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 compare the analgesic effects of fascia iliaca compartment block with different concentrations of liposomal bupivacaine for total hip replacement in elderly patients.Methods:This was a prospective study. Sixty-four elderly patients of either sex with hip fracture, aged 65-85 yr, with body mass index of 20-30 kg/m 2 and American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ, undergoing elective total hip arthroplasty from September to December 2023 in Zhangjiagang Hospital affiliated to Soochow University, were divided into LB1, LB2, LB3 and LB4 groups ( n=16 each) using the random number table method. The fascia iliaca compartment block was performed under ultrasound guidance before anesthesia induction. Liposomal bupivacaine 66.5, 133.0, 199.5 and 266.0 mg diluted to 30 ml in normal saline were given in LB1, LB2, LB3 and LB4 groups, respectively. The consumption of intraoperative sufentanil and remifentanil and tracheal extubation time were recorded. The pain numeric rating scale (NRS) scores at rest and during activity were recorded at 4, 8, 12, 24 and 48 h postoperatively. Parecoxib sodium was intravenously injected when the NRS score≥4, and the use of parecoxib sodium was recorded. The effect of motor nerve block in the affected lower extremity was evaluated using the modified Bromage scale score at 4, 8, 12, 24 and 48 h postoperatively. The first ambulation time and duration of hospitalization were recorded. The scores for patients′ satisfaction with analgesic effects at 48 h after operation and the occurrence of adverse reactions within 48 h after operation were recorded. Results:Compared with LB1 group, the consumption of intraoperative sufentanil and remifentanil was significantly reduced, the tracheal extubation time was shortened, NRS scores at rest at 12, 24 and 48 h after operation and NRS scores during activity at 8, 12, 24 and 48 h after operation were significantly decreased, and the scores for patients′ satisfaction with analgesic effects were increased in LB2, LB3 and LB4 groups, the modified Bromage scale scores were significantly increased at 4 and 8 h after operation, and the first ambulation time and duration of hospitalization were shortened in LB2 group, and the modified Bromage scale scores were significantly increased at 4, 8, 12, 24 and 48 h after operation in LB3 and LB4 groups ( P<0.05). Compared with LB2 group, the modified Bromage scale scores were significantly increased at 12, 24 and 48 h after operation, and the first ambulation time and duration of hospitalization were prolonged in LB3 and LB4 groups ( P<0.05). There was no significant difference in the incidence of postoperative adverse reactions among the four groups ( P>0.05). Conclusions:The optimal concentration of liposomal bupivacaine for fascia iliaca compartment block is 133 mg/30 ml when used for analgesia in elderly patients undergoing total hip replacement.

ObjectiveTo observe the intervention effect of Dahuang Xiezhuo prescription （DHXZ） on inflammation and suppressor of cytokine signaling 3 （SOCS3）/Toll-like receptor 4 （TLR4） pathway in rats with chronic renal failure （CRF）， and to explore its molecular mechanism in alleviating renal inflammatory response. MethodThe 90 male SD rats， 15 were randomly selected as sham group， and the remaining 75 were used as modeling group to replicate CRF rat model by 5/6 nephrectomy. After successful modeling， the rats were randomly divided into model group， DHXZ low-， medium-， high-dose groups （6.825， 13.65， 27.3 g·kg^-1） and Niaoduqing Granules group （2.6 g·kg^-1）. The drug intervention groups received corresponding drugs by gavage for 8 consecutive weeks. After administration， hematoxylin-eosin （HE） staining and Masson staining were used to observe the morphological changes of rat renal tissue， and blood creatinine （SCr）， blood urea nitrogen （BUN） and blood uric acid （UA） were tested. Enzyme-linked immunosorbent assay （ELISA） was performed to detect the serum contents of interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α） and C-reactive protein （CRP）. The mRNA expressions of SOCS3 and TLR4 in renal tissue were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and the protein expressions of SOCS3， TLR4， nuclear transcription factor （NF-κB） and myeloid differentiation factor （MyD88） were detected by Western blot. Immunohistochemistry was used to determine the protein expressions of NF-κB， MyD88， NOD-like receptor protein 3 （NLRP3） and melanoma deficiency factor 2 （AIM2）. ResultCompared with the sham group， the model group had a significant inflammatory response in renal tissue， and an increase in blood SCr， BUN， UTP， IL-6， TNF-α and CRP （P<0.05）. The protein and mRNA expressions of SOCS3 in renal tissue of rats in the model group were lower while the protein expressions of TLR4， NF-κB， MyD88， NLRP3 and AIM2 and the mRNA expression of TLR4 were higher than those in the sham group （P<0.05）. Compared with the model group， DHXZ and Niaoduqing granules groups presented markedly reduced inflammatory response in renal tissue and decreased blood SCr， BUN， UTP， IL-6， TNF-α and CRP （P<0.05）. Additionally， DHXZ and Niaoduqing granules up-regulated the protein and mRNA expressions of SOCS3 in renal tissue while down-regulated the protein expressions of TLR4， NF-κB， MyD88， NLRP3 and AIM2 and the mRNA expression of TLR4 （P<0.05）. ConclusionDHXZ can reduce the release and expression of inflammatory factors， inhibit the inflammatory response and improve renal function， and the mechanism may be related to the regulation of SOCS3/TLR4 signaling pathway.

Objective:To compare the effects of thoracoscopic anatomical segmentectomy and thoracoscopic lobectomy on patients' respiratory function.Methods:Retrospective analysis of 326 patients who underwent thoracoscopic surgery from July 2016 to July 2019(209 patients underwent anatomical segmentectomy, 117 patients underwent lobectomy). According to variables including gender, age, tumor location, smoking history and BMI, two propensity score-matched cohorts including 89 patients respectively were constructed. The patients’ baseline data and respiratory function date of the patients pre-operation and post-operation were analyzed. The measurement data that obey the normal distribution were described by mean±standard deviation, and the t-test was used for comparison between groups; the measurement data of non-normal distribution was described by the median value( P25, P75), and the Wilcoxon rank sum test was used for the comparison between groups; The data was described by frequency, and the chi-square test or Fisher's exact probability method was used for comparison between groups. Results:At the first-month follow-up after surgery, there was no significant difference in the variation of FVC[(0.48±0.40)L vs.(0.34±0.37)L, P=0.215)and FEV1[(0.52±0.46)L vs.(0.43±0.77)L, P=0.364), and in the change rate of FVC(%)[15.23(8.74, 21.25) vs. 14.58(7.75, 19.40), P=0.122], FEV1(%)[17.25(9.56, 22.78) vs. 16.42(9.15, 20.28), P=0.154]and DLCO(%)[18.54(10.88, 25.68)vs. 17.45(9.58, 23.75) P=0.245]. Between the segmentectomy group and lobectomy group, there was a significant difference in the alteration of FVC[(0.50±0.47)L vs. (0.29±0.31)L, P=0.031] and FEV1[(0.44±0.34)L vs.(0.24±0.23)L, P<0.001], the change rate of FVC(%)[14.27(7.87, 22.32) vs. 9.95(5.56, 17.24), P=0.008]、FEV1(%)[15.23(8.36, 22.17)vs. 10.05(5.15, 18.54), P<0.001]and DLCO(%)[13.74(6.24, 19.78) vs. 4.45(-2.32, 13.75), P=0.023]in the 6th month after surgery. The lobectomy group had a higher variation of FEV1[(0.34±0.49)L vs.(0.18±0.26)L, P=0.006] and change rate of FVC(%)[9.28(2.15, 18.94) vs. 5.24(0.52, 11.45), P=0.0032] and FEV1(%)[10.45(3.15, 21.32) vs. 6.50(1.55, 14.24), P<0.001] in the first year after surgery. However, the variation of FVC[(0.29±0.36)L vs.(0.21±0.24)L, P=0.176) and the change rate of DLCO(%)[8.35(2.15, 16.45) vs. 6.23(2.12, 14.54), P=0.143] didn't show a significant difference between the two groups. Conclusion:Whether in the short or the middle postoperative period, segmentectomy can preserve postoperative respiratory function than lobectomy.

Objective : To observe the effect of hydrogen sulfide( H2 S) on the expression of transforming growth factor⁃β1(TGF⁃ β1) , E ⁃cadherin (E⁃CAD) , Vimentin (VIM) , alpha⁃smooth muscle actin ( α ⁃SMA) during epithelial⁃mesenchymal transformation(EMT) , and to explore the anti⁃fibrosis mechanism of it. Methods : Sixty rats ( male SD) were randomly divided into control group, bleomycin group, NaHS + bleomycin group and prednisolone + bleomycin group , 15 rats per group. 5 rats of each group were sacrificed at random in 7th , 14th and 28th day. The degree of alveolitis and pulmonary fibrosis was observed . The expression of protein and mRNA of TGF⁃ β1 , E ⁃cad , VIM , α ⁃SMA were determined by Immunohistochemi stry and RT⁃PCR. Results : ① HE and Masson staining showed that the lung tissue of fibrosis had the lowest degree in control group. and the most severe in bleomycin group. The lung tissue of NaHS + bleomycin group and prednisolone + bleomycin group also had alveolitis and fibrosis changes , but the degree Were significantly less than bleomycin group. ② The mRNA and protein expression levels of TGF⁃ β1 , VIM and α ⁃SMA in bleomycin group, NaHS + bleomycin group and prednisolone + bleomycin group were all higher than that in control group at 7th , 14th and 28th day ( P < 0. 05 ) , while the expression levels of them in NaHS + bleomycin group and prednisolone + bleomycin group were all lower than that in bleomycin groupat each time (P < 0. 05) , which was significant at 28th day in NaHS + bleomycin. ③ The mRNA and protein expression levels of E ⁃Cad in bleomycin group, NaHS + bleomycin group and prednisolone + bleomycin group were all lower than that in control group at 7th , 14th and 28th day(P < 0. 05) , but the expression levels of E ⁃Cad in⁃NaHS + bleomycin group and prednisolone + bleomycin group were higher than that in bleomycin group at each time(P < 0. 05) , which was significant at 28th day in NaHS + bleomycin. Conclusion H2 S can reduce the degree of pulmonary fibrosis in rats , its mechanism may be related to the down⁃regulation of TGF⁃ β1and the inhibition of the EMT , which can enhance the expression of E ⁃cad and reduce the expression of TGF⁃ β1 , VIM and α ⁃SMA.

Objective    To assess the correlation of WHO pathological classification and Masaoka stage of thymomas with its prognosis. Methods    A total of 468 patients with thymomas who received surgeries during 2009-2019 in Huashan Hospital, Fudan University, were collected. There were 234 males and 234 females with an average age of 21-83 (49.6±18.7) years. A total of 132 patients underwent video-assisted thoracic surgery (VATS) and 336 patients underwent thymectomy with median sternal incision. The follow-up time was 5.7±2.8 years. The clinical data of the patients were analyzed. Results    The amount of intraoperative bleeding was 178.3±133.5 mL in the median sternal incision group, and 164.8±184.1 mL in the VATS group (P=0.537). The operative time was 3.3±0.7 h in the median sternal incision group and 3.4±1.2 h in the VATS group (P=0.376). Postoperative active bleeding, phrenic nerve injury and chylothorax complications occurred in 8 patients, 9 patients and 1 patient in the VATS group, respectively, and 37 patients, 31 patients and 7 patients in the median sternal incision group, respectively. There was no statistical difference between the two groups (P=0.102, 0.402, 0.320). The 5-year cumulative progression free survival (PFS) rates of patients with WHO type A, AB, B1, B2, B3 and C thymomas were 100.0%, 100.0%, 95.7%, 81.4%, 67.5% and 50.0%, respectively (P<0.001). The 5-year PFS rates of patients with Masaoka stageⅠ-Ⅳ thymomas were 96.1%, 89.2%, 68.6% and 19.3%,  respectively (P<0.001). The 5-year PFS rate was 87.3% in patients with myasthenia gravis (MG) and 78.2% in patients without MG (P<0.001). The 5-year PFS rates of patients with different surgeries were 82.4% and 83.8%, respectively (P=0.904). Conclusion    WHO pathological classification and Masaoka stage have significant clinical prognosis suggestive effect. Thymoma patients combined with MG have better prognosis, which suggests early diagnosis and treatment of thymoma are important.

Objective To explore the clinical application effect of squamous cell carcinoma antigen (SCC) ,cancer embryo antigen (CEA) and carbohydrate antigen 125(CA125) chemiluminescence combined detection in early diagnosis of lung cancer .Methods The SCC ,CEA and CA125 levels in the patients with early stage lung cancer ,benign lung diseases and healthy subjects undergoing physical examination were detected by using the automatic chemiluminescence immune analyzer .Results The concentrations of three tumor markers in the lung cancer group were significantly higher than those in the benign disease group and control group (P<0 .05);t he concentrations of CEA and CA125 in the adenocarcinoma patients with were significantly higher than those in the patients with squamous cell carcinoma and small cell carcinoma (P<0 .05) .The concentration of SCC in the patients with squamous cell carcinoma was significantly higher than that in the patients with adenocarcinoma and small cell lung cancer (P<0 .05) .The sen-sitivity ,specificity ,positive predictive value and negative predictive value of combined detection of three tumor markers were signifi-cantly better than that of single tumor marker ,and the difference was statistically significant (P<0 .05) .Conclusion The combined detection of SCC ,CEA and CA125 can be used in the early diagnosis of lung cancer and has the promotion value .

Objective To analyze the relationship between the expression of protection of telomeres 1 (POT1) and the pathogenesis of acute myeloid leukemia (AML). Methods 62 patients with de novo AML (case group) and 10 patients with iron deficiency anemia (control group) were enrolled in this study. The quantitative real-time polymerase chain reaction (PCR) and Western blot were used to detect the expression of POT1 in AML patients. Results There were 62 de novo AML patients, including 2 cases M1, 14 cases M2, 12 cases M3, 14 cases M4, 17 cases M5, 2 cases M6 and 1 case AML without classification. According to the risk stratification, high risk group (24 cases), medium risk group (22 cases) and low risk group (16 cases) were divided. Compared with that in the controls, POT1 expression levels in patients with AML were significantly decreased both in mRNA and protein level (P< 0.05). The relative expression levels of POT1 mRNA and protein in patients with M2, M4 and M5 were significantly lower than those in the controls (P< 0.05). The expression levels of POT1 in high risk group, medium risk group and low risk group were significantly decreased than those in the controls (P<0.05). Compared with that in the controls, The relative POT1 mRNA expression was significantly decreased in M3 patients (P< 0.05), but not in protein level. POT1 protein expression was showed both in the cytoplasm and nucleus. There was no significant difference of the expression of POT1 protein between cytoplasm and nucleus (P> 0.05). Conclusions POT1 may be involved in the pathogenesis of AML. POT1 protein expresses in both cytoplasm and nucleus, and the regulatory mechanism may be related to the telomere length.

Objective To explore whether 5 to -7-day of folic acid supplementation prior to pemetrexed therapy is needed. Methods We retrospectively evaluate the outcomes of non-small cell lung cancer patients received less than the advised folic acid premedication. Seventy patients with Ⅲ-Ⅳ NSCLC were randomly divided into two groups: patients who initiated vitamin supplementation on 7 days before the first dose of pemetrexed (group A) and patients who initiated vitamin supplementation on the day of the first dose of pemetrexed (group B). Results In group A and group B, CR 0 and 0, PR 10 and 8, the response rates of 28.6% and 22.9% were observed, respectively. There was no statistically significant differences between these two groups. No significant differences were observed in the incidence of hematologic and non-hematologic toxicities. Conclusions The initiation of pemetrexed-based chemotherapy does not need to accommodate a vitamin supplementation schedule.

Objective To investigate the relationship between genetic variants in the Toll-like receptor (TLR) pathway genes and susceptibility of gastric cancer (GC) and esophageal squamous cell carcinoma (ESCC).Methods The data of whole genome association studies of the high-risk population of GC and ESCC in China were analyzed by adaptive rank-truncated product (ARTP) method in pathway and gene level.The associations between single nucleotide polymorphism (SNP) and susceptibility of GC and ESCC were analyzed with additive model of unconditional Logistic regressions.PLINK 1.07 and SPSS 19.0 software were performed for statistical analyses,and ARTP package in R3.0.2 was used for pathway and gene level analysis.Results In gene-level analyses,eight genes were found to be associated with susceptibility of GC (P ＜0.05) and six genes were associated with susceptibility of ESCC (P ＜ 0.05).In single SNP-level analyses,21 SNPs were statistically correlated with susceptibility of GC (P ＜ 0.01),and 11 SNPs were statistically correlated with susceptibility of ESCC (P ＜0.01).Conclusions Some genetic variants in TLR pathway are associated with risk of GC and ESCC.The potential molecular mechanisms need further investigation.