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 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.

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 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.

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: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.

Objective:To explore the value of lactic acid (Lac), procalcitonin (PCT), sequential organ failure assessment (SOFA) score and acute physiology and chronic health evaluationⅡ (APACHEⅡ) score in assessing the severity and predicting the prognosis in sepsis shock.Methods:A retrospectively study was conducted. Patients with septic shock hospitalized in the department of critical care medicine of the Affiliated Hospital of Jining Medical University from April 2015 to June 2019 were enrrolled. The patient's gender, age, body mass index (BMI), infection site, organ dysfunction status; Lac, PCT, C-reactive protein (CRP), heart rate and body temperature immediately after admission to the intensive care unit (ICU); APACHEⅡ and SOFA scores within 24 hours, and 28-day prognosis were collected. According to the 28-day prognosis, the patients with septic shock were divided into the survival group and the death group, and the differences in the indicators between the groups were compared. Multivariate Logistic regression analysis was used to screen the risk factors of 28-day death in patients with septic shock; receiver operating characteristic curve (ROC curve) was used to analyze the value of Lac, PCT, SOFA, APACHEⅡ, and age in predicting the 28-day prognosis of patients with septic shock.Results:A total of 303 septic shock patients were enrolled, of which 124 cases survived and 179 died on the 28th day, and the 28-day mortality was 59.08%. ① Compared with the survival group, patients in the death group were older (years old: 66.58±15.22 vs. 61.15±15.68), APACHEⅡ, SOFA, proportion of lung infections, Lac increased [APACHEⅡ score: 22.79±7.62 vs. 17.98±6.88, SOFA score: 9.42±3.51 vs. 5.65±1.59, proportion of lung infections: 53.63% (96/179) vs. 39.52% (49/124), Lac (mmol/L): 5.10±3.72 vs. 3.71±2.56], oxygenation index (PaO 2/FiO 2) and ICU body temperature decreased [PaO 2/FiO 2 (mmHg, 1 mmHg = 0.133 kPa): 198.94±80.15 vs. 220.68±72.06, ICU body temperature (℃): 37.47±1.08 vs. 37.80±1.14], and the differences were statistically significant (all P < 0.05).②Multivariate Logistic regression analysis results: after adjusted for potential confounding factors, APACHEⅡ, PCT, Lac, age and SOFA were independent risk factors for death in patients with septic shock [APACHEⅡ: odds ratio ( OR) =1.05, 95% confidence interval (95% CI) was 1.01-1.10, P = 0.039; PCT: OR = 0.99, 95% CI was 0.98-1.00, P =0.012; Lac: OR = 1.23, 95% CI was 1.08-1.40, P = 0.002; age: OR = 1.03, 95% CI was 1.01-1.05, P =0.009; SOFA score: OR =1.88, 95% CI was 1.59-2.22, P < 0.001]. ③ROC curve analysis showed that APACHEⅡ, Lac, age and SOFA could predict the prognosis of patients with septic shock [APACHEⅡ: the area under the ROC curve (AUC) = 0.682 4, 95% CI was 0.621 7-0.743 1, P = 0.000; when the best cut-off value was 18.500, its sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio were 72.63%, 54.84%, 69.89%, 58.12%, 1.608 1 and 0.499 2, respectively. Lac: AUC = 0.604 5, 95% CI was 0.540 8-0.668 2, P = 0.002; when the best cut-off value was 3.550 mmol/L, the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio were 50.84%, 73.39%, 73.39%, 50.94%, 1.910 3 and 0.669 9, respectively. Age: AUC = 0.599 1, 95% CI was 0.535 4-0.662 7, P = 0.003; when the best cut-off value was 72.500 years old, the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio were 42.46%, 75.00%, 71.03%, 47.45%, 1.698 3 and 0.767 2, respectively. SOFA: AUC =0.822 3, 95% CI was 0.776 7-0.867 9, P = 0.000; when the best cut-off value was 7.500, its sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio were 68.72%, 87.90%, 89.13%, 66.06%, 5.680 4, 0.355 9 respectively]. The combined prediction had a good sensitivity (72.63%) and specificity (84.86%), and AUC (0.876 5) was higher than that of a single variable, suggested that the multivariate combination was more accurate in predicting the short-term outcome of septic shock. Conclusion:Lac, PCT, SOFA score, APACHEⅡ score and age were independent risk factors for death in patients with septic shock, and the accuracy of Lac, SOFA score, APACHEⅡ score and age in predicting short-term prognosis of septic shock was better than that of single variable, and the diagnostic value was higher.

Objective: To investigate the quantitative relationship between liver fat content and bone mineral density (BMD) in middle-aged and elderly people. Methods: Totally 184 middle-aged and elderly community residents were recruited from March to June 2016, including 68 males and 116 females. MRI mDIXON-Quant and quantitative CT (QCT) examinations were performed to determine the content of liver fat and L1-L3 vertebral BMD. The subjects were divided into four groups according to the quartiles of liver fat content, and the baseline characteristics and other variables of different groups were were identified by using one-way analysis of Variance. The relationship between liver fat content and lumbar vertebral BMD was assessed with Spearman correlation and partial correlation analysis. Result: Subjects with higher hepatic fat content had lower spine BMD and higher body mass index (BMI), waist circumference. Liver fat content was negatively correlated with BMD (r=-0.203, P=0.003). After age and body weight were controlled, the negative correlation between liver fat content and BMD was still significant (r=-0.291, P<0.001), in males (r=-0.283, P=0.021) and in females (r=-0.210, P=0.025). Conclusion Liver fat content is negatively correlated with lumbar vertebral BMD in middle-aged and elderly people.

Objective: To study the correlation of the degree of sleep apnea with arrhythmia, heart rate variability(HRV)and blood pressure variability(BPV)in elderly patients with obstructive sleep apnea hypopnea syndrome(OSAHS), and to investigate the intervention effects of home-based continuous positive airway pressure(CPAP)treatment. Methods: A total of 122 elderly hypertension patients with OSAHS were recruited in the prospective study.Patients were divided into three groups according to the sleep apnea hypopnea index(apnea hypopnea index, AHI): the mild OSAHS group(5 times/h≤AHI≤15 times/h, n=42), moderate OSAHS group(15 times/h30 times/h, n=40). All patients took ambulatory electrocardiogram and ambulatory blood pressure examinations before and after three months of CPAP treatment.The incidences of arrhythmia, HRV and BPV indexes of each group before and after CPAP treatment were compared between the groups. Results: The incidences of premature atrial contraction, atrial tachycardia and premature ventricular beats were higher in the moderate and severe OSAHS groups than in the mild OSAHS group(P<0.01). Compared with the mild OSAHS group, the RR interval standard deviation(SDNN), root mean square of successive differences(rMSSD), proportion of patients with consecutive RR-interval differences greater than 50 ms(PNN5), standard deviation of the averaged normal RR intervals for all 5 min segments and deceleration capacity of rate increased in the moderate and severe OSAHS groups(P<0.05), and the increases were more obvious in the severe group.Compared with the mild OSAHS group, the standard deviation of 24-h systolic blood pressure, standard deviation of 24-h diastolic blood pressure, standard deviation of daytime systolic blood pressure, standard deviation of nighttime systolic blood pressure and incidence of non-dipper hypertension increased in the moderate and severe OSAHS groups(P<0.05), with the increases were more obvious in the severe group, and the differences was significant between the moderate and severe OSAHS groups(P<0.05). HRV and BPV indicators improved except for high frequency(HF)/low frequency(LF)in all groups(P<0.05)after home treatment of CPAP, and the improvement was more obvious in the severe group.The incidence of non-dipper circadian rhythm of blood pressure improved more significantly in the severe OSAHS group than in the moderate OSAHS group. Conclusions With aggravated sleep apnea, the incidences of arrhythmias such as premature atrial contraction, atrial tachycardia, and premature ventricular contraction are increased and the HRV and BPV are enlarged in elderly hypertension patients complicated with OSAHS.The home treatment of CPAP can improve the above indicators, and it is an effective way to treat OSAHS complicated by hypertension in elderly patients.

Objective: To investigate the effect of Yi Jin Jing (Sinew-transforming Qigong Exercises) plus tuina on scapulohumeral periarthritis (SP). Methods: A total of 30 cases with SP were randomized into an observation group and a control group. Those in the observation group practiced Yi Jin Jing (Sinew-transforming Qigong Exercises) plus tuina therapy; whereas those in the control group received only tuina therapy. Tuina therapy was conducted every other day, 20 min every time for 1 month and Yi Jin Jing (Sinew-transforming Qigong Exercises) was conducted once a day for 1 month. The therapeutic effects were assessed by visual analogue scale (VAS) and Constant-Murley scale. Results: After treatment, the VAS score and Constant-Murley scale were substantially improved, showing statistical significances (P<0.01); the Constant-Murley scale in the observation group was better than that in the control group, showing a statistical significance (P<0.01); the effective rate in the observation group was higher than that in the control group, between-group comparison showed a statistical significance (P<0.01). Conclusion: Yi Jin Jing (Sinew-transforming Qigong Exercises) plus tuina and tuina alone have a verified effect in treating SP, and the former can achieve a better effect than the later.