ObjectiveTo explore the possible mechanism of action of Lifei Xiaoji Pill （理肺消积丸， LXP） in the treatment of non small cell lung cancer based on the Warburg effect and the USP47/BACH1 pathway. MethodsFifty C57BL/6 mice were randomly divided into five groups， model group， LXP group， inhibitor group， LXP + inhibitor group， and cisplatin group， with 10 mice in each group. A lung cancer mouse model was established by subcutaneously injecting Lewis cells. On the next day， the model group mice were given 0.2 ml of saline by gavage daily， the LXP group given 240 mg/（kg·d） of LXP solution once a day by gavage， the inhibitor group intraperitoneally injected with P22077 at a dose of 10 mg/（kg·d） every day， the LXP + inhibitor group given both LXP by gavage and P22077 by intraperitoneal injection once a day， and the cisplatin group received 0.5 mg/（kg·d） cisplatin intraperitoneally every other day. All treatments lasted for 14 days. On the day after the last dose， tumor weight and volume were measured， tumor histopathology was examined by HE staining， apoptosis in tumor tissues was detected by TUNEL staining， and proliferation cell nuclear antigen （PCNA） protein levels were detected by immunohistochemistry. Warburg effect indicators， including glucose concentration， lactate content， and adenosine triphosphate （ATP） production in tumor tissues， were measured. Western Blot and qRT-PCR were used to detect the protein and mRNA expression levels of USP47， BACH1， hexokinase 2 （HK2）， and glyceraldehyde 3-phosphate dehydrogenase （GAPDH）. ResultsCompared with the model group， all drug intervention groups showed reduced tumor weight and volume， improved tumor pathology， decreased PCNA positive rate， increased apoptosis rate， and reduced expression levels of USP47， BACH1， and HK2 proteins and mRNA （P＜0.05 or P＜0.01）. Except for lactate content in the cisplatin group， the glucose concentration in tumor tissues of other drug intervention groups increased， while lactate content and ATP production decreased （P＜0.05 or P＜0.01）. Compared with the LXP group， the LXP + inhibitor group showed more significant improvements in these indicators （P＜0.05 or P＜0.01）. Compared with the cisplatin group， the LXP + inhibitor group had lower mRNA expression of HK2 and GAPDH， and lower protein levels of USP47 and HK2 （P＜0.05 or P＜0.01）. Compared with the inhibitor group， the cisplatin group had higher HK2 protein levels， while the LXP + inhibitor group showed lower mRNA expression of BACH1， HK2， and GAPDH （P＜0.05 or P＜0.01）. ConclusionLXP significantly inhibits tumor growth in lung cancer mice， and its mechanism of action may be related to inhibiting the Warburg effect via the USP47/BACH1 pathway.

【Objective】 To investigate the development of adaptability in children aged 2 - 6, and to explore its influencing factors, so as to provide reference for promoting the development of adaptability in young children. 【Methods】 Data were from the National Nutrition and Health Systematic Survey for Children in China, and 3 319 children aged 2 - 6 and their parents from 28 sites across 14 provinces were recruited in this study.The Development Scale for Children Aged 0 - 6 years (WS/T 580-2017) was used to measure the developmental quotient of children′s adaptive ability, and a survey questionnaire was used to collect relevant information about children and their parents. 【Results】 Among 3 319 children aged 2 - 6, the proportion of slightly low or low level of adaptability, moderate adaptability development, good and excellent adaptability development was 7.68%,66.25% and 26.06%, respectively.The proportion of children aged 5 - 6 with good and excellent adaptability was lower in 3-year-old and 4-year-old groups (χ²=59.29, P<0.05).Multiple stepwise linear regression showed that children′s gender (β=0.06), gestational age of birth (β=-0.05), only child (β=-0.04), left-behind child (β=-0.04), the main caregiver (β=-0.06), and the education level of parents (β=0.09, 0.10), whether parents actively pay attention to children′s emotions (β=-0.06) and whether children play with homemade toys (β=-0.04) were the influencing factors of children′s adaptive development quotient.Girls, full-term children, only children, non-left-behind children, children with parents as main caregivers, parents with a high level of education, parents who often take the initiative to pay attention to children′s emotions, and children who play with homemade toys had a higher level of adaptability development quotient. 【Conclusions】 The development level of adaptability in children aged 2 - 6 in China is mostly above the average level and is related to multiple factors.Targeted intervention work can be carried out on relevant factors in order to promote the development of children′s adaptability.

Objective To investigate the role of lncSIL in transforming growth factor-β1(TGF-β1)-induced alveo-lar epithelial interstitial transformation(EMT)and its related signaling pathways.Methods Western blot was used to detect the effect of lncSIL silencing on the expression of E-cadherin(E-cad),alpha-smooth muscle actin(α-SMA)and Collagen I(Col I)in the process of EMT induced by TGF-β1.LncSIL interacting proteins were ana-lyzed by RNA pulldown.Western blot was used to detect the effect of overexpression or silencing of lncSIL on the expression of its target gene enhancer of zeste homolog 2(EZH2)and its downstream factors P21 and cyclin-de-pendent kinase 6(CDK6).Flow cytometry was used to analyze the effect of lncSIL on cell cycle progression.Re-sults After lncSIL silencing,the expression of α-SMA and Col I increased,the expression of E-cad decreased.RNA pulldown assay showed that EZH2 was the target protein that interacted with lncSIL,and the expression of EZH2 increased after silencing lncSIL,the expression of EZH2 downstream gene P21 decreased,CDK6 increased.Flow cytometry showed that the number of cells in S phase significantly increased.When lncSIL was overexpressed,the expression of EZH2 and CDK6 was down-regulated,the expression of P21 was up-regulated,and the number of S phase cells significantly decreased.Conclusion LncSIL inhibits TGF-β1-induced alveolar epithelial cell mesen-chymal transition by negatively regulating EZH2/P21/CDK6 signaling pathway to inhibit cell cycle progression.

Objective:To construct a novel cuproptosis-related gene signature (CRGS) for prediction of prognosis, immunotherapy response and drug sensitivity in patients with hepatocellular carcinoma (HCC).Methods:Data materials for this study were obtained from the international cancer genome consortium (ICGC), the cancer genome atlas (TCGA) database and Migort210 database, and protein expression profiles were obtained from the human protein atlas image classification database. Based on the TCGA cohort, the least absolute shrinkage and selection operator algorithm was applied to construct the CRGS and calculate the risk score for each HCC patient. HCC patients were grouped according to the median risk score: HCC patients in the TCGA cohort were divided into a high-risk group TCGA and a low-risk group TCGA with 184 cases in each group; HCC patients in the ICGC cohort were divided into a high-risk group ICGC and a low-risk group ICGC with 116 cases in each group. Patients in the Migort210 cohort were divided into a responder group ( n=68) and a non-responder group ( n=230) based on their response to immunotherapy. We assessed the value of CRGS in predicting the prognosis of HCC patients in the TCGA cohort and validated whether CRGS could be used to predict the prognosis of HCC patients in the ICGC dataset. To explore the role of CRGS in predicting immunotherapy response and drug sensitivity in HCC patients based on data from the TCGA cohort, and to apply the Migort210 immunotherapy cohort to validate the clinical value of CRGS in predicting immunotherapy in malignant tumors. Results:CRGS consists of four copper death-related genes: GLS, CDKN2A, LIPT1, and DLAT. Patients in the high-risk group TCGA had lower overall survival (OS), disease-specifical survival, and progression-free interval than those in the low-risk group TCGA (all P<0.01). OS of patients in the high-risk group ICGC was lower than that in the low-risk group ICGC ( P=0.022). Multivariate Cox regression analysis showed that CRGS was an independent risk factor for poor prognosis in HCC patients (TCGA: HR=2.991, 95% CI: 1.781-5.049, P<0.001; ICGC: HR=4.621, 95% CI: 1.685-12.674, P=0.033). Risk scores were positively correlated with the expression levels of CTLA4, PDCD1, CD80 and HLLA2 (all P<0.001). Patients in the high-risk group TCGA had lower tumor immune dysfunction and rejection scores than those in the low-risk group TCGA [-0.04(-0.07, -0.02) vs. -0.02(-0.04, 0) points], and the difference was statistically significant ( P<0.001). Patients in the responder group had a higher risk score than the non-responder group [1.70 (1.56, 1.90) vs. 1.63 (1.52, 1.80)], with a statistically significant difference ( P<0.05). The half-inhibitory concentrations (IC 50) for sunitinib, rapamycin and etanercept were higher in the high-risk group TCGA than that in the low-risk group TCGA, while the IC 50 for erlotinib was lower than that in the low-risk group TCGA, and the differences were all statistically significant (all P<0.001). Conclusion:The CRGS might be served as a potential biomarker to predict the prognoses, immunotherapy response, and drug sensitivity of patients with HCC.

Objective To observe the effect of transcutaneous electrical acupoint stimulation(TEAS)on circulation depression in patients underwent thoracoscopic radical resection of lung cancer under general anesthesia combined with thoracic paravertebral block(TPVB).Methods A total of 150 patients from Octomber 2021 to May 2022,58 males and 92 females,aged 19-64 years,BMI 18-30 kg/m2,ASA physical status Ⅰ or Ⅱ,underwent thoracoscopic radical resection of lung cancer under general anesthesia combined with TPVB were enrolled.According to random number table method,the patients were divided into two groups:the TEAS group and the control group,75 patients in each group.In the TEAS group,transcutaneous electrical acupoint stimulation was performed at Hegu,Neiguan,and Zusanli 30 minutes be-fore induction until the end of operation.In the control group,the electrodes were only connected at the same time point without electrical stimulation.HR,SBP,DBP,MAP,and BIS were recorded before stimu-lation(T0),10 minutes after TPVB(T1),the time of skin incision(T2),30 minutes after operation star-ted(T3),60 minutes after operation started(T4),the end of operation(T5),and 30 minutes after opera-tion(T6).The incidences of bradycardia,tachycardia,hypotension,and hypertension,and the usages of vasoactive drugs during operation were recorded.The dosages of propofol,sufentanil,and remifentanil in the operation were recorded.The VAS pain score 1,2,and 7 days after operation,the usages of analgesics used within 7 days after operation,postoperative adverse effects such as nausea and vomiting,dizziness,chest tightness,and shortness of breath,and the length of hospital stay were recorded.Results Compared with the control group,intraoperative infusion volume,incidence of hypotension,hypertension,and circulation depression,the usages of deoxyepinephrine,ephedrine,norepinephrine,and urapidil intraoperation,VAS pain scores 1 and 2 days after operation,and the usage of analgesics within 7 days after operation were sig-nificantly decreased(P＜0.05),length of hospital stay was significantly shortened(P＜0.05),SBP,DBP,and MAP were significantly increased at T1(P＜0.05),the dosagesof propofol,sufentanil,and remifentanil were significantly decreased in the TEAS group(P＜0.05).There were no significantly differ-ences of nausea and vomiting,dizziness,and shortness of breath between the two groups.Conclusion TEAS can improve the circulation depression,and reduce the incidences of intraoperative hypotension and hypertension,decrease the dosages of anesthetics and the rate of using vasoactive drugs during operation,improve early postoperative acute pain and shorten the length of hospital stay in patients undergoing thoraco-scopic radical resection of lung cancer under general anesthesia combined with TPVB.

Objective: To explore the association between mobile phone dependence and constipation of college students in Yunnan Province, and to provide a data reference for improving and preventing constipation in college students. Methods: A questionnaire survey was conducted among 9 960 college students from three universities in Kunming and Dali, Yunnan Province. The Self rating Questionnaire for Adolescent Problematic Mobile Phone Use was used to assess mobile phone dependence symptoms, and the questionnaire was conducted to collect the constipation information of college students. Data were analyzed with SPSS 23.0. Chi square test was used to compare the reporting rates of detection in college students with different demographic characteristics. The association between mobile phone dependence and constipation was analyzed by binary Logistic regression models. Results: The detection rate of mobile phone dependence symptoms was 30.93%, and the reporting rates of constipation was 24.46% of college students in Yunnan Province. After collcted for the demographic variables and other confounding effects, the analysis results showed that:withdrawal symptoms of mobile phone dependence( OR=1.29, 95%CI =1.09-1.54), physical and mental health impacts of mobile phone dependence ( OR=1.25, 95%CI =1.10-1.43) and craving of mobile phone dependence ( OR=1.20, 95%CI =1.06-1.36) were associated with constipation in college students( P <0.01). Conclusion Mobile phone dependence may increase the risk of constipation of college students in Yunnan Province, so health education should be strengthend.

The tea beverages will be endowed with distinct aroma and taste, as well as various biologically active compounds including probiotic factors, when fermented with lactic acid bacteria (LAB). However, at present, few studies on the dynamics of flavors in tea soup at different fermentation stages were conducted. In this study, the composition of monosaccharides, aromatic components, free amino acids, and organic acids were measured, when the black tea beverages were fermented with Lactobacillus coryniformis FZU63 which was isolated from Chinese traditional kimchi. The results indicated that monosaccharides including glucose, fructose, mannose and xylose in black tea beverages are the main carbon sources for fermentation. In addition, the abundance of aromatic compounds in black tea soup are increased significantly at different fermentation stages, which endow the fermented black tea soup with fruit aroma on the basis of flowery and nutty aroma. Moreover, some bitter amino acids are reduced, whereas the content of sweet and tasty amino acids is elevated. Furthermore, the levels of lactic acid, malic acid, citric acid and other organic acids are accumulated during the fermentation. Additionally, sensory evaluation displays that black tea beverage is acquired with comprehensive high-quality after being fermented for 48 h. This study provides a theoretical basis to steer and control the flavor formation and quality of the fermented tea beverages during LAB fermentation.
Tea/chemistry* ; Beverages/microbiology* ; Camellia sinensis ; Fermentation ; Acids ; Amino Acids ; Glucose

Objective:To observe the morphological characteristics of urogenital hiatus in patients with gestational diabetes mellitus (GDM) after vaginal delivery.Methods:This study included 192 pregnant patients from Henan Provincial People′s Hospital who met the conditions between Jan.2020 and Aug.2021. All participants were screened for GDM by oral glucose tolerance test (OGTT) or fasting blood glucose at 24-28 weeks of pregnancy, and were divided into GDM group (34 cases) and non-GDM group (158 cases) based on the presence or absence of GDM. All participants underwent pelvic floor ultrasonography at the first trimester (6-8 gestational weeks), 3 days postpartum, 6 weeks postpartum, 6 months postpartum, and 1 year postpartum. Area of urogenital hiatus (AUH), transversal diameter of urogenital hiatus (TDUH) and anteroposterior diameter of urogenital hiatus (APDUH) were measured using Smart Pelvic. The Logistic regression model was used to calculate and match the propensity score between the GDM group and the non-GDM group.Results:In the non-GDM group, TDUH during rest maneuver at 6 weeks postpartum( P=0.319), the indicators during rest and contract maneuver at 6 months postpartum( P=0.586, 0.877, 0.164, 0.226, 0.465, 0.097), and TDUH during tension maneuver at 1 year postpartum( P=0.643) returned to the level of early pregnancy. In the GDM group, the indicators during rest maneuver and TDUH during contract maneuver at 6 months postpartum recovered to the level of early pregnancy ( P=0.647, 0.584, 0.376, 0.440), while APDUH and AUH during contract maneuver ( F=7.784, 9.785; P=0.005, <0.001) and the indicators during tension maneuver at 1 year postpartum( F=15.343, 11.974, 17.981; P<0.001) did not recover to the level of early pregnancy. After propensity score matching, APDUH and AUH during tension maneuver at 1 year postpartum in the GDM group were significantly greater than those in the non-GDM group( t=2.810, 2.926; P=0.006, 0.004). Conclusions:The pelvic floor muscles of GDM patients after vaginal delivery are more severely damaged, and the recovery speed is slower. Pelvic floor muscle exercise during pregnancy and enhanced postpartum follow-up are needed to prevent, diagnose and treat pelvic floor dysfunction early.

Objective: To explore the relationship between anemia and neuropsychological development in various domains among preschool children in China. Methods: Data came from the National Nutrition and Health Systematic Survey for children in China, and 3 261 preschool children aged 2-6 years and their parents from 28 sites across 14 provinces were recruited in this study. Parental and child characteristics were obtained by interview administrated questionnaires. Blood hemoglobin(Hb) concentration was determined by Hemocue method. Neuropsychological development quotients were assessed using the Development Scale for Children Aged 0-6 Years(WS/T 580-2017). Results: The average Hb level was (125.23±11.49)g/L and the overall anemia prevalence was 10.30% among preschool children. After adjusting the confounding factors(sex, age, ethnicity, region, feeding mode, maternal status during pregnancy, etc), developmental quotients of gross motor( β=-2.15, 95%CI =-3.89--0.41), fine motor( β=-2.46, 95%CI =-4.12--0.79), adaptive behavior( β=-2.59, 95%CI =-4.42--0.76), language( β=-3.65, 95%CI =-5.53--1.78), personal social behavior( β=-3.11, 95%CI =-4.94--1.28) and full scale( β=-2.79, 95%CI =-4.10--1.49) among children with anemia were significantly lower than non anemic infants( P <0.05). Conclusion Anemia was negatively associated with developmental quotient, as well as five domains of gross motor, fine motor, adaptive behavior, language, and personal social behavior in preschool children aged 2-6 years. It is suggested to carry out the work of anemia monitoring and intervention in preschool children to further improve their neuropsychological development.

Purpose: Ischemic brain injury results in high mortality and serious neurologic morbidity. Here, we explored the role of SNHG15 in modulating neuronal damage and microglial inflammation after ischemia stroke. Materials and Methods: The hypoxia/ischemia models were induced by middle cerebral artery occlusion in mice and oxygenglucose deprivation/reoxygenation (OGD/R) in vitro. Quantitative real-time PCR (qRT-PCR) and Western blot were conducted to determine the levels of SNHG15, miR-302a-3p, and STAT1/NF-κB. Moreover, gain- or loss-of functional assays of SNHG15 and miR-302a-3p were conducted. MTT assay was used to evaluate the viability of HT22 cells, and the apoptotic level was determined by flow cytometry. Furthermore, enzyme-linked immunosorbent assay was performed to detect oxidative stress and inflammatory mediators in the ischemia cortex and OGD/R-treated BV2 microglia. Results: The SNHG15 and STAT1/NF-κB pathways were both distinctly up-regulated, while miR-302a-3p was notably down-regulated in the ischemia cortex. Additionally, overexpressing SNHG15 dramatically enhanced OGD/R-mediated neuronal apoptosis as well as the expression of oxidative stress and inflammation factors from microglia. In contrast, knocking down SNHG15 or overexpressing miR-302a-3p relieved OGD/R-mediated neuronal apoptosis and microglial activation. Moreover, the rescue experiment testified that overexpressing miR-302a-3p also attenuated SNHG15 up-regulation-induced effects. In terms of the mechanisms, SNHG15 sponged miR-302a-3p and activated STAT1/NF-κB as a competitive endogenous RNA, while miR-302a-3p targeted STAT1 and negatively regulated the STAT1/NF-κB pathway. Conclusion SNHG15 was up-regulated in the hypoxia/ischemia mouse or cell model. The inhibition of SNHG15 ameliorates ischemia/hypoxia-induced neuronal damage and microglial inflammation by regulating the miR-302a-3p/STAT1/NF-κB pathway.