Extreme terahertz magnon multiplication induced by resonant magnetic pulse pairs.

Nonlinear interactions of spin-waves and their quanta, magnons, have emerged as prominent candidates for interference-based technology, ranging from quantum transduction to antiferromagnetic spintronics. Yet magnon multiplication in the terahertz (THz) spectral region represents a major challenge. Intense, resonant magnetic fields from THz pulse-pairs with controllable phases and amplitudes enable high order THz magnon multiplication, distinct from non-resonant nonlinearities such as the high harmonic generation by below-band gap electric fields. Here, we demonstrate exceptionally high-order THz nonlinear magnonics. It manifests as 7th-order spin-wave-mixing and 6th harmonic magnon generation in an antiferromagnetic orthoferrite. We use THz two-dimensional coherent spectroscopy to achieve high-sensitivity detection of nonlinear magnon interactions up to six-magnon quanta in strongly-driven many-magnon correlated states. The high-order magnon multiplication, supported by classical and quantum spin simulations, elucidates the significance of four-fold magnetic anisotropy and Dzyaloshinskii-Moriya symmetry breaking. Moreover, our results shed light on the potential quantum fluctuation properties inherent in nonlinear magnons.

[Analysis of the relationship between PI-RADS scores and the pathological results of targeted biopsy based on MRI].

Objective: To analyze the relationship between Prostate Imaging Reporting and Data System (PI-RADS) scores and the pathological results of transperineal magnetic resonance-ultrasound fusion guided biopsy. Methods: The clinical data, magnetic resonance imaging (MRI) results and prostate puncture biopsies of 517 patients who were assigned to PI-RADS score of 4 or 5 and underwent transperineal magnetic resonance-ultrasound fusion guided biopsy at The First Affiliated Hospital of Nanjing Medical University from June 2019 to March 2022 were retrospectively analyzed. Patients were divided into the PI-RADS 4 and PI-RADS 5 groups according to their PI-RADS scores and were stratified by their prostate specific antigen (PSA) values (PSA<10 ng/ml vs. PSA 10-20 ng/ml). The pathological negative rates from the biopsy, the distribution of the grade groups according to the grading system by World Health Organization/International Society of Urological Pathology (WHO/ISUP), the detection rates of prostate cancer (PCa) and clinically significant prostate cancer (CsPCa)between the groups were compared. Results: 369 patients with a PI-RADS score of 4 and 148 patients with a PI-RADS score of 5 were included in our research. The overall detection rates of PCa and CsPCa were 77.8% (402/517) and 66.7% (345/517), respectively. In the PI-RADS 4 group, patients with prostate negative biopsies or in WHO/ISUP 1, 2, 3, 4, or 5 grade groups accounted for 28.2%, 12.7%, 20.1%, 17.1%, 18.4% and 3.5%, respectively, whereas in the PI-RADS 5 group the rates were 7.4%, 6.8%, 22.3%, 22.3%, 26.4%, and 14.9%, respectively. The difference was statistically significant (P<0.001). The detection rates of PCa and CsPCa in the PI-RADS 4 group [71.8% (265/369) vs. 59.1% (218/369), P<0.001] were lower than those of the PI-RADS 5 group [92.6% (137/148) vs. 85.8% (127/148), P<0.001]. In the PI-RADS 4 group, the proportion of patients classified into WHO/ISUP 4-5 grade groups was lower than that of patients in the PI-RADS 5 group [22.0% (81/369) vs 41.2% (61/148) (P<0.001)]. The detection rates of PCa and CsPCa in the PSA<10 ng/ml stratification were less than that in the PSA 10-20 ng/ml stratification[74.1% (281/379) vs. 87.7% (121/138), P=0.001], and [60.9% (231/379) vs. 82.6% (114/138), P<0.001]. For patients with PSA<10 ng/ml, the detection rates of PCa and CsPCa in the PI-RADS 4 group were less than those in the PI-RADS5 group [70.9% (217/306) vs. 87.7% (64/73), P=0.003], and [56.2% (172/306) vs. 80.8% (59/73), P<0.001]. For those with a PSA value of 10-20 ng/ml, the detection rates of PCa and CsPCa in the PI-RADS 4 group were less than those in the PI-RADS 5 group [76.2% (48/63) vs. 97.3% (73/75), P<0.001], and [73.0% (46/63) vs. 90.7% (68/75), P=0.006]. There were statistically significant differences in the proportions of patients with prostate negative biopsy and those falling into WHO/ISUP grade groups 1, 2, 3, 4, or 5 (P<0.001) between the PI-RADS 4 group and the PI-RADS 5 group in both stratifications. Conclusions: In this study, the detection rates of CsPCa and PCa in the PI-RADS 4 group were less than those in the PI-RADS 5 group. With the increase of PI-RADS scores, the detection rate of high-grade PCa increased. The same results held for patients with PSA<10 ng/ml or with PSA 10-20 ng/ml.

[Changes of HER2 low expression status in primary and recurrent/metastatic breast cancer].

Objective: To investigate the evolution and clinical significance of HER2 low expression status in HER2 negative patients in primary and recurrent/metastatic breast cancers. Methods: The data and archived sections of 259 breast cancer patients with recurrence/metastasis and HER2-negative primary foci were collected from January 2015 to January 2022 at the Fourth Hospital of Hebei Medical University, and the HER2 status of primary and recurrence/metastasis foci was determined by immunohistochemistry (IHC), among which IHC 2+patients were subject to fluorescence in situ hybridization (FISH). The HER2 status was classified as HER2-0 group; patients with IHC 1+, IHC 2+and no FISH amplification were classified as HER2 low expression group; and patients with IHC 3+, IHC 2+and FISH amplified were classified as HER2-positive group. The changes of HER2 status in patients with HER2 low expression in primary versus recurrent/metastatic breast cancer foci were compared, and their clinicopathologic characteristics and prognosis were analyzed. Results: The overall concordance rate between primary and recurrent/metastatic HER2 status in breast cancer was 60.6% (157/259, κ=0.178). A total of 102 patients (102/259, 39.4%) had inconsistent primary and recurrent/metastatic HER2 status; 37 patients (37/259, 14.3%) had HER2-0 at the primary foci and HER2-low expression at the recurrent/metastatic; and 56 patients (56/259, 21.6%) had HER2-low expression in the primary foci and HER2-0 in the recurrent/metastatic. The recurrent/metastatic foci became low-expressing compared with the recurrent/metastatic foci which remained HER2-0 patients, with longer overall survival time, higher ER and PR positivity, lower Ki-67 positivity index, and lower tumor histological grade; all with statistically significant differences (all P<0.05). In the primary HER2-low group, patients with recurrent/metastatic foci became HER2-0 while those with recurrent/metastatic foci remained low expression; there were no statistically significant differences in clinicopathological features and overall survival time (all P>0.05). Conclusions: Unstable HER2 status in patients with HER2-0 and low expression in primary versus recurrent/metastatic breast cancer foci, and HER2-0 in the primary foci but low HER2 expression status in recurrence/metastasis is associated with favourable prognosis, and testing HER2 status in recurrence/metastasis can provide more treatment options for such patients.

[Efficacy and safety of VRD regimen of autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma].

Objective: To explore the stem cell collection rate and efficacy and safety of patients aged 70 and below with newly diagnosed multiple myeloma (MM) treated with the VRD (bortezomib, lenalidomide and dexamethasone) regimen followed by autologous stem cell transplantation (ASCT). Methods: Retrospective case series study. The clinical data of 123 patients with newly diagnosed MM from August 1, 2018, to June 30, 2020, at the First Affiliated Hospital of Soochow University and Suzhou Hopes Hematology Hospital, who were eligible for VRD regimen sequential ASCT, were collected. The clinical characteristics, efficacy after induction therapy, mobilization regimen of autologous stem cells, autologous stem cell collection rate, and side effects and efficacy of ASCT were retrospectively analyzed. Results: Of the 123 patients, 67 were males. The median patient age was 56 (range: 31-70) years. Patients with IgG, IgA, IgD, and light-chain types accounted for 47.2% (58/123), 23.6% (29/123), 3.2% (4/123), and 26.0% (32/123) of patients, respectively. In addition, 25.2% (31/123) of patients had renal insufficiency (creatinine clearance rate<40 ml/min). Patients with Revised-International Staging System (R-ISS) Ⅲ accounted for 18.2% (22/121) of patients. After induction therapy, the rates of partial response and above, very-good partial response (VGPR) and above, and complete response (CR)+stringent CR were 82.1% (101/123), 75.6% (93/123), and 45.5% (56/123), respectively. Overall, 90.3% (84/93) of patients were mobilized with cyclophosphamide+granulocyte colony-stimulating factor (G-CSF) and 8 patients with G-CSF or G-CSF+plerixafor due to creatinine clearance rate<30 ml/min and one of them was mobilized with DECP (cisplatin, etoposide, cyclophosphamide and dexamethasone)+G-CSF for progressive disease. The rate of autologous stem cell collection (CD34+cells≥2×106/kg) after four courses of VRD regimen was 89.1% (82/92), and the rate of collection (CD34+cells≥5×106/kg) was 56.5% (52/92). Seventy-seven patients treated with the VRD regimen sequential ASCT. All patients had grade 4 neutropenia and thrombocytopenia. Among the nonhematologic adverse events during ASCT, the highest incidence was observed for gastrointestinal reactions (76.6%, 59/77), followed by oral mucositis (46.8%, 36/77), elevated aminotransferases (44.2%, 34/77), fever (37.7%, 29/77), infection (16.9%, 13/77) and heart-related adverse events (11.7%, 9/77). Among the adverse events, grade 3 adverse events included nausea (6.5%, 5/77), oral mucositis (5.2%, 4/77), vomiting (3.9%, 3/77), infection (2.6%, 2/77), elevated blood pressure after infusion (2.6%, 2/77), elevated alanine transaminase (1.3%, 1/77), and perianal mucositis (1.3%, 1/77); there were no grade 4 or above nonhematologic adverse events. The proportion of patients who achieved VGPR and above after VRD sequential ASCT was 100% (75/75), and the proportion of patients who were minimal residual disease-negative (<10-4 level) was 82.7% (62/75). Conclusion: In patients aged 70 and below with newly diagnosed MM treated with VRD induction therapy, the collection rate of autologous stem cells was good, and good efficacy and tolerability were noted after follow-up ASCT.

[Analysis of therapeutic mechanism of Liushen Wan against colitis-associated colorectal cancer based on network pharmacology and validation in mice].

OBJECTIVE: To explore the therapeutic mechanism of Liushen Wan (LSW) against colitis-associated colorectal cancer (CAC) by network pharmacology. METHODS: TCMSP, BATMAN-TCM, CNKI, PubMed, Genecards, OMIM, and TTD databases were used to obtain the related targets of LSW and CAC. The common targets of LSW and CAC were obtained using Venny online website. The PPI network was constructed using Cytoscape 3.8.2 to screen the core targets of LSW in the treatment of CAC. GO and KEGG enrichment analysis were conducted using DAVID database. The therapeutic effect of LSW on CAC was evaluated in a C57BL/6J mouse model of AOM/DSS-induced CAC by observing the changes in body weight, disease activity index, colon length, and size and number of the tumor. HE staining and RT-qPCR were used to analyze the effect of LSW on inflammatory mediators. Immunohistochemistry and TUNEL staining were used to evaluate the effect of LSW on the proliferation and apoptosis of AOM/DSS-treated colon tumor cells. Immunohistochemistry and Western blotting were used to detect the effects of LSW on the expression of TLR4 proteins in CAC mice. RESULTS: Network pharmacology analysis identified 69 common targets of LSW and CAC, and 33 hub targets were screened in the PPI network. KEGG pathway enrichment analysis suggested that the effect of LSW on CAC was mediated by the Toll-like receptor signaling pathway. In the mouse model of AOM/DSS-induced CAC, LSW significantly inhibited colitis-associated tumorigenesis, reduced tumor number and tumor load (P < 0.05), obviously improved histopathological changes in the colon, downregulated the mRNA levels of proinflammatory cytokines, and inhibited the proliferation (P < 0.01) and promoted apoptosis of colon tumor cells (P < 0.001). LSW also significantly decreased TLR4 protein expression in the colon tissue (P < 0.05). CONCLUSION: LSW can inhibit CAC in mice possibly by regulating the expression of TLR4 to reduce intestinal inflammation, inhibit colon tumor cell proliferation and promote their apoptosis.

[Primary cardiac angiosarcoma: a clinicopathological and molecular genetic analysis of thirteen cases].

Objective: To investigate the clinicopathological and molecular features of primary cardiac angiosarcoma (PCAS), and to analyze the correlation between KDR mutation and the clinicopathological features of PCAS. Methods: Thirteen cases of PCAS were collected at Beijing Anzhen Hospital, Capital Medical University from January 2007 to December 2021. The clinicopathological features, diagnosis, differential diagnosis and outcome were retrospectively analyzed. KDR mutation was detected by next-generation sequencing (NGS) and then the expression of KDR (VEGFR2) was determined by immunohistochemistry (IHC), with review of relevant literatures. Results: There were eight males and five females with a mean age of 45 years. The primary tumor was in the right atrium in 10 cases, left atrium in two cases and right ventricle in one case. The histomorphology was mainly poorly differentiated angiosarcoma (11 cases), with highly pleomorphic spindle or round cells in solid sheets, brisk mitotic activity and extensive necrosis. Vascular lumen formation was observed in two cases of high to moderate differentiation, and biphenotypic differentiation was seen in five cases. IHC staining showed CD34, CD31, Fli1, ERG and vimentin were diffusely positive, pan-cytokeratin was positive, Ki-67 index ranged from 3% to 90%, which was positively correlated with the differentiation degree and grade of the PCASs (P<0.05). At the end of follow-up period, one patient was alive, two patients were lost to follow-up, and the remaining 10 patients had an average survival time of 4.6 months. Finally, NGS sequencing was performed on seven samples after screening, and the results showed that KDR and NF1 mutations were both present in three cases. VEGFR2 expression had no significant correlation with the differentiation degree and grade of PCAS (P>0.05), and it was not related to KDR mutation. Conclusions: PCASs mainly occur in the right atrium, and are mainly poorly differentiated. Ki-67 index is helpful to assess the degree and grade of tumor differentiation. The occurrence and development of PCAS may be related to the pathway involved in KDR mutation, but KDR mutation has no clear correlation with clinicopathological characteristics of PCAS, and immunohistochemical staining can not replace gene detection to determine whether the tumor had KDR mutation.

Neuroimaging of complications arising after CD19 chimeric antigen receptor T-cell therapy: A review.

Chimeric antigen receptor (CAR) T cells targeting the CD19 (cluster of differentiation 19) cell surface glycoprotein have emerged as a highly effective immunologic therapy in patients with relapsed or refractory B-cell malignancies. The engagement of CAR T cells with CD19 on the surface of neoplastic B cells causes a systemic cytokine release, which can compromise the blood-brain barrier and cause an immune effector cell-associated neurotoxicity syndrome (ICANS). In a small proportion of ICANS patients who demonstrate neuroimaging abnormalities, certain distinct patterns have been recognized, including signal changes in the thalami, external capsule, and brainstem, the subcortical and/or periventricular white matter, the splenium of the corpus callosum, and the cerebellum. On careful review of the underlying pathophysiology of ICANS, we noticed that these changes closely mirror the underlying blood-brain barrier disruption and neuroinflammatory and excitotoxic effects of the offending cytokines released during ICANS. Furthermore, other uncommon complications of CD19 CAR T-cell therapy such as posterior reversible encephalopathy syndrome, ocular complications, and opportunistic fungal infections can be catastrophic if not diagnosed in a timely manner, with neuroimaging playing a significant role in management. In this narrative review, we will summarize the current literature on the spectrum of neuroimaging findings in ICANS, list appropriate differential diagnoses, and explore the imaging features of other uncommon central nervous system complications of CD19 CAR T-cell therapy using illustrative cases from two tertiary care institutions.

[Clinical characteristics and placental pathology analysis of 14 cases of pregnancy with aortic dissection/aortic aneurysm].

Objective: To investigate the pathological changes of placenta in pregnant women with aortic dissection/aneurysm and their relationship with clinical features. Methods: The placental samples of 14 pregnant women with aortic dissection/aneurysm diagnosed from January 2012 to October 2021 and 10 normal placental samples of pregnant women from January 2021 to December 2021 at Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing, China were selected. Routine H&E staining and immunohistochemistry were used to analyze the histological features under light microscope. The clinical data were also analyzed. Results: The age of 14 pregnant patients with aortic dissection/aneurysm for placental examination ranged from 22 to 38 years (median, 28 years). The gestational ages ranged from 22 to 39 weeks (median, 34 weeks). The pregnancy of second trimester was noted in 2 cases, and the third trimester in 12 cases. All cases were singleton pregnancy. Seven cases were Stanford type A aortic dissection, 6 cases were Stanford type B aortic dissection, and one case was aortic root aneurysm. Four of the pregnant women underwent aortic dissection surgery after caesarean section, three underwent caesarean section after aortic dissection surgery, and seven underwent both caesarean section and aortic dissection procedures. Among the newborns, 2 cases were full-term birth, and 12 cases were premature birth. Twelve cases had alive newborns, and 2 cases stillbirths. Fetal/placental weight ratio (FPR)<10th percentile was in 5 cases and FPR>90th percentile in one case. Compared with the normal group, accelerated villus maturation and distal villus dysplasia were more frequently found in pregnancy with aortic dissection group (P<0.05). There was no significant difference in villi infarction and decidua vascular lesions between the two groups (P>0.05), nor was there correlation between the type of aortic dissection and distal villus dysplasia and accelerated villus maturation of placentas (P>0.05). The number of villous interstitial blood vessels in the placentas of pregnancy with aortic dissection group was significantly fewer than that in the normal control group (P<0.01). Conclusions: There are considerable pathological changes in the placentas of pregnant women with aortic dissection/aneurysm. The main histological features are accelerated villus maturation and distal villus dysplasia, which are manifestations of villous ischemia and hypoxia, and also a part of the placental pathological manifestations of maternal vascular dysperfusion.

[Effects of three medical nutrition therapies for weight loss on metabolic parameters and androgen level in overweight/obese patients with polycystic ovary syndrome].

Objective: To investigate the effects of calorie-restricted diet (CRD), high protein diet (HPD), high protein, and high dietary fiber diet (HPD+HDF) on metabolic parameters and androgen level in overweight/obese patients with polycystic ovary syndrome(PCOS). Methods: Ninety overweight/obese patients with PCOS from Peking University First Hospital from October 2018 to February 2020 were given medical nutrition weight loss therapy for 8 weeks and were randomly divided into CRD group, HPD group, and HPD+HDF group, with 30 patients in each group. Body composition, insulin resistance, and androgen level were detected before and after weight loss, and the efficacy of three weight loss therapies was compared through variance analysis and Kruskal-Wallis H test. Results: Eight patients in CRD group quit because they could not strictly complete the follow-up, therefore at the end of weight loss, 22, 30, and 30 patients in CRD group, HPD group and HPD+HDF group, respectively, were included in the final analysis. The baseline ages of the three groups were (31±2) years, (32±5) years and (31±5) years, respectively (P=0.952). After weight loss, the relevant indicators in HPD group and HPD+HDF group decreased more than those in CRD group. The body weight of CRD group, HPD group and HPD+HDF group decreased by 4.20 (11.92, 1.80), 5.00 (5.10, 3.32) and 6.10 (8.10, 3.07) kg, respectively (P=0.038); BMI of the three groups decreased by 0.80 (1.70, 0.40), 0.90 (1.23, 0.50) and 2.20 (3.30, 1.12) kg/m2, respectively (P=0.002); homeostatic model assessment-insulin resistance(HOMA-IR) index decreased by 0.48(1.93, 0.05), 1.21(2.91, 0.18) and 1.22(1.75, 0.89), respectively (P=0.196); and free androgen index(FAI) decreased by 0.23(0.67, -0.04), 0.41(0.64, 0.30) and 0.44(0.63, 0.24), respectively (P=0.357). Conclusions: The three medical nutrition therapies can effectively reduce the weight of overweight/obese patients with PCOS, and improve insulin resistance and hyperandrogenism. Compared with CRD group, HPD group, and HPD+HDF group have better fat-reducing effect, and can better preserve muscle and basal metabolic rate while losing weight.

[Schistosomiasis control in Sichuan Province since the 12th Five - Year Plan period: progress and prospects].

An ambitious goal has been set for elimination of schistosomiasis in all endemic counties (districts) in Sichuan Province by 2023. To achieve this goal, and to continue to consolidate the control achievements, it is necessary to understand the current endemic status of schistosomiasis, identify the challenges and analyze the experiences and lessons from the schistosomiasis control program, and develop targeted control strategies and interventions in the province. This paper reviews the progress of schistosomiasis control in Sichuan Province since the 12th Five-Year Plan period, analyzes the challenges in the schistosomiasis elimination program, and proposes recommendations for future directions and priorities.

Quantitative Susceptibility Mapping: Translating an Investigative Research Tool into High Volume Clinical Diagnostic Imaging.

Quantitative susceptibility mapping (QSM) is an MRI-based technique for iron quantification of targeted tissue. QSM provides information relevant to clinicians in a broad range of diagnostic contexts, including sickle cell disease, inflammatory/demyelinating processes, and neoplasms. However, major MRI vendors do not offer QSM post-processing in a form ready for general use. This work describes a vendor-agnostic approach for scaling QSM analysis from a research technique to a routine diagnostic test. We provide the details needed to seamlessly integrate hardware, software, and clinical systems to provide QSM processing for a busy clinical radiology workflow. This approach can be generalized to other advanced MRI acquisitions and analyses with proven diagnostic utility, yet without crucial MR vendor support.

[Analysis of hepatic pathological inflammation and fibrosis condition and its influencing factors in 721 patients with chronic hepatitis B with normal ALT].

Objective: To analyze the hepatic pathological inflammation and fibrosis condition in order to explore the relationship with related clinical indicators in patients with chronic hepatitis B patients with normal alanine aminotransferase (ALT). Methods: 721 cases of chronic hepatitis B with normal ALT who were initially diagnosed in the Department of Infectious Diseases of Henan Provincial People's Hospital from August 2016 to December 2019 were retrospectively collected. Liver biopsy was performed in all patients. General data of patients such as gender, age, liver function indexes, blood routine indexes, HBsAg level, HBeAg status, HBV DNA level, spleen thickness and prothrombin time were collected. Univariate and multivariate analysis methods were used to determine the influencing factors of inflammation and fibrosis degree with liver biopsy. A receiver operating characteristic curve (ROC) was used to evaluate the established multi-factor prediction model. Alpha=0.05 was considered as a standard orientation of test. Results: The average age of 721 cases with chronic hepatitis B was 36.1±9.7 years, and the male to female ratio was 1.28/1, with inflammation and fibrosis grade mainly concentrated in G1S1 (349 cases), G1S2 (132 cases), G2S2 (119 cases), and G2S1 (57 cases). Among them, there were 349 (48.4%) cases of G1S1, and 372 (51.6%) cases of G/S≥2. The main manifestations were mild to moderate inflammation and fibrosis, and only 64 (8.88%) cases had severe G/S≥3. HBsAg level (stratified with 4 log10 IU/ml as the boundary) analyzed in 721 cases were correlated with the relevant clinical indicators stratification and liver pathological inflammation and fibrosis, and the difference was statistically significant (inflammation grade, χ2=6.182, P=0.013; Fibrosis grade, χ2=36.534, P=0.001). Univariate analysis of the relevant clinical indicators that may influence the patient's liver pathological G/S ≥2 showed the patient's age, albumin, γ- glutamyltransferase (GGT), platelet, prothrombin time (PT), spleen thickness and HBsAg level were all statistically significant (P<0.05), while multivariate analysis showed that age, GGT, PT, and spleen thickness had statistical differences (P<0.05). The prediction model was established in accordance to multivariate analysis, and the area under the ROC curve was 0.642. Maximization of the sum of sensitivity and specificity as cut-off value of Logit P=0.497, the diagnostic sensitivity, specificity, and Youden's index were 60.6%, 64.5%, and 0.252, respectively. Conclusion: More than half of patients with chronic hepatitis B with normal ALT have significant inflammation and fibrosis and require timely antiviral therapy. Age, GGT, PT and spleen thickness can help comprehensively evaluate the liver inflammation and fibrosis status among patients, but the lack of accurate prediction models suggests that more effective indicators that can help predict the inflammation and fibrosis status of such patients have yet to be discovered. Therefore, liver biopsy should still be actively performed in patients with normal ALT to confirm the diagnosis and timely treatment.

[The expression level of secretory mature B cell surface antigen in primary diagnosed multiple myeloma and its clinical significance].

Objective: To explorer Secretory mature B cell surface antigen (sBCMA) expression level, changes during treatment and clinical significance in newly diagnosed MM patients. Methods: Clinical data of 158 MM patients admitted to the Department of Hematology, the First Affiliated Hospital of Soochow University from August 2018 to September 2020 were analyzed retrospectively. The concentration of sBCMA in the patients was determined by BCMA ELISA and compared with the normal range. The results were compared with clinical efficacy, age, type, R-ISS stage, renal impairment, and humoral immune function. Results: The median age of the patients was 57 (31-73 years old), 86 (54.5%) males and 72 (45.5%) females, mainly IgG type, 81 patients(51.2%). SBCMA value M(Q1,Q3) was 76.50 (55.50, 94.40) µg/L, 100% higher than the upper limit of normal value. According to the efficacy evaluation, the patients were divided into complete remission(CR) group, very good partial remission(VGPR) group, partial remission(PR) group and ineffiecacy group, the results showed the level of sBCMA in CR group[80.10 (58.05, 96.90) vs 15.70 (9.85, 28.65) µg/L] and VGPR group[74.60 (52.20, 93.00) vs 17.20 (13.30, 38.80) µg/L]was significantly higher than that before treatment(all P<0.001), and there was no significant difference in PR group and ineffective group before and after treatment (all P>0.05).The amount of serum intact protein M protein was positively correlated with the level of sBCMA expression in newly diagnosed patients (r=0.22, P=0.040), and there was no correlation between the proportion of bone marrow plasma cells and sBCMA expression (r=0.07, P=0.449).The correlation between sBCMA levels at initial diagnosis and MM type[IgG type, IgA type vs light chain type:(78.6±3.5), (72.4±5.4) vs (83.8±6.9)µg/L], age[≥65 vs<65 years: (73.6±5.5)vs (79.3±3.1)µg/L], R-ISS stage[stage Ⅰ, Ⅱ vs Ⅲ:(80.2±3.1) vs (69.4±6.1)µg/L], renal impairment [Creatinine clearance rate (Ccr) ≤30 vs>30 ml/min:(81.6±4.8) vs (76.5±3.4)µg/L], and high-risk karyotype[high-risk vs standard-risk:(73.6±5.7) vs (80.2±3.2)µg/L] were not associated (all P>0.05). Expression levels of sBCMA were negatively correlated with IgM levels in MM patients (r=-0.39, P=0.002) and after treatment (r=-0.25, P=0.015). Conclusions: The expression of sBCMA in MM patients is a reliable indicator of the clinical efficacy of MM and is related to the occurrence of MM immune deficiency and recovery after treatment. sBCMA can be used as a new independent marker for monitoring and predicting the efficacy of MM patients.

Ultra-high field 7 T MRI localizes regional brain volume recovery following corticotroph adenoma resection and hormonal remission in Cushing's disease: A case series.

Background: Cushing's disease (CD) is defined by glucocorticoid excess secondary to the increased section of corticotropin by a pituitary adenoma. Magnetic resonance imaging (MRI) studies performed at 1.5 or 3 Tesla (T) have demonstrated correlations between regional changes in brain structure and the progression of CD. In this report, we examine the changes in brain volume following corticotroph pituitary adenoma resection using ultra-high field 7 T MRI to increase the accuracy of our volumetric analyses. Methods: Thirteen patients were referred to the endocrinology clinic at our institution from 2017 to 2020 with symptoms of cortisol excess and were diagnosed with ACTH-dependent endogenous Cushing syndrome. Five patients had follow-up 7 T imaging at varying time points after a transsphenoidal resection. Results: Symmetrized percent change in regional volumes demonstrated a postoperative increase in cortical volume that was relatively larger than that of cerebral white matter or subcortical gray matter (percent changes = 0.0172%, 0.0052%, and 0.0120%, respectively). In the left cerebral hemisphere, the medial orbitofrontal, lateral orbitofrontal, and pars opercularis cortical regions experienced the most robust postoperative percent increases (percent changes = 0.0166%, 0.0122%, and 0.0068%, respectively). In the right cerebral hemisphere, the largest percent increases were observed in the pars triangularis, rostral portion of the middle frontal gyrus, and superior frontal gyrus (percent changes = 0.0156%, 0.0120%, and 0.0158%). Conclusion: Cerebral volume recovery following pituitary adenoma resection is driven by changes in cortical thickness predominantly in the frontal lobe, while subcortical white and gray matter volumes increase more modestly.

[A clinical retrospective analysis of newly diagnosed multiple myeloma patients with systemic light chain amyloidosis].

Objective: To analyze the clinical characteristics, treatment response, and prognosis of newly diagnosed symptomatic multiple myeloma (MM) patients with systemic light chain amyloidosis (AL) . Methods: The clinical data of 160 patients with newly diagnosed MM treated at the First Affiliated Hospital of Soochow University from January 1, 2017 to October 31, 2018, were retrospectively analyzed. According to the histopathological biopsy results of bone marrow, skin, and other tissues, the patients were divided into two groups according to whether amyloidosis was combined or not, namely, the MM+AL group and the MM group. The clinical characteristics and treatment responses of the two groups were compared. Results: Among the 160 patients with newly diagnosed MM, there were 42 cases in the MM+AL group and 118 cases in the MM group. In terms of clinical features, the involved light chain and non-involved light chain (dFLC) in the MM+AL group was significantly higher than that in the MM group (P=0.039) . After induction treatment, the MM+AL group had a higher overall response rate (85.7%vs 79.7%, P<0.05) and higher excellent partial response (76.2%vs 55.1%, P<0.05) . After a median follow-up of 26 (0.25-41) months, there was no significant difference in the progression free survival and overall survival (OS) between the two groups (P>0.05) . The OS of patients in autologous hematopoietic stem cell transplantation group was better than that in non transplantation group (P<0.05) .The prognosis of patients with cardiac involvement in the MM+AL group was significantly worse than that in the MM group and MM+AL group without cardiac involvement (P<0.001) , with a median OS of only 13 months. Conclusion: The differential diagnosis between the MM+AL and MM groups requires histopathology, particularly for patients with significantly increased dFLC. The overall remission rate of patients in MM+AL group after 4 courses of induction chemotherapy was higher than that in MM group. The prognosis of patients with cardiac involvement in MM+AL group was poor.

[Clinicopathological characteristics and molecular alterations of primary cardiac leiomyosarcoma: report of five cases].

Objective: To investigate the clinical, pathologic and radiologic features and molecular alterations in patients with primary cardiac leiomyosarcoma (PCLMS). Methods: Five cases of PCLMS were collected in Beijing Anzhen Hospital from January 2016 to December 2020. The clinical, pathologic and radiologic data, and molecular alterations were analyzed, and the patients were followed up. Results: All five patients were female, and had no history of leiomyosarcoma in other parts of the body. The age of patients ranged from 37 to 62 years (median 47 years). The main clinical symptoms were chest pain and dyspnea, one also presented with palpitation and lower limb weakness and one with dizziness. Two tumors were located in the left atrium, two in the right atrium, and one in the right ventricle, and they maximal diameter ranged from 2.5 to 14.0 cm (mean 6.2 cm). The neoplasms presented as medium-echo masses with a broad base in the echocardiography, and as a low-density, solid mass when detected by contrast-enhanced CT. Histologically, two tumors were well-differentiated and three were moderately and poorly differentiated, and two included extensive, loose myxoid stroma. Immunohistochemical staining showed that PCLMS was positive for SMA, desmin, MDM2, and epidermal growth factor receptor. Fluorescence in situ hybridization showed ALK gene rearrangement in two cases, and COL1A1-PDGFB fusion in three cases. All cases received surgical excision and two cases received chemotherapy. Three patients died within 0-11 months (mean survival of 7.7 months) and two patients were alive. Conclusions: PCLMS is a malignant tumor with a high recurrence rate and poor prognosis. These cases may provide useful information to improve the diagnosis and management of PCLMS.

[Analysis of clinical features and etiological diagnostic indices of reproductive age women with hyperandrogenism].

Objective: To investigate the clinical features and the value of different diagnostic indices for etiology in reproductive age women with hyperandrogenism. Methods: The medical records of 96 reproductive age women with hyperandrogenism in the multi-disciplinary team of Peking University First Hospital from January 2020 to April 2021 were collected. The patients were divided into four groups based on final diagnosis: congenital adrenal hyperplasia (CAH) (n=8), polycystic ovary syndrome (PCOS) (n=67), idiopathic hyperandrogenism (n=13) and other specific diseases (n=8), respectively. The indices related to androgens in different groups were compared, and then their efficiency for diagnosis of CAH and PCOS were analyzed with receiver operator characteristic curve (ROC curve). Results: A total of 96 patients with hyperandrogenism were recruited, with the age of 19-45 (29±6) years old. Overall, 4.2% (4/96) of the patients were with single clinical hyperandrogenism, 56.3% (54/96) were with single laboratory hyperandrogenaemia and 39.6% (38/96) were with both. The breakdown into laboratory hyperandrogenaemia subtypes was as follows: only T elevation 22.8% (21/92), only A2 elevation 7.6% (7/92), none DHEAS elevation, only FAI elevation 5.4% (5/92) and elevation of more than one of the androgen indices mentioned above accounted for 64.1% (59/92). In the reasons of consultation, simple irregular menstruation (36.0%, 32/89) or accompanied by clinical hyperandrogenism with or without infertility (36.0%, 32/89) were the most common. As for primary visiting departments, Obstetrics and Gynecology accounted for 53.2% (51/96), and then Endocrinology as 39.5% (38/96). The 17-OHP level of CAH, PCOS and idiopathic hyperandrogenism group was 20.0 (8.2, 33.1), 1.1 (0.8, 1.4), 0.9 (0.8, 1.3) ng/ml, respectively. The androstenedione level in these groups was 6.3 (4.6, 8.7), 3.8 (2.9, 4.8) and 3.2 (2.7, 3.7) ng/ml, respectively. The 17-OHP and androstenedione levels of CAH group were significantly higher than that in PCOS or idiopathic hyperandrogenism group (all P<0.05). The ratio of LH and FSH in these three groups was 0.8(0.5, 1.0), 1.3(0.6, 1.9) and 0.6(0.3, 0.7), respectively. The ratio of LH and FSH was significantly higher in PCOS than that in idiopathic hyperandrogenism group (P=0.024), but yet there was no significant difference compared with CAH group (P>0.05). The AUC of ROC curve of 17-OHP for CAH diagnosis was 0.94, followed by androstenedione 0.83, whereas LH/FSH for PCOS diagnosis was only 0.63. Conclusions: Among the reasons of consultation in reproductive age women who visited our multi-disciplinary team for female hyperandrogenism, simple irregular menstruation or accompanied by clinical hyperandrogenism with or without infertility are the most common. PCOS accounts for the majority of different androgen excess disorders. 17-OHP is the most valuable parameter for the diagnosis of CAH and secondly androstenedione.