Identification of pyruvic and maleic acid as potential markers for disease activity and prognosis in chronic urticaria.

BACKGROUND: Population-based studies have highlighted the link between chronic urticaria (CU) and metabolic syndrome, and metabolic alterations have been revealed in CU. However, to our knowledge, a comprehensive metabolomics study on a large cohort of patients with CU has not been reported. OBJECTIVE: We sought to explore the underlying metabolic subtypes and novel metabolite biomarkers for CU diagnosis and therapy. METHODS: Plasma samples from 80 patients with CU and 82 healthy controls were collected for metabolomics quantification and bioinformatics analysis. Another independent cohort consisting of 144 patients with CU was studied to validate the findings. Bone marrow-derived mast cells and mice with IgE-induced passive cutaneous anaphylaxis were used for in vitro and in vivo experiments, respectively. RESULTS: We observed clear metabolome differences between CU patients and healthy controls. Meanwhile, differential metabolites N6-acetyl-l-lysine, l-aspartate, maleic acid, and pyruvic acid were used to construct random forest classifiers and achieved area under receiver operating characteristic curve values greater than 0.85, suggesting their potential as diagnostic biomarkers of CU. More importantly, by exploring the underlying metabolic subtypes of CU, we found that the low abundance of pyruvic acid and maleic acid was significantly related to the activity of CU, poor efficacy of second-generation H1 antihistamines, and short relapse-free time. The results were validated in the independent cohort. Moreover, supplementation with pyruvate or maleate could significantly attenuate IgE-mediated mast cell activation in vitro and in vivo. CONCLUSIONS: Plasma pyruvic acid and maleic acid may be effective biomarkers for predicting disease activity, therapeutic efficacy, and prognosis for patients with CU.

A comparison of childbirth self-efficacy, fear of childbirth, and labor pain intensity between primiparas and multiparas during the latent phase of labor: a cross-sectional study.

BACKGROUND: Childbirth is a long-lasting physiological stress. As one of the main stressors, labor pain exists throughout the whole process. Childbirth self-efficacy is the confidence, or belief that they can manage pain during childbirth. This sense of self-efficacy determines how pregnant women deal with labor pain and enables them to regulate their behavior and actively deal with childbirth. However, the difference in pain sensitivity between single births (primiparas) and multiple births (multiparas) has rarely been investigated. OBJECTIVES: This study is aimed at investigating self-efficacy, fear of childbirth, labor pain of primiparas and multiparas and exploring factors related to the perceived labor pain intensity of pregnant women. DESIGN: Prospective cross-sectional study. SETTING(S): Labour and delivery in a large academic specialized hospital in Guangzhou, China. PARTICIPANTS: A total of 347 women, (182 primiparas and 165 multiparas) were enrolled in the data analysis. Pain was assessed before cervical dilatation (cervical dilatation ≤ 3 cm for the first delivery and ≤ 2 cm for the second delivery). METHOD: The general information of participants was obtained by questionnaire and obstetrical records of the subjects were obtained from the electronic medical records extracted from the electronic medical record system (EMRS). Childbirth self-efficacy, fear of childbirth (FOC) and labor pain were compared between primiparas and multiparas. Paired t-test, chi-square test, Mann-Whitney test, univariate and multivariate regression analysis were used to analyze labor pain between the two groups and investigate factors related perceived labor pain intensity. RESULTS: The total scores related to fear of childbirth, fetal health, self-control, and labor pain injury of multiparas were notably reduced compared with primiparas (all P < 0.05). The perceived labor pain intensity and duration of the first stage of labor was reduced in the multipara group compared with the primipara group. The childbirth control sense of the multipara was better than that of the primipara. The perceived labor pain intensity was negatively correlated with advanced age (age ≥ 35 years), self-efficacy score, family support, and education (all P < 0.05). In contrast, the perceived labor pain intensity was positively correlated with tension, severe fear of childbirth, and anxiety (P < 0.05). Self-efficacy, gravidity, delivery cognition, and fear of childbirth were independent risk factors for the perceived labor pain intensity in the latent period (all P < 0.05). CONCLUSIONS: Fear of childbirth is a predictor of perceived labor pain intensity. The extent of labor pain (minimum and maximum) can be predicted by the level of fear the expectant mother has. During the latent phase of labor, self-efficacy, fear of childbirth and labor pain are different between primiparas and multiparas.

Impact of closed-off management due to COVID-19 rebound on maternal depression during pregnancy.

BACKGROUND: This study aimed to assess the impacts of closed-off measures with different strictness levels (lockdown, partial lockdown and non-lockdown) and geographic proximity to patients with coronavirus disease 2019 (COVID-19) on prenatal depression during an epidemic rebound of COVID-19. METHODS: This was a cross-sectional web-based survey including 880 pregnant women. Depressive symptoms were measured by Self-Rating Depression Scale (SDS) and geographic proximity was calculated using Geographic Information Systems. Linear and logistic regression were used to assess the associations of closed-off measures and geographic proximity with SDS scores and depressive symptoms. Restricted cubic splines were used to model non-linear associations between geographic proximity and depression symptoms. RESULTS: Compared with those living in non-lockdown areas, women in lockdown areas had higher SDS scores (adjusted ß: 3.51, 95% CI: 1.80, 5.21) and greater risk of depressive symptoms (adjusted OR: 4.00, 95% CI: 2.18, 7.35), but evidence for partial lockdown was not obvious. A progressive increase in the risk of depressive symptoms was found with decreasing distance to COVID-19 patients when geographic proximity was <8 kilometers. Compared to those in the 5th quintile of geographic proximity, women in the first, second and third quintiles had at least 6 times higher risk of depressive symptoms. CONCLUSIONS: Pregnant women under strict closed-off management during COVID-19 epidemic have high risk of depression. A specific range around the residences of reported COVID-19 patients should be underlined as potential clustering of high prenatal depression levels. Our findings highlight the importance of enhancing mental health management during the COVID-19 epidemic for pregnant women.

Enhancing Patient Safety Through an Integrated Internet of Things Patient Care System: Large Quasi-Experimental Study on Fall Prevention.

BACKGROUND: The challenge of preventing in-patient falls remains one of the most critical concerns in health care. OBJECTIVE: This study aims to investigate the effect of an integrated Internet of Things (IoT) smart patient care system on fall prevention. METHODS: A quasi-experimental study design is used. The smart patient care system is an integrated IoT system combining a motion-sensing mattress for bed-exit detection, specifying different types of patient calls, integrating a health care staff scheduling system, and allowing health care staff to receive and respond to alarms via mobile devices. Unadjusted and adjusted logistic regression models were used to investigate the relationship between the use of the IoT system and bedside falls compared with a traditional patient care system. RESULTS: In total, 1300 patients were recruited from a medical center in Taiwan. The IoT patient care system detected an average of 13.5 potential falls per day without any false alarms, whereas the traditional system issued about 11 bed-exit alarms daily, with approximately 4 being false, effectively identifying 7 potential falls. The bedside fall incidence during hospitalization was 1.2% (n=8) in the traditional patient care system ward and 0.1% (n=1) in the smart ward. We found that the likelihood of bedside falls in wards with the IoT system was reduced by 88% (odds ratio 0.12, 95% CI 0.01-0.97; P=.047). CONCLUSIONS: The integrated IoT smart patient care system might prevent falls by assisting health care staff with efficient and resilient responses to bed-exit detection. Future product development and research are recommended to introduce IoT into patient care systems combining bed-exit alerts to prevent inpatient falls and address challenges in patient safety.

Expression profiles of tRNA-derived small RNA and their potential roles in oral submucous fibrosis.

BACKGROUND: Although transfer RNA (tRNA) has been found to be the main source of a rich class of noncoding RNA, the tRNA-derived small RNA (tsRNA) has been proved to play an irreplaceable role in the human body, and its dynamic imbalance could affect the progress of the disease. However, the research on tsRNA in oral submucous fibrosis (OSF) is still scarce. METHODS: We sequenced the OSF and validated it by PCR. We found that there were significant differences in their expression levels in OSF. Furthermore, bioinformatic analysis was performed to explore the roles of these fragments in oral submucous fibrosis. RESULTS: Of 126 tsRNAs in OSF were dysregulated, including 73 upregulated tsRNAs and 53 downregulated tsRNAs. The downregulated tiRNA-Val-CAC-002, tRF-Asn-GTT-005, tRF-Trp-CCA-007 and upregulated tRF-Gly-TCC-016, tRF-Pro-TGG-009 showed significant differences by qRT-PCR validation, which were consistent with the results of RNA sequencing. Gene ontology and pathway analysis revealed that tRF-Gly-TCC-016 would possibly promote the formation and progress of OSF through cytokine-cytokine receptor interaction and cAMP signal pathway, while tiRNA-Val-CAC-002 could be primarily concerned with the transition from OSF to oral squamous cell carcinoma (OSCC). CONCLUSION: tRNA-derived fragments are dysregulated and could be involved in the pathogenesis of oral submucous fibrosis. tRF-Gly-TCC-016 and tiRNA-Val-CAC-002 may be new regulatory molecules that could affect the process of OSF by regulating signal pathways through interacting with multiple genes.

Oral submucous fibrosis transforming into squamous cell carcinoma: a prospective study over 31 years in mainland China.

OBJECTIVE: Oral submucous fibrosis (OSF) is an oral mucous disease caused by betel quid chewing. It is controversial whether OSF can transform into oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: In this prospective study, a group of 567 patients with OSF were enrolled from 1986 to 2017 and followed-up until 2019. The cancerous information was collected and analyzed. RESULTS: OSF transformed into OSCC in 32 cases (32/567, 5.6%). The patient's age ranged from 20 to 69 years, and the average age was 52 years. The time taken for transformation ranged from 2 to 24 years, the average being 8.6 years. The cancerous transformation occurred in 18 patients (56%) from years 2 to 9, in 13 patients (41%) from years 10-19 and in 1 patient (3%) from 24 years. We analyzed the betel quid chewing habits and found all 32 patients with OSCC-chewed betel quid. Betel quid chewing was most prevalent in patients aged 40-69 years. Sixteen patients had chewed betel quid for 10-19 years (16/32, 50%) and 19 patients (60%) chewed 10-19 slices each day. The OSCC was located in the left or right buccal regions in 23 patients (23/32; 72%) and in the left or right lingual regions in 4 patients (4/32; 12%). Well, moderately and poorly differentiated squamous cell carcinoma was present in 23 patients (23/32; 72%), 4 patients (3/32; 9%), and 5 patients (5/32; 16%), respectively. CONCLUSION: Our findings supported that OSF is a real oral premalignant disorder. CLINICAL RELEVANCE: The long duration of the transformation from the OSF to OSCC suggests more frequent examinations and corresponding treatments are necessary for OSF patients.

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OBJECTIVES: The mouth restriction of patients with oral submucous fibrosis (OSF) seriously affects their eating food and the quality of life. There are few reports about improving the oral opening degree in patients with OSF. This study aims to explore the effect of oral opening training on the improvement of mouth opening limitation in patients with OSF treated with local injection. METHODS: A total of 220 outpatients with limited mouth opening of OSF were collected from the Center of Stomatology, Xiangya Hospital, Central South University, and randomly divided into a control group and an experiment group (n=110). The control group were treated with local injection of Salvia miltiorrhiza and triamcinolone acetonide, once a week, and 8 times a course. The experimental group were treated with local injection combined with mouth opening training for 2 years. The degree of mouth opening was compared between the 2 groups at the end of local injection treatment, 1 year and 2 years after the treatment. The curative effect was evaluated according to the size of the opening, the lamellar structure of the mucosa, and the condition of the cords. RESULTS: A total of 197 patients completed the whole course of treatment, with 107 in the experimental group and 90 in the control group. At the end of treatment, 1 year and 2 years after the treatment, the degree of mouth opening in the experimental group was (36.14±2.62), (39.67±2.67), and (39.80±2.57) mm, respectively, which was significantly higher than that in the control group (24.71±1.97), (22.82±2.13), and (22.02±2.09) mm, respectively. The difference was significant (P<0.05). The increase of mouth opening in the experimental group was significantly better than that in the control group. Two years after local injection treatment, the effective rate of the experimental group was 97.1%, which was significantly higher than that of the control group (47.8%, P<0.05). CONCLUSIONS: Mouth opening training can significantly increase the degree of mouth opening in patients with OSF treated with local injection.

The push out bond strength of polydimethylsiloxane endodontic sealers to dentin.

BACKGROUND: The purpose of this experiment was to assess the push out bond strength of Polydimethylsiloxane sealers (GuttaFlow 2 and GuttaFlow Bioseal by Colte'ne/Whaledent, Altstätten, Switzerland). AH Plus (Dentsply, DeTrey, Konstanz, Germany) was used as a reference material for comparison. METHODS: Thirty root slices were prepared from the middle third of 10 mandibular premolars. Each slice was 1 ± 0.1 mm thick. Three holes, 0.8 mm wide each, were drilled on the axial side of each root slice. These holes were subjected to standardized irrigations and then dried using paper points. Finally, for each root slice, each hole was filled with exactly one of the following three root canal sealers: AH Plus, GuttaFlow 2 and GuttaFlow Bioseal. After all the holes were filled in that way, the root slices were stored on top of phosphate-buffered saline solution (pH 7.2) soaked gauze for 7 days at the temperature of 37 degrees Celsius. Then, for each root canal sealer on a root slice, the universal testing machine was used to measure the push out bond strength. The differences in push out bond strengths between the three sealer samples were assessed using the Friedman test, while the paired comparisons were assessed using Wilcoxon signed rank test with Bonferroni correction. All statistical tests were two-tailed and the significance level was set at the 5%. RESULTS: According to the Friedman test the distributions of push out bond strengths of AH Plus, GuttaFlow 2 and GuttaFlow Bioseal were different (P < 0.05). Paired comparisons indicated that AH Plus had a significantly superior push out bond strength than GuttaFlow 2 and GuttaFlow Bioseal, while the push out bond strength of GuttaFlow Bioseal was significantly stronger than that of GuttaFlow 2 (P < 0.01). CONCLUSIONS: Based on these findings, AH Plus is a better root canal sealer than GuttaFlow 2 and GuttaFlow Bioseal.

Maternal dietary patterns and gestational diabetes mellitus: a large prospective cohort study in China.

Few studies have explored the relationship between dietary patterns and the risk of gestational diabetes mellitus (GDM). Evidence from non-Western areas is particularly lacking. In the present study, we aimed to examine the associations between dietary patterns and the risk of GDM in a Chinese population. A total of 3063 pregnant Chinese women from an ongoing prospective cohort study were included. Data on dietary intake were collected using a FFQ at 24-27 weeks of gestation. GDM was diagnosed using a 75 g, 2 h oral glucose tolerance test. Dietary patterns were determined by principal components factor analysis. A log-binomial regression model was used to examine the associations between dietary pattern and the risk of GDM. The analysis identified four dietary patterns: vegetable pattern; protein-rich pattern; prudent pattern; sweets and seafood pattern. Multivariate analysis showed that the highest tertile of the vegetable pattern was associated with a decreased risk of GDM (relative risk (RR) 0·79, 95% CI 0·64, 0·97), compared with the lowest tertile, whereas the highest tertile of the sweets and seafood pattern was associated with an increased risk of GDM (RR 1·23, 95% CI 1·02, 1·49). No significant association was found for either the protein-rich or the prudent pattern. The protective effect of a high vegetable pattern score was more evident among women who had a family history of diabetes (P for interaction=0·022). These findings suggest that the vegetable pattern was associated with a decreased risk of GDM, while the sweets and seafood pattern was associated with an increased risk of GDM. These findings may be useful in dietary counselling during pregnancy.

Attachment Style Modifies the Effect of Spousal Support on Postpartum Depression in Women.

Objective: This study aims to examine the impact of spousal support on postpartum depression in women with different attachment styles and assessing if attachment style influences this effect. Methods: From March to May 2022, 96 couples with late-stage pregnant women were randomly selected from tertiary maternity hospitals in Shandong and Guangdong provinces for a prepartum survey. Psychological assessments were conducted using the Adult Attachment Scale, Dyadic Coping Inventory, and the Patient Health Questionnaire-9 (PHQ-9) Depression Scale. To examine the relationship between each variable and postpartum depression, univariate and multiple logistic regression analyses were employed. Additionally, interaction analysis was used to analyze the interplay between different attachment styles and how spousal support influences women's postpartum depression. Results: The findings revealed that even after accounting for confounding variables, prepartum spousal support was an independent predictor of postpartum depression (adjusted odds ratio (OR) = 0.82, 95% CI: 0.69-0.96, P = .015). Women with a secure attachment style showed a significantly lower incidence of postpartum depression compared to those with insecure attachment styles (24.2% vs. 46%, P = .037). In the secure attachment group, spousal support had a protective effect against postpartum depression (adjusted OR = 0.57, 95% CI: 0.36-0.91, P = .018), and attachment style emerged as a potential interactive factor influencing the impact of spousal support on postpartum depression (P for interaction = .029). Conclusion: The provision of spousal support, especially to individuals with secure attachment styles, plays a preventive role in postpartum depression. This underscores the importance of considering attachment styles in interventions targeting postpartum depression prevention.

Empirical Evidence That Complexity Limits Horizontal Gene Transfer.

Horizontal gene transfer (HGT) is a major contributor to bacterial genome evolution, generating phenotypic diversity, driving the expansion of protein families, and facilitating the evolution of new phenotypes, new metabolic pathways, and new species. Comparative studies of gene gain in bacteria suggest that the frequency with which individual genes successfully undergo HGT varies considerably and may be associated with the number of protein-protein interactions in which the gene participates, that is, its connectivity. Two nonexclusive hypotheses have emerged to explain why transferability should decrease with connectivity: the complexity hypothesis (Jain R, Rivera MC, Lake JA. 1999. Horizontal gene transfer among genomes: the complexity hypothesis. Proc Natl Acad Sci U S A. 96:3801-3806.) and the balance hypothesis (Papp B, Pál C, Hurst LD. 2003. Dosage sensitivity and the evolution of gene families in yeast. Nature 424:194-197.). These hypotheses predict that the functional costs of HGT arise from a failure of divergent homologs to make normal protein-protein interactions or from gene misexpression, respectively. Here we describe genome-wide assessments of these hypotheses in which we used 74 existing prokaryotic whole genome shotgun libraries to estimate rates of horizontal transfer of genes from taxonomically diverse prokaryotic donors into Escherichia coli. We show that 1) transferability declines as connectivity increases, 2) transferability declines as the divergence between donor and recipient orthologs increases, and that 3) the magnitude of this negative effect of divergence on transferability increases with connectivity. These effects are particularly robust among the translational proteins, which span the widest range of connectivities. Whereas the complexity hypothesis explains all three of these observations, the balance hypothesis explains only the first one.

Difficult and complicated oral ulceration: an expert consensus guideline for diagnosis.

The complexity of oral ulcerations poses considerable diagnostic and therapeutic challenges to oral specialists. The expert consensus was conducted to summarize the diagnostic work-up for difficult and complicated oral ulcers, based on factors such as detailed clinical medical history inquiry, histopathological examination, and ulceration-related systemic diseases screening. Not only it can provide a standardized procedure of oral ulceration, but also it can improve the diagnostic efficiency, in order to avoid misdiagnosis and missed diagnosis.

[Relationship between the chronic periodontitis and the depression anxiety psychological factor].

OBJECTIVE: To explore the relationship between the chronic periodontitis (CP) and the depression-anxiety psychological factors. METHODS: Thirty-one patients and 29 age, gender-matched volunteers were enrolled for this study. In order to assess the depression-anxiety psychological index, the subjects filled the questionnaire regarding the demographic and socioeconomic information, the oral hygiene habit, the Center for Epidemiologic Studies Depression Scale (CES-D) and the Self Rating Anxiety Scale(ASA). Calculus index (CI), bleeding on probing (BOP), probing depth (PD), clinical attachment loss (CAL), furcation involvement (FI) and tooth mobility were assessed at 6 sites per tooth of all erupted teeth by a manual periodontal probe. The data were analyzed by the analysis of variance, χ(2) test, and multivariable logistic step wise analysis via the software of SPSS 15.0. RESULTS: The mean CAL of the control group was 0.46 ± 0.16,the mean CAL of the moderate, high, and severe CP group was 2.84 ± 0.12, 3.51 ± 0.34, and 4.71 ± 0.51, respectively, which is significant difference between each other (P<0.01). The depression index of the volunteers, the moderate CP, the high CP, and the severe CP was 30.52 ± 3.73, 35.83 ± 7.76, 37.25 ± 6.16, 37.82 ± 5.94, respectively. The anxiety index among the 4 groups was 26.69 ± 3.55, 37.67 ± 6.31, 32.87 ± 5.54, and 35.94 ± 6.30, respectively. The depression and anxiety indexes of the periodontitis groups were higher than those of the control (P<0.01) while there was no significant difference among the 3 CP groups (P>0.05). The multivariate logistic analysis of the relationship between CP and the depression-anxiety psychological factors showed that the depression psychological factor was B=2.301,OR=9.988 while the optimistic coping style was B=-5.174,OR=0.006 in the equation of the regression. CONCLUSION: The depression psychological factor was related to the progression of CP. In addition, the optimistic coping style could prevent the progression of the CP.

Effect of Postoperative Radiotherapy in Thymoma Patients: A SEER-Based Study.

INTRODUCTION: The role of postoperative radiation therapy (PORT) for thymoma is under debate, especially in patients aged ≥60 years with an advanced stage (Masaoka stages III and IV). We aimed to evaluate the efficacy of PORT for thymoma in a population-based registry. METHODS: A retrospective analysis of the Surveillance, Epidemiology, and End Results (SEER) database was conducted to compare the outcomes of thymoma patients with or without PORT. The primary outcomes were overall survival (OS) and cancer-specific survival (CSS). Conditional inference tree analyses were performed for risk classification according to the study variables. Cox regression was performed to evaluate the prognostic effect of PORT in the specific subgroups. RESULTS: A total of 2,236 patients were included. The conditional inference tree analysis identified that an age ≥60, a Masaoka stage ≥3, and the year of diagnosis were important factors when classifying patients into prognostic subgroups. PORT was found to be a protective predictor of OS in patients aged ≥60 years, those with a Masaoka stage III-IV, and those diagnosed after 2005. Further subgroup analyses revealed that PORT was significantly associated with a better OS (HR = 0.77) in patients aged ≥60 years, whereas it was not significantly associated with CSS. CONCLUSIONS: An older age (≥60 years) is critical for predicting survival outcomes in thymoma patients. Moreover, patients aged ≥60 years could benefit from PORT in terms of OS.

tRNA-derived small RNAs: novel regulators of cancer hallmarks and targets of clinical application.

tRNAs are a group of conventional noncoding RNAs (ncRNAs) with critical roles in the biological synthesis of proteins. Recently, tRNA-derived small RNAs (tsRNAs) were found to have important biological functions in the development of human diseases including carcinomas, rather than just being considered pure degradation material. tsRNAs not only are abnormally expressed in the cancer tissues and serum of cancer patients, but also have been suggested to regulate various vital cancer hallmarks. On the other hand, the application of tsRNAs as biomarkers and therapeutic targets is promising. In this review, we focused on the basic characteristics of tsRNAs, and their biological functions known thus far, and explored the regulatory roles of tsRNAs in cancer hallmarks including proliferation, apoptosis, metastasis, tumor microenvironment, drug resistance, cancer stem cell phenotype, and cancer cell metabolism. In addition, we also discussed the research progress on the application of tsRNAs as tumor biomarkers and therapeutic targets.

Fine particulate matter (PM2.5) promotes IgE-mediated mast cell activation through ROS/Gadd45b/JNK axis.

BACKGROUND: Mast cells play an important role in allergic responses and persistently exposure to environmental fine particulate matter (PM2.5) exacerbates allergic diseases,but the details remained elucidative. OBJECTIVES: To investigate the effect of PM2.5 on IgE-mediated mast cell responses through an IgE-mediated mouse model and mast cell activation. METHODS: The ß-hexosaminidase release and a BALB/c model of passive cutaneous anaphylaxis (PCA) was used to test IgE-mediated mast cells activation in vitro and in vivo. RNA-Seq technique was conducted to study the gene expression profile. Reactive oxygen species (ROS) production was measured by flow-cytometry. RT-PCR,WB and ELISA were performed to examine targeting molecules expression. RESULTS: PM2.5 facilitated IgE-mediated degranulation and increased cytokines expression in mast cells. Meanwhile, the Evan's blue extravasation as well as serum cytokines in mice was increased after treatment with PM2.5. Furthermore, PM2.5 treatment dramatically increased the expression of Gadd45b which is an oxidative stress molecule that directly activates down-stream pathway, such as MEKK4/JNK. PM2.5 treatment activated MEKK4, JNK1/2 but not ERK1/2 and p38. Meanwhile, Knockdown of Gadd45b significantly attenuated PM2.5-mediated JNK1/2 activation and expression of cytokines. In addition, a JNK1/2-specific inhibitor SP600125 blocked IgE-mediated mast cell activation and cytokine release in PCA model mice. Moreover, PM2.5 treatment increased the ROS level and ROS inhibitor dramatically blocked the PM2.5-induced ROS production and reversed the PM2.5-mediated gene expression in the mitochondrial respiratory chain. CONCLUSIONS: PM2.5 regulates ROS production through Gadd45b/MEKK4/JNK pathway, facilitating IgE-mediated mast cell activation.

XBP1- IGFBP3 Signaling Pathway Promotes NSCLC Invasion and Metastasis.

Lung cancer is the most frequently diagnosed cancer and the main cause of cancer death in the world. X-box binding protein 1 (XBP1), which is an important transcription factor involved in regulating the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress, might act as a potent oncogenic protein in the processes of tumorigenesis, tumor proliferation and metastasis in various cancers. However, the clinical significance and pathological role of XBP1 in non-small cell lung cancer (NSCLC) remains unknown. In this study, we investigated the expression of XBP1s protein in the 104 NSCLC tumor tissues and matched adjacent normal lung tissues (ANLT) by Immunohistochemical (IHC), and we found overexpressed XBP1s protein was associated with NSCLC TNM stages, lymph node metastasis and poor prognosis. The further gain-and loss-of-function experiments indicated overexpression of XBP1s protein promoted cell invasion, migration and metastasis both in vitro and in vivo. Further study showed XBP1s protein could upregulate insulin-like growth factor binding protein-3 (IGFBP3) expression, and regulated NSCLC cells invasion and metastasis by regulating IGFBP3. Taken together, XBP1s protein is markedly overexpressed in NSCLC and serves as an oncogene that play a critical role in NSCLC tumorigenesis and development. Importantly, XBP1s protein might not only be a potential biomarker for metastasis and prognosis but also a potential therapeutic target in NSCLC.

[Therapeutic effect of the combination of traditional Chinese medicine and western medicine on patients with oral submucous fibrosis].

OBJECTIVE: To observe the therapeutic effect of salvia miltiorrhiza and prednisolone on patients with oral submucous fibrosis (OSF). METHODS: A total of 60 medium-term OSF patients and 60 advanced stage OSF patients were randomly divided into the first group (treated with both salvia miltiorrhiza and prednisolone) and the second group (treated with prednisolone alone). The clinical effect was compared between each group after 3-month treatment. RESULTS: Difference was found in the lesion area of the medium-term cases and the advanced stage cases of the first group before the treatment [(10.37+/-3.40) cm2, (19.60+/-3.27) cm2] and after the treatment [(5.90+/-4.10) cm2, (16.33+/-4.02) cm2] (P<0.05). Significant difference was found in the mouth opening before the treatment [(3.41+/-0.77) cm, (1.98+/-0.39) cm] and after the treatment [(3.87+/-0.67) cm, (2.26+/-0.46) cm] (P<0.05) in the first group. There was significant difference in the lesion area and mouth opening of the medium-term cases of the second group before the treatment [(10.87+/-3.18) cm2, (3.57+/-0.75) cm] and after the treatment [(6.70+/-3.75) cm2, (3.97+/-0.69) cm] (P<0.05). No difference in the lesion area and mouth opening of the advanced stage cases of the second group was found (P>0.05). There was difference in the therapeutic efficacy between the first group (70%) and the second group (16.67%) of the advanced stage cases (P<0.05), but not in the clinical effect between the 2 groups of the medium-term cases (P>0.05). The side effect of prednisolone could be reduced while used together with salvia miltiorrhiza. CONCLUSION: There is obvious advantage in treating OSF by the combination of salvia miltiorrhiza and prednisolone.

Complete remission in a patient with advanced renal pelvis carcinoma with lung metastasis treated with durvalumab immunotherapy: a case report.

For early-stage upper urothelial carcinoma, total nephroureterectomy combined with bladder sleeve resection is the standard treatment. However, for patients with advanced disease, there is a lack of effective therapeutic strategies. In recent years, with an increased understanding of cancer immunobiology, systemic immunotherapies targeting immune checkpoint inhibition has been explored and clinically used in the area of urothelial carcinoma. The programmed cell death 1 receptor (PD-1) and its ligand (PD-L1) are important negative regulators of immune activity, preventing the destruction of normal tissues and autoimmunity. Nowadays, five immune checkpoint inhibitors blocking PD-1 (pembrolizumab, nivolumab) or PD-L1 (atezolizumab, durvalumab, and avelumab) have been approved by the United States Food and Drug Administration (US FDA) for the first- or second-line use in urothelial carcinoma, based on durable response and manageable safety profiles observed in relevant clinical trials. In this study, we present the case of a 64-year-old patient with renal pelvis carcinoma who went on to develop lung metastasis after postoperative chemotherapy. CT scan showed multiple scattered solid small nodule foci in both lungs (considered as metastasis). The patient received immunotherapy with PD-L1 monoclonal antibody (Durvalumab) alone, and achieved complete remission (CR) after 3 cycles of treatment. During the treatment, slight weakness was reported, and no nausea, fever and other adverse events were observed. This case shows that durvalumab could effectively and safely treat a case of renal pelvis carcinoma with lung metastases.