Feedback loop between hepatocyte nuclear factor 1α and endoplasmic reticulum stress mitigates liver injury by downregulating hepatocyte apoptosis.

Hepatocyte nuclear factor alpha (HNF1α), endoplasmic reticulum (ER) stress, and hepatocyte apoptosis contribute to severe acute exacerbation (SAE) of liver injury. Here, we explore HNF1α-ER stress-hepatocyte apoptosis interaction in liver injury. LO2, HepG2 and SK-Hep1 cells were treated with thapsigargin (TG) or tunicamycin (TM) to induce ER stress. Carbon tetrachloride (CCl4) was used to induce acute liver injury in mice. Low-dose lipopolysaccharide (LPS) exacerbated liver injury in CCl4-induced mice. Significant apoptosis, HNF1α upregulation, and nuclear factor kappa B (NF-κB) activation were observed in human-derived hepatocytes during ER stress. Knockdown of Rela, NF-κB p65, inhibited the HNF1α upregulation. Following CCl4 treatment ER stress, apoptosis, HNF1α expression and RelA phosphorylation were significantly increased in mice. HNF1α knockdown reduced activating transcription factor 4 (ATF4) expression, and aggravated ER stress as well as hepatocyte apoptosis in vivo and in vitro. The double fluorescent reporter gene assay confirmed that HNF1α regulated the transcription of ATF4 promoter. LPS aggravated CCl4-induced liver injury and reduced HNF1α, and ATF4 expression. Therefore, in combination, HNF1α and ER stress could be mutually regulated forming a feedback loop, which helps in protecting the injured liver by down-regulating hepatocyte apoptosis. Low-dose LPS aggravates hepatocyte apoptosis and promotes the SAE of liver injury by interfering with the feedback regulation of HNF1α and ER stress in acute liver injury.

Guidewire-Assisted Reduction Technology Combined with Postural Reduction Improves the Success Rate of Internal Vein Catheterisation.

Objective: To investigate the value of guidewire-assisted reduction technology (which increases the stiffness of a catheter through the use of a guidewire, thereby protecting the puncture point and distal vein from breakage) combined with postural reduction for malpositioned catheters in the internal jugular vein during peripherally inserted central venous catheter catheterisation. Methods: From January 2015 to August 2020, we used ultrasound to perform guided puncture and monitoring. We identified the tip of the catheter as malpositioned in the internal jugular vein in 99 patients during the catheterisation process. These patients were divided randomly into a control group and an experimental group. In the control group, 43 cases received guidewire-assisted reduction technology, while in the experimental group, 56 patients received guidewire-assisted reduction technology combined with an upright posture. This study compared the efficacy of these two methods. Results: The results showed that 30 catheters were reduced successfully in the control group, with a success rate of 69.8%. In the experimental group, 53 cases were successfully reduced, with a success rate of 94.6%. The catheter reduction success rate in the experimental group was significantly higher than in the control group; this was a statistically significant difference (P=0.001). Conclusion: Guidewire-assisted reduction technology combined with postural reduction can improve the success rate of the reduction of malpositioned catheters in the internal jugular vein.

Acidogenic phosphorus recovery from the wastewater sludge of the membrane bioreactor systems with different iron-dosing modes.

A novel acidogenic phosphorus recovery (APR) process was developed in combination with Fe(III)-based chemical phosphorus removal and a membrane bioreactor (MBR) for enhanced wastewater treatment and effective P recovery. Two different system configurations were evaluated: Fe-dosing MBR (Fe-MBR), with the Fe-dosing into the MBR, and Fe-enhanced primary sedimentation followed by the MBR (FeP-MBR). The results show that both systems performed well for enhanced nutrient (N and P) removals and P recovery, with approximately 50% of the total P recovered from the municipal wastewater in the form of vivianite. Compared to the Fe-MBR system, FeP-MBR achieved more efficient P recovery under low food-waste loading conditions, maintained a higher ratio of biomass in activated sludge and experienced a slower rate of membrane fouling. Important functional bacteria were identified, including Prevotella and Selenomonas, which are active in hydrolysis and acidogenesis of sludge, and Aeromonas and Sulfurospirillum, which are involved in dissimilatory iron reduction.

Eugenol alleviated breast precancerous lesions through HER2/PI3K-AKT pathway-induced cell apoptosis and S-phase arrest.

Eugenol can be separated from the oil extract of clove bud, and has many pharmacological functions such as anticancer and transdermal absorption. HER2/PI3K-AKT is a key signaling pathway in the development of breast cancer. In this study, 80 µM eugenol could significantly inhibit the proliferation of HER-2 positive MCF-10AT cells and the inhibition rate was up to 32.8%, but had no obvious inhibitory effect on MCF-7 and MCF-10A cells with HER2 weak expression. Eugenol also significantly induced human breast precancerous lesion MCF-10AT cell apoptosis and cell cycle S-phase arrest, but the biological effects nearly disappeared after HER2 over-expression through transfecting pcDNA3.1-HER2. In MCF-10AT cells treated by 180 µM eugenol, the protein expressions of HER2, AKT, PDK1, p85, Bcl2, NF-κB, Bad and Cyclin D1 were decreased and the decreased rates were respectively 63.0%, 60.0%, 52.9%, 62.9%, 37.1%, 47.2%, 61.7%, 59.1%, while the p21, p27 and Bax expression were increased by 4.48-, 4.76- and 2.57-fold respectively. In the rat models of breast precancerous lesion, 1 mg eugenol for external use significantly inhibited the progress of breast precancerous lesion and the occurrence rate of breast precancerous lesions and invasive carcinomas was decreased by about 30.5%. Furthermore eugenol for external (1 mg) markedly decreased the protein expressions of HER2 (62.9%), AKT (58.6%), PDK1 (56.4%), p85 (54.3%), Bcl2 (59.3%), NF-κB (65.7%), Bad (64.0%), Cyclin D1 (43.0%), while p21, p27 and Bax protein expressions were respectively increased 1.83-, 2.52- and 2.51-fold. The results showed eugenol could significantly inhibit the development of breast precancerous lesions by blocking HER2/PI3K-AKT signaling network. So eugenol may be a promising external drug for breast precancerous lesions.

[Study on the concordance of objective multi-parameters analysis and perceptual evaluation].

OBJECTIVE: Through exploring the concordance of objective multi-parameters analysis and perceptual evaluation, to establish an objective multi-parameters evaluation protocol of voice disorder and to make the evaluation of voice objectification and quantification. METHODS: Voice samples from 271 patients (124 female and 147 male)with dysphonia and 69 control subjects with normal voice (37 female and 32 male)were recorded and assessed by a jury composed of 5 experts in phoniatrics from different hospitals. The jury was instructed to classify voice samples according to the G (grade) component of the GRBAS scale on a visual analogue scale secondarily transformed in a 4-point scale ranging from 0 for normal to 3 for severe dysphonia. The voice samples were unified sentences and ordered randomly 3 times, the mean of 3 evaluation scores were the final results. The objective parameters, including fundamental frequency (F0), jitter, shimmer, fundamental frequency standard deviation (F0SD), normalized noise energy (NNE), harmonic-to-noise ratio (HNR) and maximal phonatory time (MPT), were measured on a 2-second sustained vowel/a/including its initial segment, using the software Dr. Speech for Windows. The data were analyzed using SPSS11.0. RESULTS: All objective parameters except for F0 had high correlation with G and the variance tendency of these parameters values was coherent with the extent of voice disorder. And there were statistical differences between adjacent voice disorder groups. Male and female objective multi-parameters protocols were established respectively consisting of jitter, shimmer, F0SD, NNE, HNR and MPT using discriminant analysis (P < 0.05). The concordance between perceptual evaluation and objective multi-parameters evaluation was 81.6% in male and 83.2% in female. The concordance of evaluation of normal voice and severe voice disorder groups were better than that of mild and moderate voice disorder groups. All mis-grading voices were judged in the adjacent voice group. CONCLUSIONS: The objective parameters of voice are able to reflect the characteristic of its perceptual evaluation and the concordance between perceptual evaluation and objective multi-parameters evaluation is good. The objective multi-parameters evaluation protocol we established could provide an objective and quantitative evaluation method for voice disorders.

[Effect of acupuncture and massage at tendon on F-wave of electromyogram in the patient of flexor spasm of the upper limb after operation of cervical spondylosis].

OBJECTIVE: To explore the mechanism of acupuncture and massage at the tendon in treatment of the upper limb flexor spasm after cervical operation. METHODS: Fifty-six cases were randomly divided into a treatment group (n = 30) treated with acupuncture and massage at the tendons, and a control group treated with traditional acupuncture and medication. Changes of F-wave, time limit and threshold value in electromyogram before and after treatment were investigated in the both groups. RESULTS: Before treatment, the F-wave in the patient of the upper limb spasm post-cervical operation was characterized by high amplitude, long time limit and low threshold value, with no significant difference between the two groups (P > 0.05); after treatment, the amplitude lowered (P < 0.01), the time limit shortened (P < 0.001) in the treatment group and no significant changes were found in the control group (P > 0.05), but the amplitude of F-wave in the treatment group was significantly lower than that in the control group (P < 0.05). The threshold value significantly increased in the two groups, with the treatment group more significantly increased than the control group (P < 0.05). CONCLUSION: Acupuncture and massage at tendons can relieve the spasm through lowing the excitement in the cells of the anterior horn of the spinal cord, decreasing the amplitude and time limit of the F-wave, increasing the threshold value and reducing traction reflection.