Comparison of Efficacy and Safety of Different Doses of Dexmedetomidine for Epidural Labor Analgesia.

Objective: To explore the efficacy and safety of different doses of dexmedetomidine (DEX) for epidural labor analgesia (ELA). Methods: From June 2021 to June 2022, 147 parturients who underwent ELA in our hospital were selected and divided into low- (0.5 µg/kg DEX), medium- (0.75 µg/kg DEX), and high-dose (1.0 µg/kg DEX) groups (n = 49 for each) according to the random number table method. The analgesic effect was assessed using the Ramsay sedation score and Visual Analogue Scale (VAS), and the labor duration, mean arterial pressure (MAP), and heart rate (HR) before and after analgesia, vaginal bleeding within 2 h postpartum, and delivery outcomes (the cesarean section conversion rate and the neonatal Apgar score) were statistically analyzed. Furthermore, the incidence of adverse reactions was calculated, and maternal satisfaction with delivery was investigated. Results: After analgesia, the the Ramsay and labor duration were higher in the high-dose group than those in the low- and medium-dose groups, and the VAS scores was lowerin the high-dose group than those in the low- and medium-dose groups(P < 0.05), while no difference was identified among the three groups in terms of the cesarean section conversion rate and the neonatal Apgar score (P > 0.05). The high-dose group had the greatest fluctuations in MAP and HR levels before and after analgesia than the other two groups, with a higher incidence of adverse reactions (P < 0.05). Finally, the survey of delivery satisfaction showed no significant difference in delivery satisfaction among the three groups (P > 0.05). Conclusion: DEX has excellent performance in ELA, which can effectively relieve the pain of puerperae and shorten the labor process. Among them, low-dose DEX has higher safety and is recommended as the first choice. Trial Registrations. This trial is registered with ML2021073.

Gene therapy targeting inflammatory pericytes corrects angiopathy during diabetic wound healing.

Wound healing is impaired in the diabetic status, largely attributable to diabetes-associated angiopathy. Pericytes play critical roles in the stabilization of the formed vessels. The loss and dysfunction of pericytes have been reported in inflammation during diabetes and associated with the pathology of diabetic angiopathy. However, a practical approach that targets inflammatory pericytes to improve diabetic wound healing is lacking. In the current study, we showed that the inflammatory pericytes from wound skin of diabetic patients were impaired in growth potential and underwent oxidative stress and apoptosis. Expression of antioxidant gene oxidation resistance protein 1 (OXR1) specifically in pericytes through an adenovirus carrying OXR1 under a pericyte-specific neuron glia antigen-2 (NG2) promoter (AV-NG2p-OXR1) relieved the oxidative stress, reduced the apoptosis, and recovered the growth potential in diabetic pericytes. Moreover, expression of OXR1 in diabetic pericytes retrieved their potential of both suppressing the migration of co-cultured HUVECs and inducing cell aggregates at the branching points, indicating a functional recovery. In vivo gene therapy using this AV-NG2p-OXR1 to DB/DB mice, the mouse model for type 2 diabetes, significantly improved wound healing, likely through enhancing blood flow at the wound rather than increasing vessel density. Together, our data suggest that gene therapy targeting inflammatory pericytes may improve diabetes-associated impaired wound healing.

Immortalization up-regulated protein promotes tumorigenesis and inhibits apoptosis of papillary thyroid cancer.

The incidence of thyroid cancer is increasing in recent years worldwide, but the underlying mechanisms await further exploration. We utilized the bioinformatic analysis to discover that Immortalization up-regulated protein (IMUP) could be a potential oncogene in the papillary thyroid cancer (PTC). We verified this finding in several databases and locally validated cohorts. Clinicopathological features analyses showed that high expression of IMUP is positively related to malignant clinicopathological features in PTC. Braf-like PTC patients with higher IMUP expression had shorter disease-free survival. The biological function of IMUP in PTC cell lines (KTC-1 and TPC-1) was investigated using small interfering RNA. Our results showed that silencing IMUP suppresses proliferation, migration and invasion while inducing apoptosis in PTC cell lines. Changes of the expression of apoptosis-related molecules were identified by real-time quantitative polymerase chain reaction and Western blotting. We also found that YAP1 and TAZ, the critical effectors in the Hippo pathway, were down-regulated when the IMUP is silenced. Rescue experiments showed that overexpression of YAP1 reverses the tumour inhibitory effect caused by IMUP knockdown. Our study demonstrated that IMUP has an oncogenic function in PTC and might be a new target gene in the treatment of PTC.

Proto-oncogene RTL4 promotes tumorigenesis and invasiveness of papillary thyroid cancer.

BACKGROUND: Although the prognosis of papillary thyroid carcinoma (PTC) is good, its widespread prevalence still degrades the quality of life of tens of thousands of patients. PTC can even be life-threatening as a result of its aggressiveness and metastasis. METHODS: Using complete transcriptome sequence analysis, cutting-edge research has revealed many tumor-associated genes. These related genes help us better understand the tumorigenesis and progression of PTC. We discovered that retrotransposon Gag like 4 (RTL4) is a novel potential PTC-associated gene. By Quantitative real-time polymerase chain reaction (qRT-PCR), we observed an obvious upregulation of RTL4 in PTC tissue. And, we validated the expression characteristics of RTL4 using data from the Cancer Genome Atlas (TCGA). Furthermore, we down-regulated RTL4 expression levels in relevant cell lines and studied the biological function of the RTL4 line in PTC by cell proliferation, colony formation, migration and invasion assays. RESULTS: In the present study, high expression of RTL4 suggested lymph node metastasis (P = 0.028) and was associated with the pathological type (P = 0.001). RTL4 had the validity of distinguishing PTC tissues and normal tissues showed an AUC of 87.53% for the TCGA data set. The downregulation of RTL4 in the PTC cell lines distinctly inhibited cell colony formation, proliferation, migration, and invasion. CONCLUSIONS: The result revealed RTL4 is closely related to the occurrence and development of PTC. RTL4 may participate in the HOTAIR-miR-206-ZCCHC16 ceRNA regulatory network and be regulated and play a role in the ceRNA regulatory network. It may be used as a target or indicator for the treatment and prognosis of PTC.

Downregulating integrin subunit alpha 7 (ITGA7) promotes proliferation, invasion, and migration of papillary thyroid carcinoma cells through regulating epithelial-to-mesenchymal transition.

Thyroid cancer is one of the common malignancies of the endocrine system and the number of thyroid cancer cases is increasing constantly. Significant work has focused on the molecular mechanisms of thyroid cancer, but many mechanisms remain undiscovered. In this study, we employed a comprehensive analysis of whole-transcriptome resequencing derived from paired papillary thyroid cancer (PTC) and normal thyroid tissues. We performed a massive parallel whole-transcriptome resequencing of matched PTC and normal thyroid tissues in 19 patients and found that integrin subunit alpha 7 (ITGA7) was downregulated in thyroid tumor tissues, but the function of ITGA7 in this cancer is still unclear. We also discovered that ITGA7 gene in thyroid cancer tissues was downregulated compared to paired adjacent non-tumor tissues by real-time quantitative polymerase chain reaction. After transfection with small interfering RNA to knock down ITGA7, the abilities of colony formation, proliferation, migration, and invasion were enhanced in PTC cell lines (TPC1 and KTC-1). Meanwhile, ITGA7 knockdown decreased apoptotic cell death in thyroid cells but promoted the expressions of N-cadherin and vimentin and decreased E-cadherin expression by epithelial-to-mesenchymal transition, which may induce invasion and migration. In conclusion, these results indicated that ITGA7 is involved in the progress of PTC and might act as a tumor suppressor gene.

LRRC52-AS1 is associated with clinical progression and regulates cell migration and invasion in papillary thyroid cancer.

The incidence of thyroid cancer has increased in recent decades. The potential molecular mechanisms of papillary thyroid cancer (PTC) are still to be uncovered. In recent years, a number of studies reported that LRRC super family members are up-regulated in cancer cells. Cancer cells can experience a feature change from an epithelial to a mesenchymal phenotype, which is called epithelial-mesenchymal transition (EMT) during cancer progression. We found that LRRC52-AS1 is highly expressed in PTC cell lines rather than normal tissues and this observation was consistent with The Cancer Genome Atlas (TCGA) cohort. In a word, LRRC52-AS1 is associated with clinical progression in papillary thyroid cancer. In vitro experiments showed that knocking down LRRC52-AS1 significantly decreased the migration and invasion of the PTC cell lines (BCPAP and TPC). Meanwhile, LRRC52-AS1 may influence the progress of papillary thyroid cancer via mesenchymal markers N-cadherin, vimentin and TAZ. The LRRC52-AS1 gene is up-regulated in papillary thyroid cancer, and knockdown of LRRC52-AS1 could restrain cellular migration, and invasion in vitro. This study indicated that LRRC52-AS1 is a gene associated with PTC and might become a potential therapeutic target in PTC.

ITGA7 functions as a tumor suppressor and regulates migration and invasion in breast cancer.

BACKGROUND: Breast cancer is the most common malignancy in women and the underlying mechanism of breast cancer cell metastasis is still far from uncover. Integrin subunit alpha 7 (ITGA7) is a functioning protein. It has been detected in many malignancies. But the function of ITGA7 in breast cancer is not clear. Our aim is to explore ITGA7 expression and its role in breast cancer. METHODS: Real-time PCR was performed to determine ITGA7 expression in BC tissues and normal adjacent tissues. The specific functions of ITGA7 in breast cancer cell lines (MDA-MB-231 and BT-549) transfected with small interfering RNA were determined through migration, invasion assays. Western blot assays were performed to determine the expression of c-met and vimentin. RESULTS: ITGA7 was down-regulated in breast cancer tissues compared to the adjacent normal tissues (T:N =7.68±27.38: 41.01± 31.47, P<0.001) and this observation was consistent with the TCGA cohort (T:N =4.51±0.45:5.40±0.61, P<0.0001). In vitro experiments showed that knocking down ITGA7 significantly inhibited the migration and invasion of the breast cancer cell lines (MDA-MB-231 and BT-549). Meanwhile, knockdown of ITGA7 promoted c-met and vimentin expression, which may induce invasion and migration. CONCLUSION: ITGA7 plays an important tumorigenic function and acts as a suppress gene in breast cancer. Our findings indicate that ITGA7 was the gene associated with breast cancer.

Research on the treatment of phosphoric wastewater by ultrasound-assisted microelectrolysis method.

In this research work, ultrasound was introduced to the microelectrolysis (ME) method to improve the treatment efficiency for phosphoric wastewater. The effects of treatment time, Fe/C ratio (v/v) and iron filings dosage on the efficiency of phosphorus removal from wastewater with different initial pH values were investigated. The results showed that the phosphorus removal efficiency by the ME method was significantly enhanced in the presence of ultrasound. The maximum removal rate of phosphorus (RRP) for the wastewater with an initial pH value of 4.0 was 92.4% after 60 min of treatment when the Fe/C and Fe/H2O volume ratio were 2/1 and 1/10, respectively. The reaction kinetics analysis indicated that the phosphorus degradation processes for the ultrasonic and ME methods as well as the ultrasonically assisted ME method (UME) were in accordance with the pseudo-first-order kinetic model. The synergetic effect of the combined ultrasound and ME method for phosphorus removal was also studied by reaction kinetics analysis.