Tissue-Matched IgH Gene Rearrangement of Circulating Tumor DNA Shows Significant Value in Predicting the Progression of Diffuse Large B Cell Lymphoma.

BACKGROUND: Evidence has demonstrated that monitoring of the variable, diversity, and joining gene segments (VDJ) rearrangement of the immunoglobulin (Ig) genes in the circulating tumor DNA (ctDNA) is of value in predicting the outcomes of diffuse large B cell lymphoma (DLBCL). In this study, we investigated the role of VDJ rearrangement proportion in ctDNA for predicting DLBCL progression. METHODS: Patients diagnosed with newly diagnosed DLBCL were included in this study. The VDJ sequences of IgH were detected using next-generation sequencing (NGS) in formalin-fixed paraffin-embedded tissue and/or peripheral blood. The clonotype of the highest proportion in the peripheral blood was defined as the "dominant circulating clonotype," whilst the clonotype of the highest proportion in matched tissue that is detected in peripheral blood was defined as the "dominant tissue-matched clonotype." The decision tree, a machine learning-based methodology, was used to establish a progression-predicting model through a combination of "dominant tissue-matched clonotype" proportion or "dominant circulating clonotype" proportion, and the clinicopathological information, including age, sex, cell of origin, stage, international prognostic index, lactate dehydrogenase, number of extranodal involvements and ß2-microglobulin. RESULTS: A total of 55 patients with eligible sequencing data were used for prognosis analysis, among which 36 patients had matched tissue samples. The concordance rate of "dominant circulating clonotype" and "dominant tissue-matched clonotype" was 19.44% (7/36). The decision tree model showed that the combination of extranodal involvement event and "dominant circulating clonotype" proportion (≥37%) had a clinical value in predicting the prognosis of DLBCL following combined chemotherapy (sensitivity, 0.63; specificity, 0.81; positive prediction value (PPV), 0.59; negative prediction value, 0.83; kappa value, 0.42). Noticeably, the combination of the "dominant tissue-matched clonotype" and extranodal involvement event showed a higher value in predicting the progression (sensitivity, 0.85; specificity, 0.78; PPV, 0.69; kappa value, 0.64). CONCLUSION: IgH proportion detected in the ctDNA samples traced from tissue samples has a high clinical value in predicting the progression of DLBCL.

Clinical features, etiology, and prognosis of hand knob stroke: a case series.

BACKGROUND: Hand knob stroke is a rare clinical disorder frequently misdiagnosed as peripheral neuropathy. The purpose of this study is to recognize this particular type of stroke by analyzing clinical features, etiology, and prognosis. METHODS: We enrolled 19 patients with acute hand knob stroke in the Department of Neurology of the Beijing Geriatric Hospital from January 2018 to January 2022, and the clinical and imaging data of the patients during hospitalization and follow-up were collected and summarized. RESULTS: Acute hand knob stroke accounted for 0.9% of all acute stroke, and ischemic stroke (17 cases, 89.5%) was more than hemorrhagic stroke (2 cases, 10.5%). All patients presented sudden contralateral hand paresis, 12 (63.2%) of them had only isolated hand paralysis, and the location of the lesion corresponded to different finger weakness. The cause of hand knob hemorrhage was hypertension, while the causes of hand knob infarction were mainly small-vessel occlusion (SVO) (35.3%) and large-artery atherosclerosis (LAA) (35.3%), and the rare causes include carotid artery dissection and carotid body tumor. After a median follow-up 13.5 months, the prognosis of 94.7% patients was good, and one patient (5.3%) had recurrent stroke. CONCLUSIONS: Hand knob stroke is a rare stroke with a good prognosis and a low stroke recurrence rate. Ischemic stroke is the predominant type and the main clinical manifestation is hand paresis. The cause of hand knob hemorrhage is hypertensive, while SVO and LAA are the main causes of hand knob infarction, but there are some rare etiologies.

Differences in the therapeutic effects of high-intensity focused ultrasound (HIFU) ablation on uterine fibroids with different shear wave velocity (SWV): a study of histopathological characteristics.

OBJECTIVE: To explore correlations between the therapeutic effect of high intensity focused ultrasound (HIFU) and histopathological characteristics of uterine fibroids with different Shear Wave Velocity (SWV) values. METHODS: A retrospective study was conducted on 36 women (43 fibroids) who had undergone high intensity focused ultrasound (HIFU) uterine fibroids ablation between January 2019 and January 2020. Preoperative fibroids tissue sections were obtained for histopathological examination. The pathological sections were stained with Masson-trichrome, and were observed and imaged under a Low-power microscope (4 × 10), while the smooth muscle cell (SMC) and collagen fiber content were semi-quantitatively measured. Preoperative fibroid SWV was measured using the Virtual Touch tissue quantification (VTQ) technique. Within one month after HIFU ablation, all patients had undergone a pelvic cavity MRI examination, which measured the size, volume, and non-perfused volume (NPV) of the fibroids. The formula: the ablation rate = NPV/target fibroid volume × 100% was used to calculate the ablation rate of the uterine fibroids. Correlation analysis of SWV values, HIFU ablation rate, along with the smooth muscle cell (SMC) and collagen fiber content, were conducted using the Spearman's correlation test. RESULTS: The collagen fiber and SMC content of the preoperative fibroids were 32.09 ± 15.90%/view and 37.61 ± 15.32%/view, respectively. Preoperative fibroid SWV value was 3.56 ± 0.71 m/s. Preoperative fibroid SWV was negatively correlated with SMC content (r = -0.445, p = 0.003), but positively correlated with collagen fiber content (r = 0.454, p = 0.002). The ablation rate was negatively correlated with collagen fiber content (r = -0.377, p = 0.013), but positively correlated with SMC content (r = 0.402, p = 0.007). CONCLUSION: Differences in histopathological characteristics may be important factors that induce differences in the therapeutic effects of HIFU ablation on uterine fibroids with different SWV values.

The value of acoustic radiation force impulse imaging in preoperative prediction for efficacy of high-Intensity focused ultrasound uterine fibroids ablation.

Objective: To investigate the application value of acoustic radiation force impulse imaging in preoperative prediction for efficacy of High-Intensity Focused Ultrasound uterine fibroids ablationMethods: A prospective study was conducted on 32 women (41 fibroids) undergoing HIFU uterine fibroids ablation between January 2019 and September 2019. The virtual touch tissue quantification (VTQ) technique was used for the preoperative determination of uterine fibroids shear wave velocity (SWV). The stiffness of the preoperative uterine fibroids was graded on a virtual touch tissue image (VTI). All uterine fibroids were ablated with a single point ablation acoustic power of 400 W. All patients underwent pelvic cavity MRI examination for the measurement of the size, volume and non-perfused volume (NPV) of fibroids within the first month after HIFU ablation. The ablation rate of uterine fibroids was calculated according to the formula: ablation rate = NPV × 100/target fibroid volume. The patients were divided into two groups based on the postoperative ablation rate: ≥70% ablation rate group, and＜70% ablation rate group. The preoperative SWV and VTI grade of uterine fibroids were compared between the two groups. The correlation of preoperative uterine fibroids' SWV and VTI grade with HIFU ablation rate were analyzed using the Spearman's correlation coefficient. The optimal cutoff points in preoperative uterine fibroids SWV of 70% ablation rate were determined by receiver operating curve (ROC) analysis.Results: A total of 30 patients (73.17%, 30/41) showed ablation rate ≥70%, with preoperative uterine fibroids' SWV values of (3.42 ± 0.71) m/s. Of these, 24 patients (80%, 24/30) had VTI grades II-III. On the other hand, 26.83% (11/41) showed ablation rate <70%, with preoperative uterine fibroids' SWV values of (4.02 ± 0.69) m/s; of these, 63.6% (7/11) had VTI grade IV. The SWV values and VTI grades of preoperative uterine fibroids were significantly different in the two groups (p < 0.05). Interestingly, postoperative ablation rate was negatively correlated with preoperative uterine fibroids' SWV values (r= -0.536, p = 0.0003) and VTI grades (r= -0.511, p = 0.001). The area under the ROC curve of preoperative uterine fibroids' SWV values with ablation rate <70% was 0.75 at a cutoff value of 3.915 m/s (p < 0.05). Specificity was 72.7% and sensitivity was 80.1%; the positive predictive value was 72.7%, and the negative predictive value was 80%.Conclusion: ARFI technique is an effective and feasible noninvasive ultrasound technique for the preoperative prediction of the efficacy of HIFU uterine fibroids ablation.

The fused in sarcoma protein forms cytoplasmic aggregates in motor neurons derived from integration-free induced pluripotent stem cells generated from a patient with familial amyotrophic lateral sclerosis carrying the FUS-P525L mutation.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that primarily affects motor neurons (MNs) and has no effective treatment. Mutations in the fused in sarcoma (FUS) gene and abnormal aggregation of FUS protein have been reported in ALS. However, the mechanisms involved in ALS are poorly understood. Clinical drug trails have failed due to a lack of appropriate disease models, including a lack of access to MNs from ALS patients. Induced pluripotent stem (iPS) cells derived from patients with ALS provide an indispensable resource for in vitro mechanistic studies and for future patient-specific cell-based therapies. Previous reports demonstrated that viral-based ALS-iPS cells generated from fibroblasts harvested from Caucasian populations are ideal for basic research; however, ALS-iPS cells are precluded from cell-based therapeutic applications because of the risks associated with the integration of viral sequences into the genome and inconvenience associated with dermal biopsies. To establish a model for use in clinical applications, using episomal vectors, we generated an integration-free iPS cell line from peripheral blood mononuclear cells (PBMCs) harvested from a familial ALS (FALS) patient carrying the FUS-P525L mutation and a healthy control. Furthermore, we successfully differentiated ALS patient-specific iPS cells into MNs and subsequently detected cytoplasmic mislocalization and formation of FUS protein aggregates in MNs due to the FUS-P525L mutation. Our findings offer a cell-based disease model for use in further elucidating ALS pathogenesis and provide a tool for exploring gene repair coupled with cell replacement therapy.

[Generation of induced pluripotent stem cells from amyotrophic lateral sclerosis patientcarrying SOD1-V14M mutation].

OBJECTIVE: To generate familial ALS patient specific induced pluripotent stem (iPS) cell lines and motor neurons and provide a cell-based disease model for amyotrophic lateral sclerosis (ALS) in Han Chinese. METHODS: iPS cells were derived from familial ALS patient by introducing 4 transcription factors OCT3/4, SOX2, KLF4 and c-MYC into fibroblast cells by retroviruses. Karyotypic analysis, immunofluorescence staining and quantitative reverse transcription-polymerase chain reaction (RT-PCR) were used to identify the pluripotency of these iPS cell lines. In addition, motor neurons were derived from these iPS cells by inhibiting SMAD pathway. RESULTS: IPS cell lines were established from ALS patient carrying SOD1-V14M mutation. They had pluripotency and were similar to human ES cells. Furthermore, motor neurons were successfully induced from these iPS cells. CONCLUSION: SOD1-V14M mutation does not affect the reprogramming of fibroblast cells and pluripotency of iPS cells, nor does it prevent differentiation of motor neurons. Furthermore, the above cell-based disease model can recapitulate key aspects of ALS pathogenesis so that it provides an indispensible resource for further elucidating ALS disease pathogenesis and screening appropriate drug candidates in Han Chinese.

[Clinical effects of treatment of sIUGR in MCDA pregnancies by fetoscopic laser photocoagulation].

OBJECTIVE: To study the outcome of fetoscopic laser photocoagulation (laser) in the management of monochorionic diamniotic twin (MCDA) pregnancies complicated with selective intra-uterine growth restriction (sIUGR). METHODS: Retrospective analysis of 5 MCDA twin pregnancies with sIUGR treated by laser. RESULTS: All 5 cases were sIUGR type II. In all 5 cases, the growth restriction was associated with oligohydamnios, and the umbilical cord had marginal insertion to the placenta. Abnormal Doppler flow pattern of the ductus venosus was present in 3 cases. Indication for laser therapy was beause of high risk of deterioration and fetal demise of the growth restricted fetus. In all cases, fetal reduction as an alternative was discussed and was refused. The median gestation at laser was 19 weeks. The procedure was successful in all cases, with complete seperation of the vascular anastomoses. There was no case of immediate postoperative complications. Fetal karyotype was normal in all cases. Fetal death of the small twin occurs in all cases within two weeks after surgery. Follow up studies of the surviving twin in all cases showed normal fetal growth, amniotic fluid volume, and middle cerebral artery peak systolic velocity. All cases resulted in preterm labor, with a median gestational age of 32 weeks (30(+3) weeks to 34 weeks ), and a median birth weight of 1 540 g (1 100-2 080 g); the postoperative fetal survival rate was 5/10, with at least one child survival rate of 5/5. There was no neonatal complication in the survival twins. Postnatal pathological examination of the placenta confirmed MCDA twin in all cases. CONCLUSIONS: Laser treatment of MCDA twin complicated with sIUGR is effective. It protects the normal fetus even when the growth restricted twin died. However, the intention to give a small chance of survival to the growth restricted fetus by avoiding fetal redution procedure was not successful. All of the sIUGR fetuses died due to placental insufficicent. This fact is important during the pre-treatment counselling to avoid unrealistic expectation.

The Value of Transanal Normal Saline Infusion-Assisted Multipath Ultrasonography in the Diagnosis of T1/T2 Rectal Cancer.

ABSTRACT: This study aims to assess the application value of transanal normal saline infusion-assisted multipath ultrasonography (TNSI-MU) in the diagnosis of T1/T2 rectal cancer (RC). All patients first received single-path 360-degree transrectal ultrasonography and then received 360-degree transrectal ultrasonography, transabdominal ultrasonography, or transvaginal ultrasonography after TNSI to determine the T stage. With surgical pathology as the criterion standard, the detection rates of T1/T2 RC lesions and the T-staging results of single-path 360-degree transrectal ultrasonography, TNSI-MU, and contrast-enhanced magnetic resonance imaging (MRI) were compared and analyzed. T1/T2 RC was surgically and pathologically confirmed in 52 patients. Single-path 360-degree transrectal ultrasonography had a lesion detection rate of 57.69% (30/52) and a T-staging accuracy of 80.0% (24/30), the sensitivity was 57.69%, and the specificity was 88.46%. Transanal normal saline infusion-assisted multipath ultrasonography had a lesion detection rate of 100%, and its T-staging accuracy was 84.62% (44/52), the sensitivity was 100%, and the specificity was 88.61%. Transanal normal saline infusion-assisted multipath ultrasonography had a significantly higher detection rate of T1/T2 RC lesions than single-path 360-degree transrectal ultrasonography ( P < 0.001), but the 2 methods had similar T-staging accuracy for T1/T2 RC (χ 2 = 0.286, P = 0.593). Contrast-enhanced MRI had a lesion detection rate of 100% and a T-staging accuracy of 40.38% (21/52), the sensitivity was 98.07%, and the specificity was 61.54%. Transanal normal saline infusion-assisted multipath ultrasonography had significantly higher diagnostic accuracy than contrast-enhanced MRI for T staging of T1/T2 RC ( P < 0.001), and the diagnostic results of the 2 methods were not consistent (κ = 0.151). Transanal normal saline infusion-assisted multipath ultrasonography outperformed single-path 360-degree transrectal ultrasonography in the detection rate of T1/T2 RC lesions and contrast-enhanced MRI in the staging accuracy for T1/T2 RC.

Single-cell transcriptome sequencing provides insight into multiple chemotherapy resistance in a patient with refractory DLBCL: a case report.

Relapsed and refractory diffuse large B-cell lymphoma (DLBCL) is associated with poor prognosis. As such, a comprehensive analysis of intratumoral components, intratumoral heterogeneity, and the immune microenvironment is essential to elucidate the mechanisms driving the progression of DLBCL and to develop new therapeutics. Here, we used single-cell transcriptome sequencing and conventional bulk next-generation sequencing (NGS) to understand the composite tumor landscape of a single patient who had experienced multiple tumor recurrences following several chemotherapy treatments. NGS revealed several key somatic mutations that are known to contribute to drug resistance. Based on gene expression profiles at the single-cell level, we identified four clusters of malignant B cells with distinct transcriptional signatures, showing high intra-tumoral heterogeneity. Among them, heterogeneity was reflected in activating several key pathways, human leukocyte antigen (HLA)-related molecules' expression, and key oncogenes, which may lead to multi-drug resistance. In addition, FOXP3+ regulatory CD4+ T cells and exhausted cytotoxic CD8+ T cells were identified, accounted for a significant proportion, and showed highly immunosuppressive properties. Finally, cell communication analysis indicated complex interactions between malignant B cells and T cells. In conclusion, this case report demonstrates the value of single-cell RNA sequencing for visualizing the tumor microenvironment and identifying potential therapeutic targets in a patient with treatment-refractory DLBCL. The combination of NGS and single-cell RNA sequencing may facilitate clinical decision-making and drug selection in challenging DLBCL cases.

Sintilimab (anti-PD-1 antibody) plus chidamide (histone deacetylase inhibitor) in relapsed or refractory extranodal natural killer T-cell lymphoma (SCENT): a phase Ib/II study.

Anti-PD-1 antibodies are a favorable treatment for relapsed or refractory extranodal natural killer T cell lymphoma (RR-ENKTL), however, the complete response (CR) rate and the duration of response (DOR) need to be improved. This phase 1b/2 study investigated the safety and efficacy of sintilimab, a fully human anti-PD-1 antibody, plus chidamide, an oral subtype-selective histone deacetylase inhibitor in 38 patients with RR-ENKTL. Expected objective response rate (ORR) of combination treatment was 80%. Patients received escalating doses of chidamide, administered concomitantly with fixed-dose sintilimab in 21-days cycles up to 12 months. No dose-limiting events were observed, RP2D of chidamide was 30 mg twice a week. Twenty-nine patients were enrolled in phase 2. In the intention-to-treat population (n = 37), overall response rate was 59.5% with a complete remission rate of 48.6%. The median DOR, progression-free survival (PFS), and overall survival (OS) were 25.3, 23.2, and 32.9 months, respectively. The most common grade 3 or higher treatment-emergent adverse events (AEs) were neutropenia (28.9%) and thrombocytopenia (10.5%), immune-related AEs were reported in 18 (47.3%) patients. Exploratory biomarker assessment suggested that a combination of dynamic plasma ctDNA and EBV-DNA played a vital prognostic role. STAT3 mutation shows an unfavorable prognosis. Although outcome of anticipate ORR was not achieved, sintilimab plus chidamide was shown to have a manageable safety profile and yielded encouraging CR rate and DOR in RR-ENKTL for the first time. It is a promising therapeutic option for this population.

Maternal body fluid lncRNAs serve as biomarkers to diagnose ventricular septal defect: from amniotic fluid to plasma.

Background: Maternal body fluids contain abundant cell-free fetal RNAs which have the potential to serve as indicators of fetal development and pathophysiological conditions. In this context, this study aimed to explore the potential diagnostic value of maternal circulating long non-coding RNAs (lncRNAs) in ventricular septal defect (VSD). Methods: The potential of lncRNAs as non-invasive prenatal biomarkers for VSD was evaluated using quantitative polymerase chain reaction (qPCR) and receiver operating characteristic (ROC) curve analysis. The biological processes and regulatory network of these lncRNAs were elucidated through bioinformatics analysis. Results: Three lncRNAs (LINC00598, LINC01551, and GATA3-AS1) were found to be consistent in both maternal plasma and amniotic fluid. These lncRNAs exhibited strong diagnostic performance for VSD, with AUC values of 0.852, 0.957, and 0.864, respectively. The bioinformatics analysis revealed the involvement of these lncRNAs in heart morphogenesis, actin cytoskeleton organization, cell cycle regulation, and protein binding through a competitive endogenous RNA (ceRNA) network at the post-transcriptional level. Conclusion: The cell-free lncRNAs present in the amniotic fluid have the potential to be released into the maternal circulation, making them promising candidates for investigating epigenetic regulation in VSD.

Novel-fosfamide monotherapy or in combination with doxorubicin versus doxorubicin alone in patients with advanced soft tissue sarcoma: A pooled analysis of randomized clinical trials.

BACKGROUND: Novel-fosfamides (NFOs) belong to active metabolites of ifosfamide that bypass the generation of toxic byproducts. In this analysis, we aimed to comprehensively assess the benefits and risks of NFO monotherapy or in combination with doxorubicin (DOX) versus single-drug DOX in previously untreated patients with advanced soft-tissue sarcoma (ASTS). METHODS: Online PubMed, Web of Science, Embase, and Cochrane CENTRAL databases were systematically searched on April 26, 2022. Objective response rate and disease control rate were primary outcomes. Overall survival (OS), progression-free survival (PFS), and grade ≥ 3 treatment-related adverse events were secondary outcomes. RESULTS: In all, 3 randomized clinical trials with a total of 1207 ASTS patients were eligible. DOX plus NFO combination therapy showed higher risk ratios of objective response rate (1.50, 95% CI 1.20-1.68, P = .0003) and disease control rate (1.15, 95% CI 1.05-1.27, P = .0030) compared with DOX monotherapy. Nevertheless, NFO-based monotherapy and combination therapy were found no improvements on OS (hazard ratio 0.93, 95% CI 0.52-1.65, P = .8050) and PFS (hazard ratio 0.88, 95% CI 0.54-1.43, P = .6088) against DOX. More incidences of grade 3 or worse anemia, thrombocytopenia, stomatitis, diarrhea, constipation, and febrile neutropenia were observed in NFO-based treatments. CONCLUSION: Adding NFO to DOX as first-line therapy improved the responses in ASTS patients but did not prolong OS and PFS. Grade 3 or worse treatment-related adverse events should be treated with caution during the NFO-based therapies.

Dysregulation of the circ_0087502/miR-1179/TGFBR2 pathway supports gemcitabine resistance in pancreatic cancer.

BACKGROUND: Circular RNAs (circRNAs) are a cohort of non-coding RNAs generated by back-splicing events. Accumulating evidence supports the crucial role of circRNAs in human tumorigenesis, metastasis, and chemoresistance. However, the role and mechanism of circRNA circ_0087502 in pancreatic cancer are yet unknown. METHODS: The expression and function of circ_0087502 in pancreatic cancer were investigated using qRT-PCR and cell experiments. The predicted binding between circ_0087502 and microRNA-1179 (miR-1179), and between miR-1179 and TGFBR2, were examined using reporter assays. RESULTS: Pancreatic cancer tissues and cell lines were discovered to express circ_0087502 at higher levels. Patients with pancreatic cancer who express circ_0087502 at high levels have a worse prognosis. In addition, circ_0087502 knockdown reduced the proliferation, migration, and invasion of pancreatic cancer cells and made them more sensitive to gemcitabine treatment. We found that circ_0087502 worked as a sponge for miR-1179, allowing miR-1179 to bind to the critical oncogene TGFBR2 in its 3'-untranslated region (3'-UTR). Pancreatic cancer cells were highly resistant to gemcitabine and had increased proliferation, migration, and invasion when miR-1179 was inhibited or overexpressed. CONCLUSION: These results confirm that circ_0087502 activates the miR-1179/TGFBR2 axis to promote gemcitabine resistance in pancreatic cancer. Thus, our data might lay the groundwork for developing novel therapeutic strategies targeting circ_0087502 in pancreatic cancer patients.

Irisin attenuates fine particulate matter induced acute lung injury by regulating Nod2/NF-κB signaling pathway.

Air pollution consisting of fine particulate matter (PM2.5) can induce or aggravate pulmonary inflammatory injury. Irisin has been shown to inhibit inflammation and help to protect against acute kidney, lung or brain injury. However, the role of irisin in lung inflammation after exposure to PM2.5 remains unclear. The aim of this study was to investigate the effect and molecular mechanism of irisin supplementation on in vitro and in vivo models of PM2.5-induced acute lung injury（ALI). C57BL/6 mice and alveolar macrophage cell line (MH-S) were treated with PM2.5. Histopathological examination and FNDC5/ irisin immunofluorescence staining was performed on lung tissue sections. MH-S cell viability was determined by CCK-8 assay. The levels of Nod2, NF-κB p65 and NLRP3 were detected by qRT-PCR and western blotting. The levels of cytokines (IL-1ß, IL-18 and TNF-α) were detected by ELISA. PM2.5 exposure induced increased secretion of pro-inflammatory factors and activation of Nod2, NF-κB p65 and NLRP3 as well as endogenous levels of irisin. In vivo and in vitro inflammation was alleviated by irisin supplementation. Irisin significantly decreased IL-1ß, IL-18, and TNF-α production at both mRNA and protein level. Expression levels of Nod2, NF-κB p65, and NLRP3 were all significantly affected by irisin. In vivo the degree of pulmonary injury and inflammatory infiltration was weakened after irisin administration. In vitro, irisin could inhibit the activation of the NLRP3 inflammasome for a sustained period of 24 h, and its inhibitory ability was gradually enhanced. In conclusion, our findings indicate that irisin can modulate the inflammatory injury of lung tissue caused by PM2.5 through the Nod2/NF-κB signaling pathway, suggesting that irisin can be a candidate for the therapeutic or preventive intervention in acute lung inflammation.

[Fetoscopic guided laser occlusion for twin-to-twin transfusion syndrome in 33 cases].

OBJECTIVE: To evaluate the clinical effect of fetoscopic laser occlusion of chorioangiopagous vessels (FLOC) for monochorionic diamniotic twins (MCDA) pregnancies complicated with twin-to-twin transfusion syndrome(TTTS). METHODS: The clinical data of 33 consecutive cases of TTTS from Mainland China, who had FLOC in the Department of Obstetrics and Gynaecology of Prince of Wales Hospital (The Chinese University of Hong Kong) from November 2003 to December 2010, were reviewed and analyzed for peri-operative complications, perinatal outcomes and fetal survival rate. Clinical stage of TTTS was according to the Quintero staging system. RESULTS: (1) Pregnancy characteristics: the mean maternal age was 30; the median gestational age at FLOC was 23(+4) weeks; according to the Quintero staging system, 3 cases were Quintero staging I, 14 cases were Quintero staging II, 7 cases were Quintero staging III and 9 cases were Quintero staging IV. For the 3 stage I cases, FLOC was performed for severe maternal symptoms of polyhyramnios or severe fetal cardiac dysfunction. (2) COMPLICATIONS: intraoperative complications occurred in 5 patients including four uterine bleedings at the puncture site, one placental vascular anastomosis bleeding. Postoperative complications occurred in 6 patients including 2 abortions and 1 intrauterine death within one week after operation, 2 abortions and 1 amniotic band syndrome occurred from two to four weeks after operation. (3) Perinatal outcome and fetal survival rate: the median interval of 33 patients between FLOC and delivery was 9(+4) weeks; the median gestational age at delivery was 31(+6) weeks; the gestation at delivery was less than 24 weeks in 6% (2/33), 24 to 28 weeks in 21% (7/33), 28 to 32 weeks in 18% (6/33), 32 to 37 weeks in 55% (18/33). The mean birth weight of the donor was 1600 g (350 - 2520 g); the mean birth weight of the recipiert was 1930 g (400 - 3040 g). The overall survival rate, the double infant survival rate, the single survival rate and survival rate for at least one twin was 59% (39/66), 52% (17/33), 15% (5/33) and 67% (22/33), respectively. The overall survival rate dropped from 61% (17/28) in Quintero staging II to 9/18 in Quintero staging IV. CONCLUSIONS: FLOC for MCDA complicated with TTTS is associated with an overall survival of about 60%. Major complications are rare. The outcome is not only related to Quintero staging but also the close monitoring and timely termination of pregnancy.

A Bayesian network analysis of immunotherapy and taxane chemotherapy as second- or later-line treatments in non-small cell lung cancer.

BACKGROUND: Taxane chemotherapy represents the standard of care in the second-line setting for non-small cell lung cancer (NSCLC) patients, but immunotherapy agents pose great challenges. Whether immunotherapy/chemotherapy alone or combination therapy has more benefits remains controversial. In this study, we provided comparisons to integrate the efficacy of immunotherapy and taxane chemotherapy as second- or later-line treatments in advanced NSCLC. METHODS: PubMed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials were systematically searched from inception to September 1, 2020. Randomized controlled trials comparing immunotherapy and taxane chemotherapy were enrolled in the Bayesian network analysis. Overall survival (OS) and progression-free survival (PFS) with hazard ratios (HRs) were investigated. RESULTS: Eight trials in 13 studies with 4398 patients comparing seven treatments were identified. Pembrolizumab 10 mg/kg was associated with the best improved OS, with significant differences versus docetaxel (HR 0.81, 95% credible interval [CrI] 0.74-0.88), avelumab (HR 0.84, 95% CrI 0.75-0.95), and pembrolizumab 200 mg plus docetaxel (HR 0.75, 95% CrI 0.56-1.00). Although pembrolizumab 200 mg plus docetaxel ranked the last in terms of OS, the combination therapy showed the most favorable PFS. Additionally, the anti-programmed death-ligand 1 (PD-L1) agent, avelumab, was associated with the least improvement in PFS. CONCLUSION: As second- or later-line therapeutic strategies, pembrolizumab 10 mg/kg provided the largest OS benefits and pembrolizumab 200 mg plus docetaxel improved PFS to the greatest extent. Considering that immunotherapy has been recommended to the first-line setting of NSCLC, advanced patients who have not received immunotherapy previously might be the suitable population for our findings.

The Multimodal Ultrasound Features of Ovarian Serous Surface Papillary Borderline Tumor.

Aim: Ovarian serous surface papillary borderline tumor (OSSPBT) is very rare. Combined with clinical and pathological features, we aim to investigate the multimodal ultrasound features of OSSPBT. Patients and Methods: There were only 18 patients diagnosed with OSSPBT among the 142 patients who were diagnosed with borderline serous ovarian tumor by pathology from June 2008 to December 2020 in our hospital. Their clinical data, conventional ultrasound, two-dimensional contrast-enhanced ultrasound (2D-CEUS), three-dimensional contrast-enhanced ultrasound (3D-CEUS) characteristics, pathology, and prognosis were retrospectively analyzed. Results: The 18 patients had no specific clinical symptoms. Multiple implantable nodules were found in 8 patients (44.4%), ascites in 13 patients (72.2%), and elevated carbohydrate antigen 125 (CA125) in 15 patients (83.3%). After excluding 2 misdiagnosed patients from 18 patients, 26 tumors in 16 patients (6 unilateral and 10 bilateral) were studied. Conventional ultrasound findings of OSSPBT showed that large solid masses around normal ovary without capsule, and numerous small dense anechoic areas were observed in the parenchyma of the lesion, with strong speckle echo ("blizzard" sign) of varying degrees. The 2D-CEUS and 3D-CEUS showed a normal ovary in the center surrounded by a radial blood supply of OSSPBT with thick and irregular branches. Histopathologically, the papillary fibrous stalk of OSSPBT had a large number of sand bodies and tortuous dilated microvessels. All patients had no recurrence after surgery, and two of them delivered successfully through assisted reproductive technology. Conclusion: OSSPBT has a good prognosis. Its conventional ultrasound is characterized by irregular solid masses surrounding normal ovaries and a large number of "blizzard" signs. It showed low enhancement of eccentricity with irregular radial branches centered on the ovary by CEUS.

Poziotinib in non-small-cell lung cancer patients with HER2 exon 20 mutations: A pooled analysis of randomized clinical trials.

BACKGROUND: Non-small-cell lung cancer (NSCLC) harboring human epidermal growth factor receptor 2 (HER2) exon 20 mutant occurs in 3% of NSCLCs. Targeted agents for this population remain an unmet need. In this analysis, we pooled-analyzed the efficacy and safety of poziotinib, a novel tyrosine kinase inhibitor, in HER2 exon 20 mutant NSCLC. METHODS: PubMed, Embase, Web of Science, and Cochrane CENTRAL databases were systematically searched on March 9, 2022. The primary endpoints were objective response rate (ORR) and disease control rate. The secondary endpoint was treatment-related adverse events. RESULTS: Three prospective clinical trials, involving 126 patients, were identified. The pooled ORR and disease control rate of poziotinib in HER2 exon 20 mutant NSCLC were 27% (95% CI, 19-35) and 72% (95% CI, 64-80), respectively. Patients with G778_P780dupGSP had the highest ORR (88%; 95% CI, 33-100; n = 12), followed by Y772_A775dupYVMA (20%; 95% CI, 12-30; n = 88) and G776delinsVC (19%; 95% CI, 0-50; n = 13). The most common grade 3 to 4 treatment-related adverse events were skin rash (36%), diarrhea (23%), and oral mucositis (13%). CONCLUSION: Poziotinib demonstrates moderate antitumor activity in previously treated HER2 exon 20 mutant NSCLC patients with a manageable safety profile. In addition, different subgroup mutations show various benefits of poziotinib treatment. Large-scale and multiarm clinical trials are warranted to confirm a suitable population and therapeutic strategies.

Induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma: A systematic review and meta-analysis.

Background: Adding induction chemotherapy to concurrent platinum-based chemoradiotherapy has significantly prolonged the survival time of patients with locoregionally advanced nasopharyngeal carcinoma. In this study, we intend to evaluate the survival outcomes, responses, and incidences of toxicities of induction chemotherapy and the differences between different strategies. Methods: A comprehensive search was conducted in PubMed, Embase, Web of Science, and Cochrane CENTRAL on August 10, 2021. Single-arm or multi-arm prospective clinical trials on induction chemotherapy without targeted therapies or immune checkpoint inhibitors were included. Primary outcomes included survival outcomes, objective response rate, and disease control rate, and the secondary outcome was the rates of grade 3 or higher treatment-related adverse events. Results: The 39 studies included in the systematic review and meta-analysis comprised 36 clinical trials and 5389 patients. The estimates for 3-year overall and fail-free survival rates were 87% and 77%. The estimates for 5-year rates of overall and fail-free survival were 81% and 73%. Gemcitabine plus platinum and docetaxel combined with 5-fluorouracil plus platinum strategies were associated with the highest rates of 3-year and 5-year overall survival. The objective response and disease control rates were 85% and 98% after the completion of induction chemotherapy. Neutropenia (27%) and nausea/vomiting (7%) were the most common grade 3 or higher treatment-related hematological and non-hematological adverse events during the induction phase. Conclusions: Different induction chemotherapeutic strategies appear to have varying effects and risks; a comprehensive summary of the survival outcomes, responses, and toxicities in clinical trials may provide a crucial guide for clinicians.