion and training of the consensus,develop hierarchical promotion strategies according to the characteristics of medical institutions,and improve the quality of evidence for the consensus,so as to further enhance the clinical application effect of the consensus.

A child aged 5 years with pulmonary arterial hypertension was admitted to the First Affiliated Hospital of Xiamen University in December 2017. A truncated mutation in the bone morphogenetic protein receptor 2 (BMPR2) gene [Chr2(GRCh37):g.203395656delA] was detected, which might be responsible for the disease and the diagnosis of hereditary pulmonary arterial hypertension (HPAH) was confirmed. Genetic testing revealed that the child′s father also carried the same mutation in BMPR2 gene, but no gene mutation was detected in child′s mother and young brother; however, no HPAH was developed in child′s father and other family members. The child was treated with targeted drugs for pulmonary arteries with poor response, and died in April 2019. Later, the child′s mother accidentally became pregnant. Gene sequencing test of the amniotic fluid showed that the fetus also carried the BMPR2 gene mutation; the pregnancy was terminated after genetic counseling. HPAH has the clinical characteristics of early onset, rapid progression, and poor prognosis, and the BMPR2 gene mutation is an important pathogenic factor. For HPAH patients with unknown etiology, particularly for pediatric patients, genetic testing is recommended to identify the cause and to make an appropriate clinical management plan.

The circadian clock plays a critical role in regulating various physiological processes, including gene expression, metabolic regulation, immune response, and the sleep-wake cycle in living organisms. Post-translational modifications (PTMs) are crucial regulatory mechanisms to maintain the precise oscillation of the circadian clock. By modulating the stability, activity, cell localization and protein-protein interactions of core clock proteins, PTMs enable these proteins to respond dynamically to environmental and intracellular changes, thereby sustaining the periodic oscillations of the circadian clock. Different types of PTMs exert their effects through distincting molecular mechanisms, collectively ensuring the proper function of the circadian system. This review systematically summarized several major types of PTMs, including phosphorylation, acetylation, ubiquitination, SUMOylation and oxidative modification, and overviewed their roles in regulating the core clock proteins and the associated pathways, with the goals of providing a theoretical foundation for the deeper understanding of clock mechanisms and the treatment of diseases associated with circadian disruption.
Protein Processing, Post-Translational/physiology* ; Circadian Rhythm/physiology* ; Humans ; Animals ; CLOCK Proteins/physiology* ; Circadian Clocks/physiology* ; Phosphorylation ; Acetylation ; Ubiquitination ; Sumoylation

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

OBJECTIVES: To analyze the differentially expressed exosomal miRNAs in patients with chronic heart failure (CHF) complicated by hyperuricemia (HUA) and explore their potential as novel diagnostic molecular markers and their target genes. METHODS: This study was conducted among 30 CHF patients with HUA (observation group) and 30 healthy volunteers (control group) enrolled between September, 2020 and September, 2023. Peripheral blood samples were collected from 6 CHF patients with HUA for analyzing exosomal miRNAs by high-throughput sequencing, and the results were validated in the remaining 24 patients using qRT-PCR. GO and KEGG enrichment analyses were performed to predict the the target genes of the identified differential miRNAs. We also validated the differentially expressed miRNAs by animal experiment. RESULTS: A total of 42 differentially expressed exosomal miRNAs were detected in observation group by high-throughput sequencing; among them, miR-27a-5p was significantly upregulated (P=0.000179), and miR-139-3p was significantly downregulated (P=0.000058). In the 24 patients with both CHF and PUA, qRT-PCR validated significant upregulation of miR-27a-5p (P=0.004) and downregulation of miR-139-3p (P=0.005) in serum exosomes. When combined, miR-27a-5p and miR-139-3p had a maximum area under the curve (AUC) of 0.899 (95% CI: 0812-0.987) for predicting CHF complicated by HUA. GO and KEGG enrichment analyses suggested that the differential expressions of miR-27a-5p and miR-139-3p was associated with the activation of the AMPK-mTOR signaling pathway to activate the autophagic response. We obtained the same conclusion from animal experiment. CONCLUSIONS Upregulated exosomal miR-27a-5p combined with downregulated exosomal miR-139-3p expression can serve as a novel molecular marker for diagnosis of CHF complicated by HUA, and their differential expression may promote autophagy in cardiomyocytes by activating the AMPK-mTOR signaling pathway.
Humans ; Hyperuricemia/diagnosis* ; Heart Failure/genetics* ; MicroRNAs/metabolism* ; Exosomes/metabolism* ; Chronic Disease ; Male ; Female ; Middle Aged ; Animals