Objective To observe the effects of Yiqi Huoxue Tuodu Prescription on Keap1Nrf2/HO-1 signaling pathway in rats with chronic nonbacterial prostatitis(CNP);To explore its mechanism for the treatment of CNP.Methods CNP rat model was prepared using castration combined with estrogen induction method.Totally 48 SD rats were divided into blank group,model group,celecoxib group and Yiqi Huoxue Tuodu Prescription group according to the random number table method,with 12 rats in each group.In the celecoxib group,celecoxib suspension was instilled 0.035 g/kg,and in the Yiqi Huoxue Tuodu Prescription group,Yiqi Huoxue Tuodu Prescription water decoction was instilled 8.64 g/kg,and the blank group and the model group were instilled with equal volume of normal saline for 28 days.Mechanical pain threshold in rats was measured using Von Frey fiber optic pain gauge,HE staining was used to observe pathological changes in prostate tissue and pathological scoring,the content of reactive oxygen species(ROS)in prostate tissue were detected by chemical fluorescence method and the glutathione peroxidase(GSH-Px)activity and malondialdehyde(MDA)content in prostate tissue were detected by colorimetric method,Western blot was used to detect the expressions of Kelch like ECH related protein 1(Keap1),nuclear factor E2 related factor 2(Nrf2),and heme oxygenase-1(HO-1)protein in prostate tissue.Results Compared with the blank group,rats in the model group had significantly lower mechanical pain threshold and significantly decreased prostate index(P<0.01);the size of the glandular cavity in prostate tissue varied,with the disappearance of secretions in the cavity,interstitial looseness and edema,a large amount of fibrous tissue hyperplasia and inflammatory cell infiltration,and a significant increase in pathological scores(P<0.01);the contents of ROS and MDA in prostate tissue significantly increased,the activity of GSH-Px significantly decreased(P<0.01),the expression of Keap1 and Nrf2 proteins significantly decreased,and the expression of HO-1 protein significantly increased(P<0.01,P<0.05).Compared with the model group,the mechanical pain threshold of the rats in the Yiqi Huoxue Tuodu Prescription group was significantly higher(P<0.01);there was mild damage to prostate tissue,with a small amount of fibrous hyperplasia and inflammatory cell infiltration,and a significant decrease in pathological scores(P<0.01,P<0.05);the contents of ROS and MDA in prostate tissue significantly decreased,and the GSH-Px activity significantly increased(P<0.01),the Keap1 and Nrf2 protein expressions significantly increased and HO-1 protein expression significantly decreased in prostate tissue(P<0.01,P<0.05).Conclusion Yiqi Huoxue Tuodu Prescription can effectively improve the histopathological morphology and increase the pain threshold of the prostate gland in CNP rats,and its mechanism of action may be related to the regulation of Keap1/Nrf2/HO-1 signaling pathway and reduction of oxidative stress damage in prostate tissue of rats.

Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly worldwide and is characterized by degeneration of the photoreceptor, retinal pigment epithelium, Bruch membrane and choriocapillaris complex.Impairment of RPE cell function is an early and critical event in the molecular pathways leading to clinically relevant AMD changes.Programmed cell death (PCD) plays an important role in response to stress and regulation of homeostasis and disease.In recent years, multiple studies have shown that apoptosis, pyroptosis, necroptosis and ferroptosis are likely involved in RPE cell PCD and correlate with the onset and development of AMD.There may be interaction or synergy between the various death pathways.This article reviewed the pathogenic mechanism of apoptosis, pyroptosis, necroptosis and ferroptosis in retinal pigment epithelial cell and their research progress in AMD, which might provide new approaches for the prevention and treatment of AMD.

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia

Objective:To investigate the value of the 8-channel eye surface phased array coil in improving image quality and demonstrating ocular masses on 3.0 T MR scanner.Methods:From July 2018 to January 2020, the data of orbital MRI in 692 patients with ocular masses on 6 medical centers were prospectively collected. The patients were simple randomly assigned into 8-channel eye surface phased array coil group (413 patients) or 8-channel head phased array coil group (279 patients), with the same MRI sequences. The signal to noise ratio (SNR) and contrast to noise ratio (CNR) were calculated in orbital anatomy structures and masses (eyelid mass, intraocular mass, lacrimal mass and orbital mass). The image quality scores including motion artifact, mass margin, the relationship between the mass and adjacent structures, and overall image quality were recorded. The differences of image quality between the two groups were compared by two independent sample t-test or Wilcoxon rank test. Results:The SNR and CNR were higher in eye surface coil group than those in head coil group ( P<0.05). The scores of ocular movement artifacts were higher in head coil group than those in surface coil group ( P<0.05). The scores of intraocular mass margin, the relationship between the mass and adjacent structures, and overall image quality were higher in surface coil group than those in head coil group ( P<0.001). There were no significant differences in mass margin, the relationship between the mass and adjacent structures, and overall image quality scores of eyelid, lacrimal gland, and orbital mass between the two groups ( P>0.05). Conclusion:3.0 T MR scanner combined with the 8-channel eye surface phased array coil can improve the SNR and CNR of orbital MR images, the demonstration of the intraocular mass margin and the relationship between the mass and adjacent structures.

Objective:To investigate the value of periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) in improving ability of demonstrating ocular masses on 3.0 T MR scanner.Methods:This study was a multi-center prospective study involving 6 centers. From July 2018 to January 2020, totally 413 patients with ocular masses from 6 centers were prospectively enrolled, and all of them underwent T 1WI and T 2WI, PROPELLER T 1 FLAIR and T 2WI, and contrast-enhanced scans. The signal intensity of eyelid, vitreous body, lacrimal gland, intraorbital segment of optic nerve, and orbital masses of eyelid, intraocular, lacrimal gland and retrobulbar were measured by two radiologists, and the signal to noise ratio (SNR) and contrast noise ratio (CNR) were calculated. The 5-point scoring method was used to evaluate the motion artefacts, tumor edges and the relationship between the tumor and adjacent structures, and the overall score of image quality was calculated. Paired t-test or Wilcoxon signed rank test was used to compare the image quality between PROPELLER and non-PROPELLER images. Results:The SNR and CNR of PROPELLER T 2WI were higher than those of non-PROPELLER T 2WI (all P<0.001). The SNR and CNR of PROPELLER T 1 FLAIR were lower than those of non-PROPELLER T 1WI (all P<0.05). The scores of artefacts and overall image quality in PROPELLER images were higher than those in non-PROPELLER images (all P<0.001). The tumor edge and the relationship between the tumor and adjacent structures scores of eyelid, intraocular, and lacrimal gland masses in PROPELLER images were higher than those in non-PROPELLER images (all P<0.001),while compared to non-PROPELLER images, retro-global masses in PROPELLER images showed no significant differences (all P>0.05). Conclusion:PROPELLER can reduce ocular motion artefacts, effectively improve image quality and ability of demonstrating anterior (eyelid, intraocular, and lacrimal gland) masses.

Objective:To investigate the changes of quadriceps femoris thickness with the length of stay in intensive care unit (ICU) in patients with sepsis, and to evaluate the diagnostic value of muscle changes in mortality.Methods:A prospective study was conducted, and 92 patients with sepsis who were admitted to the ICU of the Affiliated Hospital of Jining Medical College from January 2020 to December 2021 were enrolled. The thickness of quadriceps femoris [including the quadriceps femoris muscle thickness at the midpoint of the anterior superior iliac spine and the upper edge of the patella (M-QMLT), and at the middle and lower 1/3 of the patella (T-QMLT)] measured by ultrasound 1 day (D1), 3 days (D3), and 7 days (D7) after admission to the ICU were collected. The atrophy rate of quadriceps femoris was calculated 3 and 7 days after admission to the ICU compared with 1 day [(D3-D1)/D1 and (D7-D1)/D1, (TD3-TD1)/TD1 and (TD7-TD1)/TD1, respectively]. The demographic information, underlying diseases, vital signs when admission to the ICU and in-hospital mortality of all patients were recorded, and the differences of the above indicators between the two groupswere compared. Multivariate Logistic regression was used to analyze the influence of quadriceps femoris muscle thickness and atrophy rate on in-hospital mortality of septic patients. The receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of quadriceps femoris muscle thickness and atrophy rate on in-hospital mortality of septic patients.Results:A total of 92 patients with severe sepsis were included, of which 41 patients died in hospital, 51 patients discharged. The in-hospital mortality was 44.6%. The muscle thickness of quadriceps femoris in severe septic patients decreased with the prolongation of ICU stay, and there was no significant difference between the two groups at the first and third day of ICU admission. The muscle thickness of quadriceps femoris at different measuring positions in the survival group was significantly greater than those in the death group 7 days after admission to the ICU [M-QMLT D7 (cm): 0.50±0.26 vs. 0.39±0.19, T-QMLT D7 (cm): 0.58±0.29 vs. 0.45±0.21, both P < 0.05]. The atrophy rate of quadriceps femoris muscle thickness at different measuring positions 3 and 7 days after admission to ICU in the survival group was significantly lower than those in the death group [(D3-D1)/D1: (8.33±3.44)% vs. (9.74±3.91)%, (D7-D1)/D1: (12.21±4.76)% vs. (19.80±6.15)%, (TD3-TD1)/TD1: (7.83±4.26)% vs. (10.51±4.75)%, (TD7-TD1)/TD1: (11.10±5.46)% vs. (20.22±6.05)%, all P < 0.05]. Multivariate Logistic regression analysis showed that M-QMLT D7, T-QMLT D7, (D3-D1)/D1, (D7-D1)/D1, (TD3-TD1)/TD1, (TD7-TD1)/TD1 were independent risk factors for in-hospital mortality (all P < 0.05). The results were stable after adjusting for confounding factors. ROC curve analysis showed that (TD7-TD1)/TD1 [area under the ROC curve (AUC) was 0.853, 95% confidence interval (95% CI) was 0.773-0.934] was superior to (D7-D1)/D1, T-QMLT D7, M-QMLT D7, (TD3-TD1)/TD1 and (D3-D1)/D1 [AUC was 0.821 (0.725-0.917), 0.692 (0.582-0.802), 0.683 (0.573-0.794), 0.680 (0.569-0.791), 0.622 (0.502-0.742)]. Conclusions:For septic patients in ICU, bedside ultrasound monitoring of quadriceps femoris muscle thickness and atrophy rate has a certain predictive value for in-hospital mortality, and a certain guiding significance in clinical treatment and predicting the prognosis of sepsis.

Objective:To analyze independent influencing factors of surgical textbook outcome (TO) in patients with gallbladder carcinoma, and to establish a nomogram for predicting TO and evaluated the predictive ability.Methods:Patients with gallbladder carcinoma who underwent surgery in Department of Hepatobiliary and Pancreatic Surgery at Dongfang Hospital Affiliated to Shanghai Tongji University and Department of Biliary Tract Surgery Ⅰ, Third Affiliated Hospital of Naval Medical University (Shanghai Eastern Hepatobiliary Surgery Hospital) from January 2013 to December 2018 were included and the clinical features were retrospectively analyzed. A total of 232 patients were included, including 114 males and 118 females, aged (61.0±9.8) years. According to whether TO reached or not, they were divided into TO group ( n=86) and non-TO group ( n=146). Univariate and multivariate logistic regression were used to analyze the independent influencing factors of TO. The predictive nomogram model of TO was constructed. The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive ability of the model, and the consistency of the predictive model was evaluated by the consistency curve graph and the Hosmer-Lemeshow test. Results:The 1-year and 3-years cumulative survival rates of patients with gallbladder carcinoma in the TO group (86.0% and 62.8%) were better than those in the non-TO group (46.6% and 27.3%), and the difference was statistically significant (χ 2=60.74, P<0.001). In multivariate analysis, higher T stage ( OR=0.16, 95% CI: 0.03-0.79, P<0.001) and cervical gallbladder cancer ( OR=0.14, 95% CI: 0.02-0.94, P=0.004) had the greatest negative association with a TO, and the higher the degree of tumor differentiation ( OR=7.08, 95% CI: 1.34-37.56, P=0.001), the easier it is to achieve TO. The ROC curve showed that the area under the curve of the predictive model was 0.84 (95% CI: 0.79-0.90), suggesting that the model had good predictive performance. A nomogram to assess the probability of TO was developed and had good accuracy in both the consistency curve and Hosmer-Lemeshow test (χ 2=5.77, P=0.673). Conclusion:Tumor T stage, tumor differentiation degree and tumor location are independent influencing factors for achieving TO in patients with gallbladder carcinoma after surgery. The nomogram model constructed according to the above conclusions could accurately predict the probability of reaching TO.

Pharmaceutical analysis is a discipline based on chemical, physical, biological, and information technologies. At present, biotechnological analysis is a short branch in pharmaceutical analysis; however, bioanalysis is the basis and an important part of medicine. Biotechnological approaches can provide information on biological activity and even clinical efficacy and safety, which are important characteristics of drug quality. Because of their advantages in reflecting the overall biological effects or functions of drugs and providing visual and intuitive results, some biotechnological analysis methods have been gradually applied to pharmaceutical analysis from raw material to manufacturing and final product analysis, including DNA super-barcoding, DNA-based rapid detection, multiplex ligation-dependent probe amplification, hyperspectral imaging combined with artificial intelligence, 3D biologically printed organoids, omics-based artificial intelligence, microfluidic chips, organ-on-a-chip, signal transduction pathway-related reporter gene assays, and the zebrafish thrombosis model. The applications of these emerging biotechniques in pharmaceutical analysis have been discussed in this review.

Objective: Plant hormones act as chemical messengers in the regulation of plant development and metabolism. The production of ginsenosides in Panax hybrid is promoted by auxins that are transported and accumulated by PIN-FORMED (PIN) and PIN-LIKES (PILS) auxin transporters. However, genome-wide studies of PIN/PILS of ginseng are still scarce. In current study, identification and transcriptional profiling of PIN/PILS gene families, as well as their potential relationship with ginsenoside biosynthesis in Panax ginseng were investigated. Methods: PIN/PILS genes in P. ginseng was identified via in silico genome-wide analysis, followed by phylogenetic relationships, gene structure, and protein profiles investigation. Moreover, previously reported RNA-sequence data from various tissues and roots after infection were utilized for PIN/PILS genes expression pattern analysis. The Pearson's correlation analysis of specific PIN/PILS genes expression level and main ginsenoside contents were taken to reveal the potential relationship between auxin transports and ginsenoside biosynthesis in P. ginseng. Results: A genome-wide search of P. ginseng genome for homologous auxin transporter genes identified a total of 17 PIN and 11 PILS genes. Sequence alignment, putative motif organization, and sub-cellular localization indicated redundant and complementary biological functions of these PIN/PILS genes. Most PIN/PILS genes were differentially expressed in a tissue-specific manner, and showed significant correlations with ginsenoside content correspondingly. Eight auxin transporter genes, including both PIN and PILS subfamily members, were positively correlated with ginsenoside content (cor > 0.60; P-value <0.05). The expression levels of eleven auxin transporter genes were increased dramatically in the early stage (0–0.5 DPI) after Cylindrocarpon destructans infection, accompanied with various overall expression patterns, implying the dynamic auxin transport in response to biotic stress. Conclusion: Based on the results, we speculate that the accumulation or depletion in temporal or spatial manner of auxin by PIN/PILS transporters involved in the regulation of HMGR activity and subsequent ginsenoside biosynthesis.

Objective:To construct a management plan for postoperative paralytic ileus (PI) in spinal surgery patients and explore its effect.Methods:The management plan for PI in spinal surgery patients was constructed based on literature retrieval and expert consultation. From July 2020 to June 2021, 295 patients with spinal surgery of Spine Surgery Department in Yancheng Third People's Hospital were selected by convenience sampling. The patients from January to June 2021 were in the experimental group ( n=152) , and the patients from July to December 2020 were in the control group ( n=143) . The control group adopted routine nursing, while the experimental group received PI management plan of spinal surgery on the basis of routine nursing. We compared the abdominal distension grading, first exhaust time, defecation time, PI incidence, anal exhaust utilization rate, average hospitalization day and patient satisfaction between the two groups at 12, 24, 36, 48, 72 hours after surgery. Results:After intervention, there was no statistical difference in the level of abdominal distension between the two groups at 12, 24 and 36 hours ( P>0.05) . The level of abdominal distension in the experimental group at 48 hours and 72 hours were both lower than that in the control group, and the differences were statistically significant ( P<0.05) . The time of first exhaust and defecation of patients in the experimental group were shorter than that in the control group, and the differences were statistically significant ( P<0.01) . The incidence of PI in the experimental group was lower than that in the control group, with a statistically significant difference ( P<0.05) . The satisfaction of patients in the experimental group was higher than that in the control group, with a statistically significant difference ( P<0.05) . The utilization rate of anal exhaust in the experimental group was higher than that in the control group, with a statistically significant difference ( P<0.05) . There was no statistical difference in average hospitalization days between the two groups ( P>0.05) . Conclusions:PI management plan for patients with spinal surgery can reduce the first exhaust time, defecation time, PI incidence, and improve patient satisfaction, which can provide a basis for standardizing the management of PI for patients with spinal surgery.