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In this open-label, single-arm, phase I/II clinical trial, we evaluated the efficacy of anti-B cell maturation antigen (BCMA) chimeric antigen receptor (CAR)-T cell (HDS269B) therapy in 49 relapsed/refractory multiple myeloma (RRMM) patients, including 20 with Eastern Cooperative Oncology Group (ECOG) grade 3-4. After HDS269B infusion (9 × 10

Balloon angioplasty with or without stent placement has become the mainstream treatment of Budd-Chiari syndrome (BCS). Restenosis of hepatic vein (HV) is a tough problem. The aim of this study was to perform a meta-analysis to compare the restenosis in HV involvement type BCS patients treated by balloon dilatation with versus without stent. Meta-analysis was used to calculate the combined effect size and their 95% confidence intervals (CI), based on random effect; and calculate the risk ratio (RR) and its 95% CI based on fixed effect. The publication bias was assessed by funnel plot and Begg's test. Sixteen studies were selected for meta-analysis. One thousand and eighty-two patients (1,019 from Asian, 63 from non-Asian countries) were included. Seven hundred and five of 1,019 (69%) Asian patients received HV balloon dilatation alone. RR value (RR=0.85, 95% CI 0.68-1.08) of the two groups was obtained through meta-analysis, which meant that the risk of restenosis in balloon dilatation alone group was 15% lower than that in combined with stent placement group; although there was no significant statistical difference between two groups (p=0.178). The current meta-analysis indicated that balloon dilatation alone is first preferred approach in Asian BCS patients compared to the non-Asian patients. Balloon dilatation combined with stent placement does not reduce restenosis risk over balloon dilation alone in the treatment of BCS with HV occlusion. It is suggested that stent should be used cautiously for such patients. Key Words: Balloon dilatation, Budd-Chiari syndrome, Stent, Restenosis, Meta-analysis.

To estimate the safety and efficacy of transcatheter arterial embolization (TAE) in the treatment of refractory hematuria of prostatic origin (RHPO).This retrospective study included 23 patients who underwent TAE for RHPO between May 2013 and August 2021. Technical and clinical success rates were calculated, and arteriogram findings and complications were detected.Embolization was performed 24 times in 23 patients. Technical success was achieved in 24/24 (100%) embolization procedures. Contrast agent extravasation was detected during 2 of the 24 angiographic procedures. Bilateral embolization was performed in 23 (95.8%) of the 24 procedures. The clinical success rate was 21/23 (91.3%), and hematuria stopped 1-4 days after TAE. No serious complications were observed.TAE is a safe and effective minimally invasive technique for treating patients with RHPO.

Bone marrow-derived mesenchymal stem cells (BMSCs) can differentiate into hepatocyte-like cells (HLCs) to attenuate cirrhosis. Long noncoding RNA (lncRNA) SNHG1 has been demonstrated to orchestrate BMSC differentiation, whereas its role in cirrhosis remains elusive. Therefore, this study was performed to figure out whether lncRNA SNHG1 was involved in cirrhosis by affecting HLC differentiation of BMSCs. Mouse BMSCs were isolated, and the BMSC differentiation into HLCs was induced by hepatocyte growth factor (HGF). A cirrhotic mouse model was established using carbon tetrachloride and phenobarbital, followed by intravenous injection of BMSCs with manipulated expression of lncRNA SNHG1, microRNA (miR)-15a, and SMURF1. Subsequent to HGF induction, expression of hepatocyte-related genes, albumin secretion, and glycogen accumulation was increased in BMSCs, suggesting the differentiation of BMSCs into HLCs. Mechanistically, lncRNA SNHG1 bound to miR-15a that targeted SMURF1, and SMURF1 diminished ATG5 and Wnt5a expression by enhancing the ubiquitination of UVRAG. LncRNA SNHG1 or SMURF1 silencing or miR-15a overexpression promoted differentiation of BMSCs into HLCs and repressed cirrhosis of mice by upregulating ATG5 and Wnt5a via UVRAG. Conclusively, lncRNA SNHG1 silencing might facilitate HLC differentiation from mouse BMSCs and alleviate cirrhosis via the miR-15a/SMURF1/UVRAG/ATG5/Wnt5a axis.

Background This study was performed to compare the advantage and disadvantage of posterolateral approach (PLA) and direct anterior approach (DAA) in total hip arthroplasty (THA). Methods Relevant trials were identified via a search of the Cochrane Central Register of Controlled Trials and PubMed from inception to 1 June 2019. A meta-analysis was performed to compare postoperative perioperative and radiographic outcomes between DAA and PLA in THA with respect to the hospital stay, blood loss, incision length, operative time, complications, and femoral and cup component position. The Harris Hip Score (HHS) was also assessed before and after 6 months postoperatively. Results Nine eligible studies involving 22698 adult patients (DAA group, n = 2947; PLA group, n = 19751) were identified for analysis. Compared with the PLA group, the DAA group had shorter hospital stay and achieved better HHS within 6 months after operation (P < 0.05), but the HHS was no significant differences between the two groups over 6 months (P > 0.05). The DAA group had significantly longer operative time, more blood loss, and complications than the PLA group (P < 0.05). In addition, the femoral component positioned in neutral and cup component inclination angle was comparable between both groups (P > 0.05); however, cup component anteversion angle was significantly larger in the PLA group (P < 0.05). Conclusion Patients in the DAA group had higher HHS within 6 months and shorter hospital stay. The DAA could offer rapid early functional recovery after THA compared with the PLA. However, the DAA group often required longer operative time and had more blood loss. Furthermore, there was a higher early complication rate. Therefore, we believe that the direct anterior approach was a more difficult technique. The surgeon should be a well-trained joint surgeon with extensive prior hip replacement experience before performing THA through a DAA, and DAA was not suitable for beginners performing THA. In addition, we did not observe the difference with regard to the femoral component position and cup component inclination angle except for the smaller cup component anteversion angle in DAA group.

Purpose To explore the dynamic changes and correlation between CT imaging manifestations and cellular immunity of COVID-19. Materials and methods This retrospective review analyzed 23 patients with COVID-19, including 13 males and 10 females aged 27–70 years, with an average age of 48 years. Patients were divided into two groups: group A with 11 critical-severe patients, and group B with 12 common-mild patients. Clinical, laboratory, and radiological data were collected and analyzed. Results LYM, LYM (%), CD3+, CD4+, and CD8+ decreased, while NEU (%), CRP, and CT scores increased in all patients, WBC in group A increased. In group A, on day 10–12 after disease onset, CT scores and CRP reached the highest point, and day 13–15 LYM, LYM (%) reached the lowest but NEU (%) and WBC reached the highest, CD3+, CD4+ and CD8+ were at the lowest on day 10–15. In group B, on day 7–9, CT scores, NEU (%) and CRP reached the peak, but LYM, LYM (%), CD3+, CD4+ and CD8+ reached the lowest. In all patients, CT scores had a significantly negative correlation with CD3+, CD4+, CD8+, LYM (%), and LYM (p = 0.001, r = − 0.797; p = 0.008, r = − 0.698; p = 0.002, r = − 0.775; p

Objective To evaluate the clinical and radiographic outcomes of total knee arthroplasties (TKA) between using medial-pivot (MP) and posterior-stabilized (PS) prosthesis. Does MP prosthesis and PS prosthesis influence the clinical results of a TKA? Methods An electronic literature search of PubMed Medline and the Cochrane Library was performed from inception to October 1, 2019. A meta-analysis to compare postoperative outcomes of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, Knee Society Score (KSS), range of motion (ROM), complications, and radiographic results between MP and PS prosthesis were conducted. Results Seven eligible studies involving 934 adult patients (MP group, n = 461; PS group, n = 473) were identified for analysis. This study showed no significant difference between the 2 groups in the WOMAC scores, KSS, ROM, and complications (P > .05). The differences of the femorotibial angle, position of implant, and patellar tilt were also not significant between the 2 groups (P > .05). Conclusion The present meta-analysis has shown that patients with the MP prosthesis have similar clinical results as patients with PS prosthesis. Furthermore, the radiographic results, especially patella tilt angle, were also similar between the 2 groups. Therefore, surgeons should be aware that the types of prostheses are not a decisive factor to ensure successful operation.

Background and objective: as COVID-19 has triggered enormous human casualties and disastrous economic loss, the strategies to contain its spread are urgently needed. We aim to assess the value of our suspect case strategy on COVID-19 cases detection and ensure it to be a complement to the RT-PCR test. Materials and methods: from January 23 to April 30, 2020, patients admitted to our emergence isolation ward (EIW) were analyzed in this study. With RT-PCR as a reference standard, all participants were assigned to COVID-19 positive and negative groups. We compared the performance of the suspect case strategy, WBC, LYM, and chest radiography on COVID-19 detection. Results: one hundred twenty-five cases were analyzed in the study period. The receiver operating characteristic (ROC) curve revealed the sensitivity of WBC and LYM on COVID-19 detection was 92.11% and 76.31%, respectively. The sensitivity of the suspect case was 94.73%, and the sensitivity of chest CT was 53.33%. Statistically significant differences were observed for the suspect case, WBCs, LYM, and chest CT on COVID-19 detection. Discussion: suspect case strategy can help identify false negative RT-PCR tests and be a useful complement to RT-PCR in some countries with a tremendous shortage of RT-PCR agents and specialized laboratory during the COVID-19 outbreak.

Ras homolog family member A (RhoA) has been reported to be involved in numerous biological processes; however, the effects of RhoA on acute lung injury (ALI) have yet to be reported. The present study aimed to explore how RhoA affects cell viability, reactive oxygen species (ROS) activity and cell apoptosis in a cell model of lipopolysaccharide (LPS)‑induced ALI. An MTT assay, flow cytometry, reverse transcription‑quantitative polymerase chain reaction and western blotting were used to determine the effects of RhoA on cell viability, apoptosis and ROS activity. The results demonstrated that RhoA inactivation was able to promote cell viability, and decrease apoptosis and ROS activity of LPS‑treated cells. The results of western blotting indicated that RhoA activated the downstream Wnt/β‑catenin signaling pathway and inhibited the expression of apoptotic factors. These findings suggested that RhoA may be involved in ALI progression and could be a novel therapeutic target for this disease.

Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is thought to regulate the replication of viral RNA and the assembly of virus particles in a serine/threonine phosphorylation-dependent manner. However, the host kinases that phosphorylate NS5A have not been fully identified. Here, we show that HCV particle assembly involves the phosphorylation of NS5A by the c-Abl tyrosine kinase. Pharmacological inhibition or knockdown of c-Abl reduces the production of infectious HCV (J6/JFH1) particles in Huh-7.5 cells without markedly affecting viral RNA translation and replication. NS5A is tyrosine-phosphorylated in HCV-infected cells, and this phosphorylation is also reduced by the knockdown of c-Abl. Mutational analysis reveals that NS5A tyrosine phosphorylation is dependent, at least in part, on Tyr(330) (Tyr(2306) in polyprotein numbering). Mutation of this residue to phenylalanine reduces the production of infectious HCV particles but does not affect the replication of the JFH1 subgenomic replicon. These findings suggest that c-Abl promotes HCV particle assembly by phosphorylating NS5A at Tyr(330).

Ship block construction space is an important bottleneck resource in the process of shipbuilding, so the production scheduling optimization is a key technology to improve the efficiency of shipbuilding. With respect to ship block construction space scheduling problem, a hybrid heuristic algorithm is proposed in this paper. Firstly, Bottom-Left-Fill (BLF) process is introduced. Next, an initial solution is obtained by guiding the sorting process with corners. Then on the basis of the initial solution, the simulated annealing arithmetic (SA) is used to improve the solution by offering a possibility to accept worse neighbor solutions in order to escape from local optimum. Finally, the simulation experiments are conducted to verify the effectiveness of the algorithm.

With respect to the block assembly schedule in a shipbuilding enterprise, a spatial resource constrained project scheduling problem (SRCPSP) is proposed, which aims to minimize the makespan of a project under the constraints of the availability of a two-dimensional spatial resource and the precedence relationship between tasks. In order to solve SRCPSP to the optimum, a branch and bound algorithm (BB) is developed. For the BB-SRCPSP, first, an implicitly enumerative branch scheme is presented. Secondly, a precedence based lower bound, as well as an effective dominance rule, is employed for pruning. Next, a heuristic based algorithm is used to decide the order of a node to be selected for expansion such that the efficiency of the algorithm is further improved. In addition, a maximal space based arrangement is applied to the configuration of the areas required each day in an available area. Finally, the simulation experiment is conducted to illustrate the effectiveness of the BB-SRCPSP.

A series of meso -thienyl porphyrins were synthesized through Lindsey's procedure and characterized. Compared with H 2 TPP (tetraphenylporphyrin), the absorption and fluorescence spectra of thienyl porphyrins have red shift obviously which show that thienyl substituents at meso -position change the electronic structure of tetrapyrrole ring. With protonation using CF 3 COOH, the absorption bands of thienyl porphyrins are further red shifted. The absorption bands of meso -thienyl porphyrins change correspondingly with the variation of solvents’ properties, however the maxima emission wavelengths corresponding to Q * have little relation with solvents. And the fluorescence lifetime become so less even to 1.1 ns. The half-wave redox potential shows cathodic shift relative to H 2 TPP. These changes above are all ascribed to the introduction of thienyl group at meso -position and the possibility of more planarity of meso -thienyl porphyrins for the small size of thienyl group which is helpful to the extending π-delocalization of thienyl groups to the tetrapyrrole ring.

The insulin receptor (INSR), which is an indispensable component of the insulin-signalling pathway, could be a plausible candidate gene for polycystic ovary syndrome (PCOS). This study was designed to determine whether an association exists between three SNP variants (rs3786681, rs17253937 and rs2252673) of the INSR gene and PCOS in Han Chinese. A total of 224 family trios (672 participants in total) were enrolled in this family-based transmission disequilibrium test. Genotypes were obtained by sequencing. A weak association was detected in rs2252673 (P = 0.027), which indicated that INSR may confer an increased susceptibility to PCOS in Chinese. Additionally, the association between INSR gene variants and clinical and metabolic characteristics of women with PCOS was investigated. Carriers of the CG and GG genotypes in women with PCOS were slightly associated with higher cholesterol concentration (t = 2.072, P = 0.048) and lower high-density lipoprotein cholesterol concentration (t = 2.274, P = 0.026). The minor allele conferred increased odds of PCOS independently of body mass index. The present data may provide a basis for further studies of the role of the INSR in the aetiology of PCOS.

Background and Purpose— We tested the hypothesis that circulating microRNAs (miRNAs) present in plasma might display a specific signature in patients with intracerebral hemorrhage. Methods— Global miRNA profiles were determined with the Agilent Human miRNA Microarray platform, and validated by quantitative polymerase chain reaction. Results— A subset of 30 miRNAs were selectively upregulated in both male and female patients with intracerebral hemorrhage. Network analysis revealed that the most significantly overrepresented biological process associated with these miRNAs was inflammation. Unlike the plasma miRNAs in healthy controls, which were detected exclusively in the microvesicle fraction, the deregulated plasma miRNAs after intracerebral hemorrhage were present in both the microvesicle and the supernatant fractions. Conclusions— Intracerebral hemorrhage altered both the abundance and the compartmentalization of several inflammation-related miRNAs in plasma.

Hepatitis C virus (HCV) infects B lymphocytes and induces mixed cryoglobulinemia and B cell non-Hodgkin's lymphoma. The molecular mechanism for the pathogenesis of HCV infection-mediated B cell disorders remains obscure. To identify the possible role for HCV nonstructural 5A (NS5A) protein in B cells, we generated the stable B cell lines expressing Myc-His tagged NS5A. Immunoprecipitation study in the presence or absence of pervanadate (PV) implied that NS5A was tyrosine phosphorylated by pervanadate (PV) treatment of the cells. Therefore we examined pull-down assay by using glutathione S-transferase (GST)-fusion proteins of various Src homology 2 (SH2) domains, which associates with phosphotyrosine within a specific amino acid sequence. The results showed that NS5A specifically bound to SH2 domain of Fyn from PV-treated B cells in addition to Src homology 3 (SH3) domain. Substitution of Arg(176) to Lys in the SH2 domain of Fyn abrogated this interaction. Deletion mutational analysis demonstrated that N-terminal region of NS5A was not required for the interaction with the SH2 domain of Fyn. Tyr(334) was identified as a tyrosine phosphorylation site in NS5A. Far-western analysis revealed that SH2 domain of Fyn directly bound to NS5A. Fyn and NS5A were colocalized in the lipid raft. These results suggest that NS5A directly binds to the SH2 domain of Fyn in a tyrosine phosphorylation-dependent manner. Lastly, we showed that the expression of NS5A in B cells increased phosphorylation of activation loop tyrosine in the kinase domain of Fyn. NS5A containing ligand for both SH2 and SH3 domains enhances an aberrant autophosphorylation and kinase activity of Fyn in B cells.

To determine the association of polymorphism of codon 121 in the ecto-nucleotide pyrophophastase/phosphodiesterase 1 (E-NPP1/PC-1) gene in Chinese women with polycystic ovary syndrome (PCOS).A total of 51 PCOS patients and 61 healthy women from the Chinese Han population from the Center Reproductive Medicine of Provincial Hospital affiliated to Shandong University from June 2005 to July 2006 were recruited for the determination of the polymorphism of the E-NPP1/PC-1 gene. Genomic DNA was extracted from peripheral blood monocytes of patients and controls, and genotyping of the gene was performed by using polymerase chain reaction, which was followed by sequencing.The frequency of the 121Q allele was 13 and 18%, respectively, in PCOS patients and healthy women, while the frequency of the 121K allele was 87 and 82% in the 2 groups. There is no significant difference in the E-NPP1/PC-1 polymorphism between PCOS patients and healthy controls among Chinese Han women.Ecto-nucleotide pyrophophastase/phosphodiesterase 1 polymorphism has no association with PCOS. Further studies are still needed to elucidate whether or not the E-NPP1/PC-1 gene has a functional role in PCOS.