Objective:To explore the effect of intervention model based on comprehensive nutrition management on glucose and lipid metabolism and pregnancy outcome in patients with gestational diabetes mellitus (GDM).Methods:104 GDM patients admitted to Shanxi Bethune Hospital from February 2022 to March 2023 were randomly divided into control group and experimental group, with 52 cases in each group. The control group implemented routine management measures and nutrition guidance, while the experimental group implemented an intervention model based on comprehensive nutrition management on the basis of routine management. The indexes of glucose and lipid metabolism (glycosylated hemoglobin, fasting blood glucose, 2 h postprandial blood glucose, total cholesterol, triglyceride and low density lipoprotein cholesterol), pregnancy outcome, self-management ability and self-efficacy were compared between the two groups before and after intervention.Results:Before the intervention, there was no significant difference in general situation, glucose and lipid metabolism index, self-management ability and self-efficacy between the two groups ( P>0.05). After the intervention, the level of glucose and lipid metabolism index in the experimental group was significantly lower than that in the control group, with statistical significance ( P<0.05). The incidence of adverse pregnancy outcome in the experimental group was significantly lower than that in the control group, with statistical significance ( P<0.05). The scores of self-management ability and self-efficacy in the experimental group were significantly higher than those in the control group, with statistical significance ( P<0.05). Conclusion:The intervention model based on comprehensive nutrition management can effectively improve the glucose and lipid metabolism index and pregnancy outcome of GDM patients, and significantly improve their self-management ability and self-efficacy related to nutrition management, which has high clinical application and promotion value.

Objective To explore the interventional effect of repetitive transcranial magnetic stimulation (rTMS) on tardive dyskinesia (TD) in schizophrenic patients. Methods A total of 105 schizophrenic patients were selected as subjects and randomly divided into 1 Hz treatment group, 10 Hz treatment group and control group, with 35 patients in each group. All three groups received rTMS treatment for 12 weeks. The Abnormal Involuntary Movement Scale (AIMS), Scale for the Assessment of Negative Symptoms (SANS), Positive and Negative Syndrome Scale (PANSS) and Treatment Emergent Symptom Scale (TESS) scores were compared among the three groups. Physiological indicators such as electrocardiogram, blood routine, blood biochemistry and hormone levels were monitored. Results After treatment, the total AIMS scores in the 1 Hz and 10 Hz treatment groups were significantly lower than before treatment, and those in the 1 Hz and 10 Hz treatment groups were significantly lower than those in the control group (P < 0.05). The reduction rates of AIMS scores in the 1 Hz and 10 Hz treatment groups were 68.6% and 65.7%, respectively, which were significantly higher than the 22.9% in the control group (P < 0.05). After treatment, the total SANS and PANSS scores in the 1 Hz and 10 Hz treatment groups were significantly lower than before treatment, and those in the 1 Hz and 10 Hz treatment groups were significantly lower than those in the control group (P < 0.05). There was no statistically significant difference in the total AIMS score, efficacy and total PANSS score between the 1 Hz and 10 Hz treatment groups (P>0.05). There were no significant differences in the total TESS scores and physiological indicators among the three groups before and after treatment (P>0.05). Conclusion Both 1 Hz and 10 Hz rTMS can effectively improve TD in schizophrenic patients with good safety and have no significant side effects or physiological damage.

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.

Objective:To summarize the clinical manifestations, experiences in diagnosis and treatment of arrhythmogenic cardiomyopathy (ACM) in children.Methods:A retrospective analysis of the clinical manifestations, laboratory tests, radiological features, treatment and follow-up results was conducted in 11 children diagnosed with ACM at the center of congenital heart disease, Beijing anzhen hospital from May 2010 to March 2022.Results:A total of 11 patients aged 2 to 16 years, including 5 males and 6 females were diagnosed with ACM. The clinical manifestations included decreased activity tolerance (7 patients), heart failure (4 patients), syncope or sudden death (3 patients), palpitation (3 patients), and chest tightness and pain (3 patients). Electrocardiogram showed right bundle branch block in 9 cases, paroxysmal ventricular tachycardia in 4 cases, frequent premature ventricular contraction in 4 cases, ventricular pre-excitation in 1 case, left bundle branch block in 1 case, and first degree atrioventricular block in 2 cases. Echocardiography showed enlargement of the right heart, widening of the right ventricular outflow tract, and thinning and bulging of the local wall of the right ventricle with reduced pulsation. Ventricular thrombosis was found in 2 cases. Six children underwent cardiac magnetic resonance imaging, which mainly showed severe enlargement of the right heart, thin free wall of the right ventricle, decreased right heart function, enhanced right ventricular myocardium, and formation of right ventricular aneurysm. Two children underwent myocardial biopsy examination and presented with typical pathological changes of ACM. Genetic tests in five patients revealed DSG2 gene mutation in 2 cases, PKP2 gene mutation in 2 cases, and MYH6 gene mutation in 1 case. All patients received anti heart failure treatment and antiarrhythmic drugs. Two children received anticoagulant treatment due to ventricular thrombosis. Radiofrequency ablation was performed in 2 patients. Glenn procedure was performed in 4 patients, and heart transplantation was performed in 1 patient due to progressive heart failure. The follow-up period ranged from 6 months to 12 years. Two cases died of right heart failure, 6 cases had different degrees of heart failure, 1 case had intermittent chest tightness and pain, and 2 cases were stable.Conclusions:ACM is a progressive genetic cardiomyopathy characterized by decreased activity tolerance, cardiac failure and arrhythmia in pediatric patients. The diagnosis is mainly based on clinical manifestations, electrocardiogram, cardiac imaging changes, and genetic testing. Early detection, diagnosis, and personalized treatment can improve the prognosis.

Background/Aims: Gastric intestinal metaplasia (GIM), a common precancerous lesion of gastric cancer, can be caused by bile acid reflux. GATA binding protein 4 (GATA4) is an intestinal transcription factor involved in the progression of gastric cancer. However, the expression and regulation of GATA4 in GIM has not been clarified. Methods: The expression of GATA4 in bile acid-induced cell models and human specimens was examined. The transcriptional regulation of GATA4 was investigated by chromatin immunoprecipitation and luciferase reporter gene analysis. An animal model of duodenogastric reflux was used to confirm the regulation of GATA4 and its target genes by bile acids. Results: GATA4 expression was elevated in bile acid-induced GIM and human specimens.GATA4 bound to the promoter of mucin 2 (MUC2) and stimulate its transcription. GATA4 and MUC2 expression was positively correlated in GIM tissues. Nuclear transcription factor-κB activation was required for the upregulation of GATA4 and MUC2 in bile acid-induced GIM cell models. GATA4 and caudal-related homeobox 2 (CDX2) reciprocally transactivated each other to drive the transcription of MUC2. In chenodeoxycholic acid-treated mice, MUC2, CDX2, GATA4, p50, and p65 expression levels were increased in the gastric mucosa. Conclusions GATA4 is upregulated and can form a positive feedback loop with CDX2 to transactivate MUC2 in GIM. NF-κB signaling is involved in the upregulation of GATA4 by chenodeoxycholic acid.

Background/Aims: Cancer stem cells (CSCs) are believed to drive tumor development and metastasis. Activin and hepatocyte growth factor (HGF) are important cytokines with the ability to induce cancer stemness. However, the effect of activin and HGF combination treatment on CSCs is still unclear. Methods: In this study, we sequentially treated colorectal cancer cells with activin and HGF and examined CSC marker expression, self-renewal, tumorigenesis, and metastasis. The roles of forkhead box M1 (FOXM1) and sex-determining region Y-box 2 (SOX2), two stemness-related transcription factors, in activin/HGF-induced aggressive phenotype were explored. Results: Activin and HGF treatment increased the expression of CSC markers and enhanced sphere formation in colorectal cancer cells. The tumorigenic and metastatic capacities of colorectal cancer cells were enhanced upon activin and HGF treatment. Activin and HGF treatment preferentially promoted stemness and metastasis of CD133 + subpopulations sorted from colorectal cancer cells. FOXM1 was upregulated by activin and HGF treatment, and the knockdown of FOXM1 blocked activin/HGF-induced stemness, tumorigenesis, and metastasis of colorectal cancer cells.Similarly, SOX2 was silencing impaired sphere formation of activin/HGF-treated colorectal cancers. Overexpression of SOX2 rescued the stem cell-like phenotype in FOXM1-depleted colorectal cancer cells with activin and HGF treatment. Additionally, the inhibition of FOXM1 via thiostrepton suppressed activin/HGF-induced stemness, tumorigenesis and metastasis. Conclusions Sequential treatment with activin and HGF promotes colorectal cancer stemness and metastasis through activation of the FOXM1/SOX2 signaling. FOXM1 could be a potential target for the treatment of colorectal cancer metastasis.

【Objective】 To investigate the predictive value of preoperative platelet/lymphocyte ratio (PLR) and neutrophil/lymphocyte ratio (NLR) (NLR-PLR) in peripheral blood for the prognosis of patients with upper urinary tract urothelial carcinoma (UTUC) undergoing radical surgery. 【Methods】 The clinical data of 104 UTUC patients who underwent radical nephroureterectomy plus bladder sleeve resection in our hospital during Jan.2015 and Dec.2020 were retrospectively analyzed. The receiver operating characteristic (ROC) curve was drawn according to NLR and PLR, the optimal cut-off values of NLR and PLR were calculated, and NLR-PLR was determined accordingly. The patients were divided into NLR-PLR group 1 (PLR ≥161.46 and NLR≥ 2.51) and NLR-PLR group 0 (remaining patients). Chi-square test was used for comparison between groups, and the Kaplan-Meier method was used to draw survival curves. According to the Cox univariate and multivariate risk regression models, the risk factors for decreased overall survival (OS) were determined. 【Results】 The optimal cut-off values of PLR and NLR were 161.46 and 2.51, respectively. There were 74 patients in the NLR-PLR group 0 and 30 in the NLR-PLR group 1. Cox multivariate regression analysis showed that T stage, maximum tumor diameter and NLR-PLR were independent risk factors for reduced OS (P<0.05). 【Conclusion】 Preoperative NLR-PLR is a potential predictor of the prognosis of UTUC patients. Higher NLR-PLR is associated with poorer prognosis.

Conjunctival melanoma (CM) is a rare and fatal malignant eye tumor. In this study, we deciphered a novel anti-CM mechanism of a natural tetracyclic compound named as cucurbitacin B (CuB). We found that CuB remarkably inhibited the proliferation of CM cells including CM-AS16, CRMM1, CRMM2 and CM2005.1, without toxicity to normal cells. CuB can also induce CM cells G2/M cell cycle arrest. RNA-seq screening identified KIF20A, a key downstream effector of FOXM1 pathway, was abolished by CuB treatment. Further target identification by activity-based protein profiling chemoproteomic approach revealed that GRP78 is a potential target of CuB. Several lines of evidence demonstrated that CuB interacted with GRP78 and bound with a K _d value of 0.11 μmol/L. Furthermore, ATPase activity evaluation showed that CuB suppressed GRP78 both in human recombinant GRP78 protein and cellular lysates. Knockdown of the GRP78 gene significantly induced the downregulation of FOXM1 and related pathway proteins including KIF20A, underlying an interesting therapeutic perspective. Finally, CuB significantly inhibited tumor progression in NCG mice without causing obvious side effects in vivo. Taken together, our current work proved that GRP78-FOXM1-KIF20A as a promising pathway for CM therapy, and the traditional medicine CuB as a candidate drug to hinder this pathway.

Background Organic ultraviolet (UV) filters are widely used in personal care products. So far, relevant studies on organic UV filters in indoor dust have been reported. Objective This study aims to establish a thermal desorption combined with gas chromatography-mass spectrometry (TD-GCMS) method to identify organic UV filters in indoor air collected from different indoor environments, so as to reveal the pollution levels and characteristics of organic UV filters in indoor environment. Methods Based on the standard indoor air sampling protocol, a total of 60 samples were collected from eight different kinds of indoor environments (male and female dormitory rooms, offices, labs, barber shops, printing shops, hotels, and private cars) on and nearby Minhang Campus of Shanghai Jiao Tong University from August to November, 2020. The concentrations of six common organic UV filters, including homosalate (HMS), 2-ethylhexyl salicylate (EHS), 3-(4-methylbenzylidene)-camphor (4-MBC), isoamyl 4-methoxycinnamate (IMC), octocrylene (OC), and octyl 4-methoxycinnamate (EHMC), in the air of different indoor environments were detected by TD-GCMS. Furthermore, the correlations of individual organic UV filters in different indoor environments were analysed. Results Under optimized detection conditions, the correlation coefficients of the quantitative standard curves of selected six organic UV filters were all at or above 0.997. The relative standard deviations of 1 mg·L⁻³ samples ranged from 1.74% to 7.11%, and the recoveries ranged from 67.17% to 106.5%. The relative standard deviations of 10 mg·L⁻³ samples ranged from 3.59% to 8.76%, and the recoveries ranged from 78.80% to 126.60%. The detection rates of the other five organic UV filters except IMC were all at or more than 92% in eight different kinds of indoor air. The median concentration of total organic UV filters was 75.17 ng·m⁻³, and EHS presented the highest median concentration of 28.55 ng·m⁻³. Regarding different indoor environments, the highest concentration of total organic UV filters was found in the female dormitory samples, 154.98 ng·m⁻³. The respective pair-analysis among HMS, EHMC, OC, and EHS of all indoor air samples reached a significant level of correlation (r=0.40-0.61, P<0.01). Conclusion The TD-GCMS method is satisfactory for the determination of organic UV filters in indoor air. EHS, EHMC, HMS, OC, and 4-MBC are identified in selected eight indoor environments, and they may have similar sources of pollution.

Objective To investigate the pollution levels of six indicator polychlorinated biphenyls (PCBs) in animal-derived foods in Hebei Province. Methods A total of 96 food samples (including beltfish, snakehead, egg, pork liver, pork and beef meat) were collected from Hebei Province in 2019. The contents of six indicator PCBs (PCB 28, PCB 52, PCB 101, PCB 138, PCB 153 and PCB180) in different food samples were determined using isotope dilution-high resolution gas chromatography-high resolution mass spectrometry (HRGC-HRMS). Results The contents of indicative PCBs in fish samples ranged from 0.12 to 0.32 ngg-1 fresh weight, while the content of PCBs in other samples ranged from 0.11 to 1.10 ng g-1 fat. PCB 138 and PCB 153 were the main compounds detected in fish samples, while PCB 28 and PCB 52 were the main compounds detected in other samples. The average estimated daily dietary intake of PCBs for residents in Hebei Province was 0.14 ng kg^-1·bw^-1·d^-1, and the highest contribution rate was beltfish (61.52%). Conclusion The pollution levels of indicator PCBs in animal-derived foods in Hebei Province are relatively low, and the residents has lower health risks through dietary intake of indicator PCBs.