Objective:To investigate the risk factors of bronchopulmonary dysplasia (BPD) in very low birth weight (VLBW) infants with gestational age ≤32 weeks within 28 days after birth and to establish and validate the nomogram model for BPD prediction.Methods:We retrospectively chose VLBW infants with gestational age ≤32 weeks who survived to postmenstrual age (PMA) 36 weeks and were admitted to the neonatal intensive care unit of Peking University Third Hospital from January 2016 to April 2020 as the training cohort. BPD was diagnosed in accordance with the 2018 criteria. The clinical data of these infants were collected, and the risk factors of BPD were analyzed by Chi-square test, Mann-Whitney U test, and multivariate logistic regression, and a nomogram model was established. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used to assess the predictive performance. Decision curve analysis (DCA) was constructed for differentiation evaluation, and the calibration chart and Hosmer-Lemeshow goodness of fit test were used for the calibration evaluation. Bootstrap was used for internal validation. VLBW infants with gestational age ≤32 weeks survived to PMA 36 weeks and admitted to Hebei Chengde Maternal and Child Health Hospital from October 2017 to February 2022 were included as the validation cohort. ROC curve and calibration plot were conducted in the validation cohort for external validation. Results:Of the 467 premature infants included in the training cohort, 104 were in the BPD group; of the 101 patients in the external validation cohort, 16 were in the BPD group. Multivariate logistic regression analysis showed that low birth weight ( OR=0.03, 95% CI: 0.01-0.13), nosocomial pneumonia ( OR=2.40, 95% CI: 1.41-4.09), late-onset sepsis ( OR=2.18, 95% CI: 1.18-4.02), and prolonged duration of endotracheal intubation ( OR=1.61, 95% CI: 1.26-2.04) were risk factors for BPD in these groups of infants (all P<0.05). According to the multivariate logistic regression analysis results, a nomogram model for predicting BPD risk was established. The AUC of the training cohort was 0.827 (95% CI: 0.783-0.872), and the ideal cut-off value for predicted probability was 0.206, with a sensitivity of 0.788 (95% CI: 0.697-0.862) and specificity of 0.744 (95% CI: 0.696-0.788). The AUC of the validation cohort was 0.951 (95% CI:0.904-0.999). Taking the prediction probability of 0.206 as the high-risk threshold, the sensitivity and specificity corresponding to this value were 0.812 (95% CI: 0.537-0.950) and 0.882 (95% CI: 0.790-0.939). The Hosmer-Lemeshow goodness-of-fit test in the training and validation cohort showed a good fit ( P>0.05). DCA results showed a high net benefit of clinical intervention in very preterm infants when the threshold probability was 5%~80% for the training cohort. Conclusion:Low birth weight, nosocomial pneumonia, late-onset sepsis, and prolonged tracheal intubation duration are risk factors for BPD. The established nomogram model has a certain value in predicting the risk of BPD in VLBW less than 32 weeks.

Objective:To explore any effects of combining virtual reality training with aromatherapy in caring for Alzheimer′s disease patients in a nursing home.Methods:Fifty nursing home residents with Alzheimer′s were divided at random into an observation group and a control group, each of 25. Both groups received routine rehabilitation, while the observation group was additionally given 45 minutes of virtual reality training combined with aromatherapy, 3 times a week for 6 months. Both groups′ cognition was then evaluated using the MMSE and an Alzheimer′s cognition assessment scale (ADAS-cog). Psycho-behavioral symptoms were quantified using the Alzheimer′s disease pathological behavior scale (BEHAVE-AD). Motor functioning was quantified using the timed up and go test (TUGT), the 30-second sit-to-stand test (30sCST), the 30-second arm curl test (30sACT) and the sit-and-reach test (CSRT). Ability in the activities of daily living (ADL) and life quality were quantified using the activity of daily living scale and of the quality of life scale for Alzheimer′s disease (QOL-AD) before and after the intervention.Results:After the intervention the average MMSE, ADAS-cog, BEHAVE-AD and ADL scores of both groups had improved significantly, with the average improvement in the observation group significantly greater than that in the control group. The TUGT, 30sCST, 30sACT and CSRT results of both groups were also significantly better, with those of the observation group again significantly superior, on average, to the control group′s results. The average QOL-AD score in the observation was significantly improved after the intervention, and was then significantly better than the control group′s average.Conclusions:Virtual reality training combined with aromatherapy can significantly improve the cognition, psycho-behavioral symptoms, activity in daily living, motor functioning and life quality of Alzheimer′s patients in a nursing home. It is worthy of promotion and application in nursing homes.

Objective:To observe any effect of virtual reality (VR) training on the cognitive functioning and functional fitness of nursing home residents with subjective cognitive decline (SCD).Methods:Fifty-six of such residents were randomly divided into an observation group and a control group, each of 28. Both groups received health education and routine care, but the observation group was additionally provided with 45 minutes of VR training three times a week for 6 months. The training included Baduanjin, magic, flying bird, supermarket shopping, gravity ball and gym episodes. Both groups′ cognition was evaluated using the subjective cognitive decline questionnaire (SCD-Q), the Montreal cognitive assessment (MoCA), the Rivermead Behavioural Memory Test (second edition) (RBMT-Ⅱ), a digit symbol substitution test (DSST), an animal fluency test (AFT) and trail-making test A-B (TMT A-B). Functional fitness was quantified using the 8-foot up-and-go test (8UGT), a 30-second arm curl test (30sACT), a 30-second chair stand test (30sCST), a back scratching test (BST), the sit-and-reach test (CSRT) and a 2-minute step test (2MST) before and after the 6-month intervention.Results:After the intervention, the average SCD-Q, MoCA, RBMT-Ⅱ, DSST, TMT-A, and TMT-B scores of the observation group were significantly better than before the intervention, and significantly better than the control group′s averages. And except for the back scratching their functional results were also significantly better, on average, than those of the control group.Conclusions:VR training can effectively improve the cognition and functional fitness of nur-sing home residents with SCD. Such training is worthy of promotion and wider application in nursing homes.

Increasing evidences suggest the important role of calcium homeostasis in hallmarks of cancer, but its function and regulatory network in metastasis remain unclear. A comprehensive investigation of key regulators in cancer metastasis is urgently needed. Transcriptome sequencing (RNA-seq) of primary esophageal squamous cell carcinoma (ESCC) and matched metastatic tissues and a series of gain/loss-of-function experiments identified potassium channel tetramerization domain containing 4 (KCTD4) as a driver of cancer metastasis. KCTD4 expression was found upregulated in metastatic ESCC. High KCTD4 expression is associated with poor prognosis in patients with ESCC and contributes to cancer metastasis in vitro and in vivo. Mechanistically, KCTD4 binds to CLIC1 and disrupts its dimerization, thus increasing intracellular Ca²⁺ level to enhance NFATc1-dependent fibronectin transcription. KCTD4-induced fibronectin secretion activates fibroblasts in a paracrine manner, which in turn promotes cancer cell invasion via MMP24 signaling as positive feedback. Furthermore, a lead compound K279-0738 significantly suppresses cancer metastasis by targeting the KCTD4‒CLIC1 interaction, providing a potential therapeutic strategy. Taken together, our study not only uncovers KCTD4 as a regulator of calcium homeostasis, but also reveals KCTD4/CLIC1-Ca²⁺-NFATc1-fibronectin signaling as a novel mechanism of cancer metastasis. These findings validate KCTD4 as a potential prognostic biomarker and therapeutic target for ESCC.

Objective To study the composition and concentration of atmospheric particulate pollutants in four seasons in the industrial and clean living areas， and to provide a scientific basis for the strategy of controlling industrial pollution and atmospheric environment. Methods An industrial area dominated by the automobile industry in Shanghai and a relatively clean living area were selected. Samples were collected simultaneously in both areas and continuously for 7 days in the middle of each season. The composition and concentration of PM_2.5 were determined， and the ecological risk of heavy metals in PM_2.5 was evaluated by the potential ecological risk index method. Results We found PM_2.5 concentration was associated with seasonal changes. The PM_2.5 concentration in living areas was the highest in winter， followed by spring， and the lowest in summer. The PM_2.5 concentration in industrial areas was the highest in spring， followed by winter， and the lowest in summer. The heavy metals in PM_2.5 were the same， including Al， Cr， Mn， Ni， As， Cd， Hg and Pb. The content of Cr， Cd and Pb in PM_2.5 in the industrial area is significantly higher than that in the living area. The potential ecological hazard coefficient of PM_2.5 heavy metal Cd in the industrial zone was the highest， up to 189.47， and it was the main component of the total potential ecological hazard index of heavy metals. According to the total potential risk grade of heavy metals， the heavy metal Cd in the industrial area had different degrees of ecological harm with seasonal changes. The ecological harm degree of heavy metal Cd was the highest in winter， high in spring and autumn， and low in summer. Conclusion Although the concentration of PM_2.5 in the industrial area is not higher than that in the living area， the content of Cr， Cd and Pb in the PM_2.5 in the industrial area is significantly higher than that in the living area. The concentration of PM_2.5 in the industrial area is mainly related to seasons， industrial production and human factors. The potential ecological harm coefficient of heavy metal Cd in PM_2.5 is the highest in comparison with other heavy metals such as Cr， Hg and Pb， and it is the main component of the total potential ecological harm index ofheavy metals.

Objective: Endometrial cancer (ECa) is a common gynecological malignancy. Circular RNAs (circRNAs) have been identified as key regulators of human tumorigenesis and development. Herein, we explored the role and mechanism of circular RNA intraflagellar transport 80 (circ-IFT80, also called circ_0067835) in ECa. Methods: Circ-IFT80, microRNA-545-3p (miR-545-3p), and family with sequence similarity 98 member A (FAM98A) were quantified by quantitative real-time polymerase chain reaction or Western blot. The biological characteristics of ECa cells were evaluated via Cell Counting Kit-8, 5-ethynyl-2′-deoxyuridine, transwell, tube formation and flow cytometry assays. Dual-luciferase reporter assay or RNA pull-down assay was employed to verify the binding relationship between miR-545-3p and circ-IFT80 or FAM98A. Xenograft assays were conducted to analyze the effect of circ-IFT80 in vivo. Results: Circ-IFT80 and FAM98A were up-regulated, and miR-545-3p was down-regulated in ECa tissues and cells. Knockdown of circ-IFT80 blocked proliferation, migration, invasion and angiogenesis and promoted apoptosis in ECa cells. Moreover, circ-IFT80 harbored a binding site for miR-545-3p, and the effects of circ-IFT80 were mediated by miR-545-3p. FAM98A was a direct target of miR-545-3p, and miR-545-3p hindered ECa cell progression via targeting FAM98A. Circ-IFT80 induced FAM98A expression through miR-545-3p. Furthermore, silence of circ-IFT80 suppressed tumor growth in vivo. Conclusion Circ-IFT80 may promote the malignant progression of ECa cells at least in part by modulating miR-545-3p/FAM98A axis, providing a potential therapeutic target for ECa.

Lnc-HUR1 is an HBV-related long non-coding RNA, which can promote the proliferation of hepatoma cells and the occurrence and development of liver cancer. In this study we explored the effect of lnc-HUR1 on the apoptosis of hepatocellular carcinoma cells by taking the approach of immunoblotting, quantitative real time PCR, luciferase reporter assay, chromatin immunoprecipitation (ChIP) and flow cytometry. We found that overexpression of lnc-HUR1 significantly reduced the activity of caspase3/7 and the cleavage of PARP-1, while knocking down of lnc-HUR1 significantly increased the activity of caspase3/7 and promoted the cleavage of PARP-1 in HepG2 cells treated with TGF-β, pentafluorouracil or staurosporine. Consistently, the data from Annexin-V/PI staining showed that overexpression of lnc-HUR1 inhibited apoptosis, while knockdown of lnc-HUR1 promoted apoptosis. Moreover, overexpression of lnc-HUR1 up-regulated the apoptosis inhibitor Bcl-2 and down-regulated the pro-apoptotic factor BAX at both RNA and protein levels. In the CCL4-induced acute liver injury mice model, the expression of Bcl-2 in the liver tissue of lnc-HUR1 transgenic mice was higher than that of the control mice. The data from ChIP assay indicated that lnc-HUR1 reduced the enrichment of p53 on Bcl-2 and BAX promoters. All these results indicated that lnc-HUR1 inhibited the apoptosis by promoting the expression of apoptosis inhibitor Bcl-2 and inhibiting the expression of apoptosis promoting factor BAX. Further studies showed that lnc-HUR1 regulated the transcription of Bcl-2 and BAX in HCT116 cells, but had no effect on the expression of Bcl-2 and BAX in HCT116 p53^-/- cells, indicating that lnc-HUR1 regulates the transcription of Bcl-2 and BAX dependent upon the activity of p53. In conclusion, HBV upregulated lnc-HUR1 can inhibit the apoptosis of hepatoma cells. Lnc-HUR1 inhibits apoptosis by inhibiting the transcriptional activity of p53. These results suggest that lnc-HUR1 plays an important role in the occurrence and development of HBV-related hepatocellular carcinoma.
Animals ; Annexins/pharmacology* ; Apoptosis ; Carcinoma, Hepatocellular/genetics* ; Cell Proliferation ; Hep G2 Cells ; Hepatitis B virus/metabolism* ; Humans ; Liver Neoplasms/genetics* ; Mice ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology* ; Proto-Oncogene Proteins c-bcl-2/pharmacology* ; RNA, Long Noncoding/metabolism* ; Staurosporine/pharmacology* ; Transforming Growth Factor beta/pharmacology* ; Tumor Suppressor Protein p53/pharmacology* ; bcl-2-Associated X Protein/pharmacology*

Objective:To analyze the risk factors of bronchopulmonary dysplasia(BPD)in very preterm infants(VPI), and to provide scientific basis for the prevention and treatment of BPD in VPI.Methods:A prospective multicenter study was designed to collect the clinical data of VPI in department of neonatology of 28 hospitals in 7 regions from September 2019 to December 2020.According to the continuous oxygen dependence at 28 days after birth, VPI were divided into non BPD group and BPD group, and the risk factors of BPD in VPI were analyzed.Results:A total of 2 514 cases of VPI including 1 364 cases without BPD and 1 150 cases with BPD were enrolled.The incidence of BPD was 45.7%.The smaller the gestational age and weight, the higher the incidence of BPD( P<0.001). Compared with non BPD group, the average birth age, weight and cesarean section rate in BPD group were lower, and the incidence of male infants, small for gestational age and 5-minute apgar score≤7 were higher( P<0.01). In BPD group, the incidences of neonatal respiratory distress syndrome(NRDS), hemodynamically significant patent ductus arteriosus, retinopathy of prematurity, feeding intolerance, extrauterine growth restriction, grade Ⅲ~Ⅳ intracranial hemorrhage, anemia, early-onset and late-onset sepsis, nosocomial infection, parenteral nutrition-associated cholestasis were higher( P<0.05), the use of pulmonary surfactant(PS), postnatal hormone exposure, anemia and blood transfusion were also higher, and the time of invasive and non-invasive mechanical ventilation, oxygen use and total hospital stay were longer( P<0.001). The time of starting enteral nutrition, cumulative fasting days, days of reaching total enteral nutrition, days of continuous parenteral nutrition, days of reaching 110 kcal/(kg·d) total calorie, days of reaching 110 kcal/(kg·d) oral calorie were longer and the breastfeeding rate was lower in BPD group than those in non BPD group( P<0.001). The cumulative doses of amino acid and fat emulsion during the first week of hospitalization were higher in BPD group( P<0.001). Multivariate Logistic regression analysis showed that NRDS, invasive mechanical ventilation, age of reaching total enteral nutrition, anemia and blood transfusion were the independent risk factors for BPD in VPI, and older gestational age was the protective factor for BPD. Conclusion:Strengthening perinatal management, avoiding premature delivery and severe NRDS, shortening the time of invasive mechanical ventilation, paying attention to enteral nutrition management, reaching whole intestinal feeding as soon as possible, and strictly mastering the indications of blood transfusion are very important to reduce the incidence of BPD in VPI.

Objective:To investigate the effects of asymmetric trans-sutural distraction osteogenesis for severe midfacial hypoplasia in growing patients with unilateral cleft lip and palate.Methods:All the growing patients with unilateral cleft lip and palate combining severe midfacial hypoplasia treated with asymmetric trans-sutural distraction osteogenesis from January 2011 to December 2020 in the Plastic Surgery Hospital, Chinese Academy of Medical Sciences were analyzed retrospectively. The distraction system consisted of the bone-borne traction hooks, nickel-titanium shape memory alloy spring and rigid external distractor. Asymmtric distraction could be achieved by exerting different traction force to bilateral maxilla. The technique for relapse prevention included moderate overcorrection, prompt orthodontic treatment and face mask therapy. The changes of midfacial symmetry between the cleft and non-cleft side were analyzed by comparing the distance of subspinale A-point(A), intersection of lateral border of piriform aperture and plane parallel to midsagittal reference plane(LPA), most inferior point on nasomaxillary suture(INM) and most inferior point on profile of pterygomaxillary suture(PTM) to coronal reference plane between preoperative and postoperative, and the asymmetric ratio of LPA, INM and PTM were calculated.Results:A total of 38 patients, (34 males and 4 females, aged from 8-15 years) were included. All of the patients completed the distraction and achieved a satisfied improvement in the midface convexity and overjet. The postoperative 1-3 years follow-up showed the midface protrusion and occlusal overcoverage after distraction caused by overcorrection tended to become harmonious in the following 6 to 12 months, and 3 patients with no face mask therapy done had relapse on maxilla in various degrees after 3 years follow-up. The measurement findings of 25 patients showed the average advancement of A point was (12.67±4.62) mm(range, 6.21-23.28 mm). The distances of INM, LPA and PTM to CR plane on the cleft side were significantly less than that on the non-cleft side before the distraction( P<0.05). However, after the distraction, these distance differences of INM and PTM between the cleft and non-cleft side were eliminated ( P>0.05). The distance difference of bilateral LPA was reduced, but still significant less on the cleft side( P<0.05). Compared before and after distraction, the asymmetric rate of INM, LPA and PTM was significantly decreased( P<0.05). Conclusions:Asymmetric trans-sutural distraction osteogenesis offers an effective method for the early treatment of severe midfacial hypoplasia in growing patients with unilateral cleft lip and palate, and restores the midfacial symmetry.

Objective:To investigate the effects of asymmetric trans-sutural distraction osteogenesis for severe midfacial hypoplasia in growing patients with unilateral cleft lip and palate.Methods:All the growing patients with unilateral cleft lip and palate combining severe midfacial hypoplasia treated with asymmetric trans-sutural distraction osteogenesis from January 2011 to December 2020 in the Plastic Surgery Hospital, Chinese Academy of Medical Sciences were analyzed retrospectively. The distraction system consisted of the bone-borne traction hooks, nickel-titanium shape memory alloy spring and rigid external distractor. Asymmtric distraction could be achieved by exerting different traction force to bilateral maxilla. The technique for relapse prevention included moderate overcorrection, prompt orthodontic treatment and face mask therapy. The changes of midfacial symmetry between the cleft and non-cleft side were analyzed by comparing the distance of subspinale A-point(A), intersection of lateral border of piriform aperture and plane parallel to midsagittal reference plane(LPA), most inferior point on nasomaxillary suture(INM) and most inferior point on profile of pterygomaxillary suture(PTM) to coronal reference plane between preoperative and postoperative, and the asymmetric ratio of LPA, INM and PTM were calculated.Results:A total of 38 patients, (34 males and 4 females, aged from 8-15 years) were included. All of the patients completed the distraction and achieved a satisfied improvement in the midface convexity and overjet. The postoperative 1-3 years follow-up showed the midface protrusion and occlusal overcoverage after distraction caused by overcorrection tended to become harmonious in the following 6 to 12 months, and 3 patients with no face mask therapy done had relapse on maxilla in various degrees after 3 years follow-up. The measurement findings of 25 patients showed the average advancement of A point was (12.67±4.62) mm(range, 6.21-23.28 mm). The distances of INM, LPA and PTM to CR plane on the cleft side were significantly less than that on the non-cleft side before the distraction( P<0.05). However, after the distraction, these distance differences of INM and PTM between the cleft and non-cleft side were eliminated ( P>0.05). The distance difference of bilateral LPA was reduced, but still significant less on the cleft side( P<0.05). Compared before and after distraction, the asymmetric rate of INM, LPA and PTM was significantly decreased( P<0.05). Conclusions:Asymmetric trans-sutural distraction osteogenesis offers an effective method for the early treatment of severe midfacial hypoplasia in growing patients with unilateral cleft lip and palate, and restores the midfacial symmetry.