Development and external validation of a machine-learning based model to predict pre-sarcopenia in MASLD population: results from NHANES 2017-2018.

INTRODUCTION AND OBJECTIVES: With rising prevalence of pre-sarcopenia in metabolic dysfunction-associated steatotic liver disease (MASLD), this study aimed to develop and validate machine learning-based model to identify pre-sarcopenia in MASLD population. MATERIALS AND METHODS: A total of 571 MASLD subjects were screened from the National Health and Nutrition Examination Survey 2017-2018. This cohort was randomly divided into training set and internal testing set with a ratio of 7:3. Sixty-six MASLD subjects were collected from our institution as external validation set. Four binary classifiers, including Random Forest (RF), support vector machine, and extreme gradient boosting and logistic regression, were fitted to identify pre-sarcopenia. The best-performing model was further validated in external validation set. Model performance was assessed in terms of discrimination and calibration. Shapley Additive explanations were used for model interpretability. RESULTS: The pre-sarcopenia rate was 17.51% and 15.16% in NHANES cohort and external validation set, respectively. RF outperformed other models with area under receiver operating characteristic curve (AUROC) of 0.819(95%CI: 0.749, 0.889). When six top-ranking features were retained as per variable importance, including weight-adjusted waist, sex, race, creatinine, education and alkaline phosphatase, a final RF model reached an AUROC being 0.824(0.737, 0.910) and 0.732(95%CI: 0.529, 0.936) in internal and external validation sets, respectively. The model robustness was proved in sensitivity analysis. The calibration curve and decision curve analysis confirmed a good calibration capacity and good clinical usage. CONCLUSIONS: This study proposed a user-friendly model using explainable machine learning algorithm to predict pre-sarcopenia in MASLD population. A web-based tool was provided to screening pre-sarcopenia in community and hospitalization settings.

CT-guided microcoil versus hook-wire localization of pulmonary nodule prior to video-assisted thoracoscopic surgery without fluoroscopic guidance.

BACKGROUND: Both microcoils and hook-wires are commonly utilized for preoperative pulmonary nodule localization due to their convenience, but it remains unclear which one should be prioritized for recommendation. AIMS: To compare the safety and efficacy of microcoils and hook-wires for pulmonary nodule localization. METHODS: From January 2021 to December 2021, 310 consecutive patients (113 males and 197 females) with 341 pulmonary nodules who underwent CT-guided microcoil or hook-wire localization prior to video-assisted thoracoscopic surgery (VATS) at our center were retrospectively included in this study. There were 161 patients in the microcoil group and 149 patients in the hook-wire group. The successful localization rate, complication rate, radiation exposure, and medical costs were compared between the two groups. RESULTS: A total of 341 pulmonary nodules were localized, with a success rate of 99% (180/184) in the microcoil group and 93% (146/157) in the hook-wire group, respectively. All patients successfully underwent VATS. Multivariate analysis revealed that hook-wire localization, shorter needle depth into the lung tissue and the longer waiting time from localization to VATS were the risk factors for the localization failure. The incidences of pneumothorax in the microcoil group and hook-wire group were 34.8% (56/161) and 34.9% (52/149), respectively (P = 0.983). The incidences of pneumorrhagia were 13% (24/184) and 46.5% (73/157), respectively (P = 0.000). Multivariate analysis revealed that hook-wire localization and greater depth of needle penetration into lung tissue were risk factors for pneumorrhagia. CONCLUSION: Microcoil localization of pulmonary nodules is superior to hook-wire localization in terms of efficacy and safety. This finding provides insight into priority and broader promotion of microcoil localization.

Paclitaxel inhibits hepatocellular carcinoma tumorigenesis by regulating the circ_0005785/miR-640/GSK3ß.

Paclitaxel (PTX) is an effective chemotherapeutic agent for cancer patients. It has been reported that circular RNA (circRNA) circ_0005785is involved in the progression of hepatocellular carcinoma (HCC). The purpose of this study is to explore the role and mechanism of circ_0005785 in the PTX resistance of HCC. Cell viability, proliferation, invasion, migration, apoptosis, and angiogenesis were detected using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT), colony formation, transwell, wound-healing, flow cytometry, and tube formation assay. Circ_0005785, microRNA-640 (miR-640), and Glycogen synthase kinase-3 beta (GSK3ß) levels were detected using real-time quantitative polymerase chain reaction. Protein levels of Proliferating cell nuclear antigen (PCNA), Bcl-2, and GSK3ß were measured using western blot assay. After being predicted using Circular RNA interactome or TargetScan, binding between miR-640 and circ_0005785 or GSK3ß was verified using dual-luciferase reporter and RNA Immunoprecipitation assay. PTX treatment could repress HCC cell viability, decrease circ_0005785 and GSK3ß expression, and increase the miR-640 level in HCC cell lines. Furthermore, circ_0005785 and GSK3ß were increased, and miR-640 was decreased in HCC tissues and cell lines. Moreover, circ_0005785 knockdown hindered proliferation, migration, invasion, angiogenesis, and boosted apoptosis in PTX-treated HCC cells in vitro. In addition, circ_0005785 silencing improved the PTX sensitivity of HCC in vivo. Mechanistically, circ_0005785 acted as a sponge of miR-640 to regulate GSK3ß expression. PTX restrained HCC tumorigenesis partly via regulating the circ_0005785/miR-640/GSK3ß axis, hinting at a promising therapeutic target for the HCC treatment.

Long-term outcomes of transarterial embolization with lipiodol-bleomycin emulsion plus polyvinyl alcohol particles versus the particles alone for large symptomatic focal nodular hyperplasia: a propensity score-matched analysis.

OBJECTIVES: To compare the efficacy of transarterial embolization (TAE) with polyvinyl alcohol (PVA) particles alone and lipiodol-bleomycin emulsion (LBE) plus PVA particles for patients with unresectable large symptomatic focal nodular hyperplasia (FNH). METHODS: We performed a retrospective analysis of patients who underwent TAE either with PVA particles alone (group A, n = 46) or LBE plus PVA particles (group B, n = 35) for large (≥ 7 cm) symptomatic FNH between January 2002 and February 2019. Propensity score matching (PSM) (1:1) was performed to adjust for potential baseline confounders. Technical success, adverse events (AEs), symptom relief, and changes in the lesion size after TAE were evaluated. Statistical analysis included Wilcoxon rank sum test and χ2 test. RESULTS: After PSM, no significant differences in baseline characteristics were found between the groups (31 in group A and 31 in group B, with a mean age of 31 years). Technical success was achieved in all patients (100%), without major AEs in both groups. Complete resolution of the abdominal symptoms was reported in 77.4% in group A and 100% in group B (p = 0.037) during a mean follow-up period of 72 months; complete resolution (CR) of the FNH rate was significantly higher in group B than in group A (93.6% vs. 67.7%; p = 0.019). CONCLUSION: Compared with the use PVA particles alone, TAE with LBE plus PVA particles in the treatment of patients with large symptomatic FNH had a significantly higher rates of CR of the FNH and complete relief of the symptoms. KEY POINTS: • Transarterial embolization (TAE) with lipiodol-bleomycin emulsion (LBE) plus PVA particles for the large symptomatic FNH yielded better results than with PVA particles alone, in terms of complete resolution of FNH lesions (93.6% vs 67.7%) and complete relief of the abdominal symptoms (100% vs 77.4%) during a mean follow-up period of 72 months (38-170 months). • No major complications were recorded in both groups, and no significant difference in the incidence of postembolization syndrome were observed between the two groups.

CAR-T cell therapy targeting B cell maturation antigen is effective for relapsed/refractory multiple myeloma, including cases with poor performance status.

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 × 106 CAR+ cells/kg), 17 patients (34.69%, 11 ECOG 0-2, 6 ECOG 3-4) developed cytokine release syndrome [grade 1-2: 14 patients (28.57%); grade 3: 3 patients (6.12%)]. The objective response rate (ORR) was 77%, with a complete response (CR) achieved in 47%. Ongoing response >12 months occurred in 15 patients, and was extended beyond 38 months in one patient. The median progression-free survival (PFS) and overall survival (OS) were 10 months (95% CI 5.3-14.7) and 29 months (95% CI 10.0-48.0), respectively. The PFS (12 months) and OS (18 months) rates were 41.64% and 62.76%, respectively. In patients with ECOG 0-2 and 3-4, ORR was 79.31% (23/29) and 75.0% (15/20) and PFS were 15 months (95% CI 5.4-24.6) and 4 months (95% CI 0-11.7), respectively. OS was not reached in ECOG 0-2 patients, but was 10.5 months (95% CI 0-22) in ECOG 3-4 patients. Single-cell sequencing indicated that treatment efficacy might be related to mTORC1 signaling. Thus, HDS269B therapy is safe and effective for RRMM patients, even those with ECOG 3-4.

The outcomes of interventional treatment for Budd-Chiari Syndrome complicated by inferior vena cava thrombosis: Systematic review and meta-analysis.

PURPOSE: The aim of this study was to perform a systematic review and meta-analysis to assess the safety and efficacy of interventional treatment for Budd-Chiari syndrome (BCS) complicated by Inferior Vena Cava thrombosis (IVCT) patients. METHODS: We evaluated the published studies on interventional treatment for BCS complicated by IVCT. Meta-analysis was used to calculate the combined effect size and their 95% confidence intervals (CI) based on random effect. The publication bias was assessed by Begg's test. RESULTS: Sixteen studies on interventional treatment for BCS complicated by IVCT patient were selected for meta-analysis, a total of 767 BCS complicated by IVCT patients were included. The combined effect size (95% CI) were 99% (98-100%) for the total successful rate of IVC recanalization, 15% (11-21%) for the rate of IVC restenosis after initial operation, 92.0% (86-97%) for the rate of clinical improvement, 76% (68-84%) for the rate of thrombus clearance and 0.00% (0-1%) for the incidence of pulmonary embolism (PE). Through subgroup meta-analysis about the rate of thrombus clearance, we got the pooled results (95% CI) of individualized treatment strategy (ITS) group and non-individualized treatment strategy (non-ITS) group, were 81% (71-92%) and 73% (63-83%), respectively. CONCLUSIONS: The interventional treatment for BCS complicated by IVCT patients is safe and effective with low incidence of PE, high thrombus clearance rate, high technically successful rate, good patency, and high clinical improvement rate. Moreover, subgroup analysis indicated that management based on the type and extent of the thrombus is proposed.

A meta-analysis of total knee arthroplasty following high tibial osteotomy versus primary total knee arthroplasty.

BACKGROUND: This study was performed to compare the clinical and radiographic outcomes of total knee arthroplasty (TKA) following high tibial osteotomy (HTO) versus primary TKA. METHODS: Relevant trials were identified via a search of Ovid, PubMed and the Cochrane Central Register of Controlled Trials from inception to 10 January 2019. A meta-analysis was performed to compare postoperative outcomes between revising HTO to TKA (RHTO) and primary TKA (PTKA) with respect to Knee Society Score (KSS), 10-year survival rate, operative time, flexion and extension angle, infection rate and radiographic results. RESULTS: Sixteen of 340 studies involving 103,552 adult patients (RHTO group, n = 3955; PTKA group, n = 99,597) were eligible for inclusion in the meta-analysis. Compared with primary TKA, revising HTO to TKA required longer operative time and had a higher infection rate (P < 0.05). The PTKA group had better flexion angle than the RHTO group (P < 0.05). There were no significant differences between the two groups in the KSS, extension angle, radiographic results and 10-year survival rate (P > 0.05). CONCLUSION: Patients who undergo conversion of HTO to TKA have similar 10-year survival rate, KSS, extension angle and radiographic results as patients who undergo primary TKA. However, conversion of HTO to TKA required longer operative time and had a higher infection rate than performing primary TKA. Moreover, conversion of HTO to TKA is associated with poorer flexion angle than primary TKA.

Pooled analysis of the reports of carfilzomib/ixazomib combinations for relapsed/refractory multiple myeloma.

We sought to evaluate the activity and safety of carfilzomib-/ixazomib-containing combinations for patients with relapsed/refractory multiple myeloma (RRMM). We searched published reports including carfilzomib-/ixazomib-containing combinations for RRMM. Finally, we identified 11 prospective studies covering 2845 relapsed/refractory patients. Carfilzomib- and ixazomib-containing combinations respectively resulted in an impressive overall response rate (ORR 77 vs. 64%, P = 0.14), very good partial response or better (≥ VGPR 48 vs. 21%, P = 0.001), complete response or better (≥ CR 14 vs. 7%, P = 0.23), and clinical benefit rate (CBR 84 vs. 59%, P = 0.0002). Subgroup analysis showed that the carfilzomib (CFZ) +lenalidomide (LEN) + dexamethasone (DEX) triplet regimen resulted into similar response outcomes to those from CFZ + DEX doublet regimen in ORR (77 vs. 78%, P = 0.91), ≥VGPR (50 vs. 53%, P = 0.84), and ≥ CR (13 vs. 12%, P = 0.96) analysis in these previously heavily pretreated population. And, there were no statistically significant differences between IXA + LEN + DEX triplet regimen and CFZ + LEN + DEX triplet regimen in ORR (85 vs. 78%, P = 0.55), ≥ VGPR (37 vs. 53%, P = 0.19), and ≥ CR (18 vs. 12%, P = 0.70) analysis. There were favorable trend towards proteasome inhibitors (PIs) + IMiDs + DEX in comparison with PIs + alkylating agent + Dex in ORR (79 vs 49%, P < 0.00001), ≥ VGPR analysis (36 vs. 16%, P = 0.008), and ≥ CR (16 vs. 3%, P < 0.00001). Compared with current standard chemotherapy, carfilzomib containing combinations clearly improved overall survival (HR, 0.79; P = 0.01), progression free survival (HR, 0.61; P = 0.0001). Carfilzomib-/ixazomib-containing combinations produced clinical benefit for patients with R/RMM. PIs + IMiDs + DEX triplet regimens could be good options for such relapsed/refractory patients.

Hepatitis C Virus Particle Assembly Involves Phosphorylation of NS5A by the c-Abl Tyrosine Kinase.

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).

[Pattern recognition of decorative papers with different visual characteristics using visible spectroscopy coupled with principal component analysis (PCA)].

As one of the most important decorative materials for the modern household products, decorative papers impregnated with melamine not only have better decorative performance, but also could greatly improve the surface properties of materials. However, the appearance quality (such as color-difference evaluation and control) of decorative papers, as an important index for the surface quality of decorative paper, has been a puzzle for manufacturers and consumers. Nowadays, human eye is used to discriminate whether there exist color difference in the factory, which is not only of low efficiency but also prone to bring subjective error. Thus, it is of great significance to find an effective method in order to realize the fast recognition and classification of the decorative papers. In the present study, the visible spectroscopy coupled with principal component analysis (PCA) was used for the pattern recognition of decorative papers with different visual characteristics to investigate the feasibility of visible spectroscopy to rapidly recognize the types of decorative papers. The results showed that the correlation between visible spectroscopy and visual characteristics (L*, a* and b*) was significant, and the correlation coefficients wereup to 0.85 and some was even more than 0. 99, which might suggest that the visible spectroscopy reflected some information about visual characteristics on the surface of decorative papers. When using the visible spectroscopy coupled with PCA to recognize the types of decorative papers, the accuracy reached 94%-100%, which might suggest that the visible spectroscopy was a very potential new method for the rapid, objective and accurate recognition of decorative papers with different visual characteristics.

Family-based analysis of INSR polymorphisms in Chinese PCOS.

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.

The predictive value of four traumatic hemorrhage scores for early massive blood transfusion in trauma patients in the pre-hospital setting.

OBJECTIVES: We aimed to explore the predictive value of four traumatic hemorrhage scores for early massive blood transfusion in trauma patients in the pre-hospital setting. METHODS: Trauma patients admitted to Shenzhen University General Hospital from July 2018 to December 2022 were included in this study. They were divided into the massive transfusion group and the non-massive transfusion group according to the blood transfusion volume within 24 h. Basic information about patients was collected. Glasgow Coma Scale (GCS), focused assessment with sonography for trauma (FAST), and injury severity score (ISS) were performed. The receiving operating characteristic (ROC) curve was used to compare the predictive value of four trauma transfusion scores for early massive blood transfusion in the pre-hospital setting. RESULTS: A total of 475 patients were enrolled, 43 received massive blood transfusions and 29 died within 24 h. The sensitivity and specificity of the four trauma hemorrhage scores in predicting the need for massive blood transfusions in trauma patients at their recommended cutoff points were all high. Among the four scores, the area under the ROC curve was larger for the assessment of blood consumption (ABC) score (0.864) and smaller for the trauma-induced coagulopathy clinical score (TICCS) score (0.795, p > 0.05). CONCLUSIONS: All four pre-hospital trauma hemorrhage scores have a high predictive value in assessing massive blood transfusion in trauma patients.

The "blownknee" patient's stress fracture of distal tibial component after unilateral TKA: A case report.

RATIONALE: Periprosthetic fractures (PPF) are rare complications of total knee arthroplasty (TKA). The most common PPF after TKA is supracondylar femoral fracture, which is a relatively rare complication that is usually associated with high-energy trauma, with a reported incidence ranging from 0.4 to 1.7% according to the AOANJRR. However, in TKA patients, it is rarer that the stress fracture around the tibial prosthesis occurs due to changes in the lower limb force line, increasing weight-bearing, and changes in walking gait. PATIENT CONCERNS: A 68-year-old woman visited our hospital with "both knees had aggravated pain and deformity for 8 years." TKA was performed first on the left knee and the patient was discharged within 1 week. Three months later, the patient complained of pain in the upper middle 1/3 part of the medial tibia for 2 weeks, which gradually worsened and affected weight-bearing. DIAGNOSES: Physical examination showed that the left knee joint presented varus deformity, and the right valgus deformity, which diagnosed as osteoarthritis of both knees and was so-called "blownknee". The disease was initially diagnosed as osteoarthritis of both knees on first admission and PPF of the tibia in second. INTERVENTIONS: Three operations were performed on this patient. The first was TKA of the left knee, the second was open reduction and internal fixation of the PPF of the tibia 3 months after the first operation, and the third was TKA of the right knee. OUTCOMES: Until now, the patient has had no recurrent PPF, and the fracture is healing from the last X-ray. LESSONS: Clinicians should be aware of the possibility of PPF after TKA, especially in such patients, the most preferred surgical treatment method was open reduction and internal fixation of fractures using locking plates, and if the PPF with loosened implants, Revision TKA, or megaprosthesis was the better choice.

Correlation between computed tomography-based body composition parameters and hepatic venous pressure gradient in patients with cirrhosis: a systematic review and meta-analysis.

PURPOSE: Computed tomography (CT)-based body composition parameters and the hepatic venous pressure gradient (HVPG) are key characteristics in patients with liver cirrhosis. The present study aims to explore the correlation between CT-based body composition parameters and HVPG, as well as the difference in HVPG between patients with and patients without sarcopenia. METHODS: A literature search for studies reporting the correlation between HVPG and CT-based body composition parameters published in English up to August 2023 in four databases, Embase, MEDLINE (via PubMed), Web of Science, and Cochrane Library, was conducted. The correlation coefficient between HVPG and CT-based body composition parameters was the primary outcome, and the difference in the HVPG value between the sarcopenia and non-sarcopenia groups was the secondary outcome. A meta-analysis was conducted using a random-effects models. The methodologic quality was assessed using the Quality Assessment of Diagnostic Studies instrument. RESULTS: A total of 652 articles were identified, of which nine studies (n = 1,569) met the eligibility criteria. Among them, seven studies reported the primary outcome via the muscle index, five via the skeletal muscle index (SMI), two via the psoas-muscle-related index (PRI), and three via two adipose tissue indexes. A total of five studies reported the secondary outcome: four via SMI and one via PRI. No evidence of a significant correlation was determined between the various body composition parameters and the HVPG value, either in the muscle index or the adipose tissue index. Higher HVPG values were observed in patients with sarcopenia than in patients without sarcopenia [pooled standardized mean difference (SMD): 0.628 (-0.350, 1.606), P < 0.001; I2 = 92.8%; P < 0.001] when an Asian sarcopenia definition was adopted. In contrast, when a Western cut-off value was applied, the HVPG value was higher in patients without sarcopenia than in patients with sarcopenia [pooled SMD: -0.201 (-0.366, -0.037), P = 0.016; I2 = 0.00%; P = 0.785]. CONCLUSION: No sufficient evidence regarding a correlation between the CT-based body composition and HVPG value was discovered. The difference in the HVPG value between the sarcopenia and non-sarcopenia groups was likely dependent on the sarcopenic cut-off value.

A 5-Year Follow-up Clinical Study of the B-cell Maturation Antigen Chimeric Antigen Receptor T-cell Therapy HDS269B in Patients with Relapsed or Refractory Multiple Myeloma.

PURPOSE: This study aimed to report the 5-year clinical outcomes of anti-B-cell maturation antigen chimeric antigen receptor (CAR) T-cell (HDS269B) therapy in patients with relapsed/refractory multiple myeloma (RRMM), including those with poor performance status [Eastern Cooperative Oncology Group (ECOG) scores 3 to 4], and to identify factors influencing long-term outcomes. PATIENTS AND METHODS: Forty-nine patients with RRMM enrolled from 2016 to 2020 received HDS269B (9 × 106 cells/kg) after receiving a conditioning chemotherapy consisting of cyclophosphamide and fludarabine. The overall response, long-term outcomes, and safety were assessed, as were their associations with clinical and disease characteristics. RESULTS: With a median follow-up of 59.0 months, the overall response rate was 77.55%. The median progression-free survival (PFS) and overall survival (OS) were 9.5 months [95% confidence interval (CI), 5.01-13.99] and 20.0 months (95% CI, 11.26-28.74), respectively. The 5-year PFS and OS rates were 21.3% (95% CI, 12.3%-36.7%) and 34.1% (95% CI, 22.7%-51.3%), respectively. Patients with ECOG 0 to 2 had marked longer survival, with a median PFS of 11.0 months and a median OS of 41.8 months. Early minimal residual disease negativity, higher and persistent CAR T-cell expansion, and the absence of extramedullary disease were associated with better survival outcomes. No new CAR T-cell therapy-associated toxicities were observed. Importantly, ECOG scores 0 to 2, prior therapy lines <4, and CAR T-cell persistence at ≥6 months were independently associated with longer OS. CONCLUSIONS: HDS269B is effective and safe, especially for patients with ECOG scores 0 to 2. Early CAR T-cell intervention may improve prognosis in patients with RRMM.

Sequencing of systemic therapy in unresectable hepatocellular carcinoma: A systematic review and Bayesian network meta-analysis of randomized clinical trials.

PURPOSE: For patients with advanced or unresectable hepatocellular carcinoma (HCC), safe and effective therapies are urgently needed to improve their long-term prognosis. Although the guidelines recommend first-line treatments such as sorafenib, lenvatinib, and atezolizumab in combination with bevacizumab (T+A) and second-line treatments such as regorafenib, the efficacy comparison between drugs is lacking, that is, a treatment is not recommended as the optimal or alternative choice for a specific patient population. Therefore, we will conduct a high-quality network meta-analysis based on Phase III randomized controlled trials (RCTs) to systematically evaluate and compare overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and serious adverse events (SAE) of different treatment protocols in the context of first-line and second-line therapies, which are critical for clinical decision making and prognostic improvement in advanced HCC patients. METHODS: The studies of interest were Phase III RCTs evaluating the efficacy or safety of first- or second-line therapies in patients with unresectable or advanced HCC. Literature published in English from the four databases of PubMed, Embase, Cochrane Library, and Web of Science was comprehensively searched from the inception to May 23, 2022. Outcomes of interest included OS, PFS, ORR, and SAE. A league table was developed to show the results of the comparison between different treatments. A histogram of cumulative probability was drawn to discuss the ranking probability of treatments based on different outcomes. The effectiveness and safety of various treatments were comprehensively considered and the two-dimensional diagram was plotted to guide clinical practice. The Gemtc package in R Studio was used for network meta-analysis in a Bayesian framework. RESULTS: The results showed that HAIC-FO was superior to T+A regimen, regardless of OS, PFS or ORR. TACE combined with lenvatinib performed better than T+A in PFS, and ORR. In addition to the T+A regimen, Sintilimab combined with IBI305 and camrelizumab combined with apatinib were also associated with longer OS, PFS, and ORR, and their SAE incidence was not higher than that of T+A, especially for camrelizumab combined with apatinib, its safety was better than that of T+A regimen. There were no new treatments or combinations that were more effective than regorafenib. It was important to note that for PFS, the efficacy of apatinib and cabozantinib was not statistically different from that of regorafenib, so these two treatments could be used as alternative treatment options in cases where regorafenib was not tolerated or treatment failed. CONCLUSIONS: We conducted a network meta-analysis to evaluate the efficacy and safety of multiple treatment modalities by integrating the results of direct and indirect comparisons. This study included high-quality multicenter Phase III RCTs, collated and summarized all treatments involved in advanced or unresectable HCC in first-line and second-line settings, and compared with T+A and regorafenib, respectively, and ranked based on efficacy and safety to support clinical decision making.

Inactivation of JNK signalling results in polarity loss and cell senescence of Sertoli cell.

As major somatic cells in the testis, Sertoli cell development is precisely regulated by numerous factors, and aberrant development of these cells is associated with male reproductive diseases. JNK signalling is evolutionarily conserved and involved in multiple critical biological processes. Here, we found that the double knockout of Jnk1 and Jnk2 resulted in aberrant localisation of Sertoli cells at early developmental stages, with most Sertoli cells being lost at later stages. Further studies revealed that the inactivation of JNK signalling caused polarity loss in Sertoli cells. In vitro-cultured Jnk1/2-DKO Sertoli cells exhibited a senescence-associated phenotype. Mechanistic studies demonstrate that JNK signalling is likely involved in establishing Sertoli cell polarity by regulating the expression of TGF-ß2, mediated by c-Jun. The senescence of Sertoli cells in JNKs-deficient mice is caused by aberrant proteolysis of P27KIP1, mediated by c-Myc. This study demonstrates the role of JNK signalling in Sertoli cell development and functional maintenance, which may also represent an aetiology of male infertility in humans.

Alteration in abundance and compartmentalization of inflammation-related miRNAs in plasma after intracerebral hemorrhage.

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.

Infusion of HLA-mismatched peripheral blood stem cells improves the outcome of chemotherapy for acute myeloid leukemia in elderly patients.

Treatment outcome of acute myeloid leukemia (AML) in elderly patients remains unsatisfactory. It has been shown that the infusion of granulocyte colony-stimulating factor-mobilized donor peripheral blood stem cells (G-PBSCs) can enhance graft-versus-leukemia effects and speed hematopoietic recovery. Fifty-eight AML patients aged 60-88 years were randomly assigned to receive induction chemotherapy with cytarabine and mitoxantrone (control group; n = 28) or it plus human leukocyte antigen-mismatched G-PBSCs (G-PBSC group; n = 30). Patients who achieved complete remission received another 2 cycles of postremission therapy with intermediate-dose cytarabine or it plus G-PBSCs. The complete remission rate was significantly higher in the G-PBSC group than in the control group (80.0% vs 42.8%; P = .006). The median recovery times of neutrophils and platelets were 11 days and 14.5 days, respectively, in the G-PBSC group and 16 days and 20 days, respectively, in the control group after chemotherapy. The 2-year probability of disease-free survival was significantly higher in the G-PBSC group than in the control group (38.9% vs 10.0%; P = .01). No graft-versus-host disease was observed in any patient. Persistent donor microchimerism was successfully detected in all of the 4 female patients. These results indicate that G-PBSCs in combination with conventional chemotherapy may provide a promising treatment method for AML in elderly patients.