Toripalimab plus axitinib versus sunitinib as first-line treatment for advanced renal cell carcinoma: RENOTORCH, a randomized, open-label, phase III study.

BACKGROUND: Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC. PATIENTS AND METHODS: Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety. RESULTS: A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimab-axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab-axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab-axitinib group and 58.6% of patients in the sunitinib group. CONCLUSION: In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile TRIAL REGISTRATION: ClinicalTrials.gov NCT04394975.

Machine-learning-based performance comparison of two-dimensional (2D) and three-dimensional (3D) CT radiomics features for intracerebral haemorrhage expansion.

AIM: To investigate the value of non-contrast CT (NCCT)-based two-dimensional (2D) radiomics features in predicting haematoma expansion (HE) after spontaneous intracerebral haemorrhage (ICH) and compare its predictive ability with the three-dimensional (3D) signature. MATERIALS AND METHODS: Three hundred and seven ICH patients who received baseline NCCT within 6 h of ictus from two stroke centres were analysed retrospectively. 2D and 3D radiomics features were extracted in the manner of one-to-one correspondence. The 2D and 3D models were generated by four different machine-learning algorithms (regularised L1 logistic regression, decision tree, support vector machine and AdaBoost), and the receiver operating characteristic (ROC) curve was used to compare their predictive performance. A robustness analysis was performed according to baseline haematoma volume. RESULTS: Each feature type of 2D and 3D modalities used for subsequent analyses had excellent consistency (mean ICC >0.9). Among the different machine-learning algorithms, pairwise comparison showed no significant difference in both the training (mean area under the ROC curve [AUC] 0.858 versus 0.802, all p>0.05) and validation datasets (mean AUC 0.725 versus 0.678, all p>0.05), and the 10-fold cross-validation evaluation yielded similar results. The AUCs of the 2D and 3D models were comparable either in the binary or tertile volume analysis (all p>0.5). CONCLUSION: NCCT-derived 2D radiomics features exhibited acceptable and similar performance to the 3D features in predicting HE, and this comparability seemed unaffected by initial haematoma volume. The 2D signature may be preferred in future HE-related radiomic works given its compatibility with emergency condition of ICH.

Worldwide forest surveys reveal forty-three new species in Phytophthora major Clade 2 with fundamental implications for the evolution and biogeography of the genus and global plant biosecurity.

During 25 surveys of global Phytophthora diversity, conducted between 1998 and 2020, 43 new species were detected in natural ecosystems and, occasionally, in nurseries and outplantings in Europe, Southeast and East Asia and the Americas. Based on a multigene phylogeny of nine nuclear and four mitochondrial gene regions they were assigned to five of the six known subclades, 2a-c, e and f, of Phytophthora major Clade 2 and the new subclade 2g. The evolutionary history of the Clade appears to have involved the pre-Gondwanan divergence of three extant subclades, 2c, 2e and 2f, all having disjunct natural distributions on separate continents and comprising species with a soilborne and aquatic lifestyle and, in addition, a few partially aerial species in Clade 2c; and the post-Gondwanan evolution of subclades 2a and 2g in Southeast/East Asia and 2b in South America, respectively, from their common ancestor. Species in Clade 2g are soilborne whereas Clade 2b comprises both soil-inhabiting and aerial species. Clade 2a has evolved further towards an aerial lifestyle comprising only species which are predominantly or partially airborne. Based on high nuclear heterozygosity levels ca. 38 % of the taxa in Clades 2a and 2b could be some form of hybrid, and the hybridity may be favoured by an A1/A2 breeding system and an aerial life style. Circumstantial evidence suggests the now 93 described species and informally designated taxa in Clade 2 result from both allopatric non-adaptive and sympatric adaptive radiations. They represent most morphological and physiological characters, breeding systems, lifestyles and forms of host specialism found across the Phytophthora clades as a whole, demonstrating the strong biological cohesiveness of the genus. The finding of 43 previously unknown species from a single Phytophthora clade highlight a critical lack of information on the scale of the unknown pathogen threats to forests and natural ecosystems, underlining the risk of basing plant biosecurity protocols mainly on lists of named organisms. More surveys in natural ecosystems of yet unsurveyed regions in Africa, Asia, Central and South America are needed to unveil the full diversity of the clade and the factors driving diversity, speciation and adaptation in Phytophthora. Taxonomic novelties: New species: Phytophthora amamensis T. Jung, K. Kageyama, H. Masuya & S. Uematsu, Phytophthora angustata T. Jung, L. Garcia, B. Mendieta-Araica, & Y. Balci, Phytophthora balkanensis I. Milenkovic, Z. Tomic, T. Jung & M. Horta Jung, Phytophthora borneensis T. Jung, A. Durán, M. Tarigan & M. Horta Jung, Phytophthora calidophila T. Jung, Y. Balci, L. Garcia & B. Mendieta-Araica, Phytophthora catenulata T. Jung, T.-T. Chang, N.M. Chi & M. Horta Jung, Phytophthora celeris T. Jung, L. Oliveira, M. Tarigan & I. Milenkovic, Phytophthora curvata T. Jung, A. Hieno, H. Masuya & M. Horta Jung, Phytophthora distorta T. Jung, A. Durán, E. Sanfuentes von Stowasser & M. Horta Jung, Phytophthora excentrica T. Jung, S. Uematsu, K. Kageyama & C.M. Brasier, Phytophthora falcata T. Jung, K. Kageyama, S. Uematsu & M. Horta Jung, Phytophthora fansipanensis T. Jung, N.M. Chi, T. Corcobado & C.M. Brasier, Phytophthora frigidophila T. Jung, Y. Balci, K. Broders & I. Milenkovic, Phytophthora furcata T. Jung, N.M. Chi, I. Milenkovic & M. Horta Jung, Phytophthora inclinata N.M. Chi, T. Jung, M. Horta Jung & I. Milenkovic, Phytophthora indonesiensis T. Jung, M. Tarigan, L. Oliveira & I. Milenkovic, Phytophthora japonensis T. Jung, A. Hieno, H. Masuya & J.F. Webber, Phytophthora limosa T. Corcobado, T. Majek, M. Ferreira & T. Jung, Phytophthora macroglobulosa H.-C. Zeng, H.-H. Ho, F.-C. Zheng & T. Jung, Phytophthora montana T. Jung, Y. Balci, K. Broders & M. Horta Jung, Phytophthora multipapillata T. Jung, M. Tarigan, I. Milenkovic & M. Horta Jung, Phytophthora multiplex T. Jung, Y. Balci, K. Broders & M. Horta Jung, Phytophthora nimia T. Jung, H. Masuya, A. Hieno & C.M. Brasier, Phytophthora oblonga T. Jung, S. Uematsu, K. Kageyama & C.M. Brasier, Phytophthora obovoidea T. Jung, Y. Balci, L. Garcia & B. Mendieta-Araica, Phytophthora obturata T. Jung, N.M. Chi, I. Milenkovic & M. Horta Jung, Phytophthora penetrans T. Jung, Y. Balci, K. Broders & I. Milenkovic, Phytophthora platani T. Jung, A. Pérez-Sierra, S.O. Cacciola & M. Horta Jung, Phytophthora proliferata T. Jung, N.M. Chi, I. Milenkovic & M. Horta Jung, Phytophthora pseudocapensis T. Jung, T.-T. Chang, I. Milenkovic & M. Horta Jung, Phytophthora pseudocitrophthora T. Jung, S.O. Cacciola, J. Bakonyi & M. Horta Jung, Phytophthora pseudofrigida T. Jung, A. Durán, M. Tarigan & M. Horta Jung, Phytophthora pseudoccultans T. Jung, T.-T. Chang, I. Milenkovic & M. Horta Jung, Phytophthora pyriformis T. Jung, Y. Balci, K.D. Boders & M. Horta Jung, Phytophthora sumatera T. Jung, M. Tarigan, M. Junaid & A. Durán, Phytophthora transposita T. Jung, K. Kageyama, C.M. Brasier & H. Masuya, Phytophthora vacuola T. Jung, H. Masuya, K. Kageyama & J.F. Webber, Phytophthora valdiviana T. Jung, E. Sanfuentes von Stowasser, A. Durán & M. Horta Jung, Phytophthora variepedicellata T. Jung, Y. Balci, K. Broders & I. Milenkovic, Phytophthora vietnamensis T. Jung, N.M. Chi, I. Milenkovic & M. Horta Jung, Phytophthora ×australasiatica T. Jung, N.M. Chi, M. Tarigan & M. Horta Jung, Phytophthora ×lusitanica T. Jung, M. Horta Jung, C. Maia & I. Milenkovic, Phytophthora ×taiwanensis T. Jung, T.-T. Chang, H.-S. Fu & M. Horta Jung. Citation: Jung T, Milenkovic I, Balci Y, Janousek J, Kudlácek T, Nagy ZÁ, Baharuddin B, Bakonyi J, Broders KD, Cacciola SO, Chang T-T, Chi NM, Corcobado T, Cravador A, Dordevic B, Durán A, Ferreira M, Fu C-H, Garcia L, Hieno A, Ho H-H, Hong C, Junaid M, Kageyama K, Kuswinanti T, Maia C, Májek T, Masuya H, Magnano di San Lio G, Mendieta-Araica B, Nasri N, Oliveira LSS, Pane A, Pérez-Sierra A, Rosmana A, Sanfuentes von Stowasser E, Scanu B, Singh R, Stanivukovic Z, Tarigan M, Thu PQ, Tomic Z, Tomsovský M, Uematsu S, Webber JF, Zeng H-C, Zheng F-C, Brasier CM, Horta Jung M (2024). Worldwide forest surveys reveal forty-three new species in Phytophthora major Clade 2 with fundamental implications for the evolution and biogeography of the genus and global plant biosecurity. Studies in Mycology 107: 251-388. doi: 10.3114/sim.2024.107.04.

Role of serum eosinophil cationic protein in distinct endotypes of chronic rhinosinusitis.

BACKGROUND: Serum eosinophil cationic protein (ECP) levels affect the surgical outcome of chronic rhinosinusitis (CRS) with nasal polyps. Primary CRS can be classified into type 2 (T2) and non-T2. We aimed to differentiate the role of serum ECP levels in surgical outcomes between the distinct endotypes of primary CRS. METHODS: We prospectively enrolled patients with bilateral primary CRS who underwent surgical treatment with postoperative follow-up for at least 12 months. Endotyping and serum parameter measurements were completed within 1 week before surgery. RESULTS: In total, 113 patients were enrolled, including 65 with T2 CRS and 48 with non-T2 CRS. Patients in the T2 CRS group with uncontrolled CRS had significantly higher serum ECP levels than those in patients in the non-T2 CRS group. An optimal cut-off value was obtained at 17.0 λg/L using the receiver operating characteristic curve, attaining a sensitivity of 91.7% and specificity of 56.6%. Multivariate logistic regression analysis showed that a higher serum ECP level was an independent factor for postoperative uncontrolled disease. The hazard ratio was 11.3 for the T2 group, with serum ECP levels over 17.0 λg/L. In the non-T2 group, no parameters were significantly correlated with postoperative uncontrolled CRS. CONCLUSIONS: Serum ECP levels appear to be a feasible predictor of postoperative uncontrolled disease in patients with T2 CRS as preoperative serum ECP levels >17.0 λg/L in these patients have an approximately 16.7-fold increased risk of postoperative uncontrolled disease and should be closely monitored.

[Evaluation of visual quality and refractive outcomes of myopia with presbyopia after laser blended vision surgery].

Objective: To investigate the postoperative outcomes and visual quality following laser blended vision (LBV) surgery for the correction of myopia with presbyopia. Methods: This is a prospective study. A total of 50 patients (100 eyes) who underwent LBV surgery for myopia with presbyopia at Beijing Tongren Hospital, Capital Medical University, between August 2021 and March 2022 were included. Uncorrected distance visual acuity (UDVA), uncorrected near visual acuity (UNVA), best-corrected distance visual acuity (BCDVA), manifest refraction spherical equivalent (MRSE) were measured preoperatively and at 1, 3, 6, 12, and 24 months postoperatively for the dominant eye, non-dominant eye, and both eyes. Effectiveness Index (EI) and Safety Index (SI) were calculated to evaluate refractive outcomes. Accommodation function and contrast sensitivity were assessed to evaluate functional vision. Objective visual quality was assessed using higher-order aberrations (HOAs) and a dual-channel visual quality analysis system. Subjective visual quality was evaluated using a questionnaire. Results: At 24 months postoperatively, the EI and SI for the dominant eye were 1.04±0.23 and 1.14±0.14, respectively, while for the non-dominant eye, they were 0.85±0.21 and 1.06±0.08, respectively. Although there were statistically significant differences in UNVA between the eyes at 1 and 3 months postoperatively (all P<0.05), no significant differences were observed from 6 months onward (all P>0.05). At 6 months postoperatively, the UNVA for the dominant and non-dominant eyes were 0.07±0.13 and 0.03±0.13, respectively, with no significant difference (P>0.05). MRSE showed no significant differences at any follow-up time points up to 24 months. Accommodation function did not decrease compared to preoperative levels at any postoperative follow-up. Increases in HOAs were primarily due to spherical aberrations, and there were no significant differences in objective visual quality before and after surgery. Contrast sensitivity improved significantly at 24 months postoperatively compared to preoperative levels. At 24 months postoperatively, 11 out of 12 patients reported good visual quality in the questionnaire. Conclusions: LBV surgery gradually achieves good binocular blended vision within 6 months postoperatively and demonstrates good safety, efficacy, and stability at 24 months. It maintains good functional vision and visual quality with high postoperative patient satisfaction.

Mass Measurement of Upper fp-Shell N=Z-2 and N=Z-1 Nuclei and the Importance of Three-Nucleon Force along the N=Z Line.

Using a novel method of isochronous mass spectrometry, the masses of ^{62}Ge, ^{64}As, ^{66}Se, and ^{70}Kr are measured for the first time, and the masses of ^{58}Zn, ^{61}Ga, ^{63}Ge, ^{65}As, ^{67}Se, ^{71}Kr, and ^{75}Sr are redetermined with improved accuracy. The new masses allow us to derive residual proton-neutron interactions (δV_{pn}) in the N=Z nuclei, which are found to decrease (increase) with increasing mass A for even-even (odd-odd) nuclei beyond Z=28. This bifurcation of δV_{pn} cannot be reproduced by the available mass models, nor is it consistent with expectations of a pseudo-SU(4) symmetry restoration in the fp shell. We performed ab initio calculations with a chiral three-nucleon force (3NF) included, which indicate the enhancement of the T=1 pn pairing over the T=0 pn pairing in this mass region, leading to the opposite evolving trends of δV_{pn} in even-even and odd-odd nuclei.

Sleep impairment in patients with empty nose syndrome.

BACKGROUND: Empty nose syndrome (ENS) is characterized by paradoxical nasal obstruction that usually occurs after turbinate surgery. Patients with ENS may also experience significant psychiatric symptoms and sleep dysfunction, which negatively affect the quality of life of affected subjects. This study aimed to evaluate sleep impairment and sleepiness in patients with ENS. METHODS: Patients with ENS and control participants were recruited prospectively. The Sino-Nasal Outcome Test-25 (SNOT-25), Empty Nose Syndrome 6-item Questionnaire (ENS6Q), Epworth Sleepiness Scale (EpSS), and modified sleep quality index (MSQI) were used to evaluate the participants before and after nasal surgery. RESULTS: Forty-eight patients with ENS and forty-eight age- and sex-matched control subjects were enrolled. The SNOT-25, ENS6Q, EpSS, and MSQI scores in the ENS group were all significantly higher than those in the control group before and after surgery. After surgery, ENS patients all exhibited significant improvements in SNOT-25, ENS6Q, EpSS, and MSQI scores. Regression analysis revealed that SNOT-25 score was a significant predictor of EpSS and MSQI in preoperative evaluations. ENS patients experiencing daytime sleepiness suffered from significantly more "dryness of nose" and "suffocation" than those not experiencing daytime sleepiness. CONCLUSIONS: Patients with ENS experienced significantly impaired sleep quality and sleepiness. Nasal reconstruction surgery improved the sleep quality of ENS patients. The severity of sleep dysfunction is associated with the severity of ENS symptoms. Recognizing individuals with significant sleep impairment and sleepiness and providing appropriate management are critical issues for ENS patients.

Disruptive Therapy Using a Nonsurgical Orthodontic Airway Plate for the Management of Neonatal Robin Sequence: 1-Year Follow-up.

We recently published the 3-month follow-up of 2 neonates with Robin sequence whose mandibular hypoplasia and restricted airway were successfully treated with an orthodontic airway plate (OAP) without surgical intervention. Both infants were successfully weaned off the OAP after several months of continuous use. We present the course of OAP treatment in these patients with a focus on breathing, feeding, and facial growth during their first year of life. Both infants demonstrated stable mandibular projection, resolution of obstructive sleep apnea, and normal development.

[Apatinib Suppressed Macrophage-Mediated Malignant Behavior of Hepatocellular Carcinoma Cells via Modulation of VEGFR2/STAT3/PD-L1 Signaling].

Hepatocellular carcinoma (HCC) is the most frequently diagnosed primary liver tumor worldwide. Tumor-associated macrophages (TAMs) usually have a similar phenotype to M2-like macrophages and can participate in tumor progression by secreting cytokines to suppress the immune response and activity of tumor-infiltrating lymphocytes. We investigated the role of M2 macrophages in HCC progression and explored the effects of vascular endothelial growth factor receptor 2 inhibitor-apatinib. As a cellular model of HCC, Hepb3 cell line was used. M2 macrophages were obtained by differentiation of THP-1 cells. The Transwell chamber was used to co-culture M2 macrophages and Hepb3 cells. CCK-8 and EdU assays were conducted to measure cell viability and proliferation capacity. Transwell migration assay was performed to estimate cellular metastatic potential. Cytokine expression levels were assessed by ELISA. Western blotting was used to characterize activation of the VEGFR2/STAT3/PD-L1 axis. It has been shown that co-culture with M2 macrophages increased viability, cytokine production, promoted proliferation, invasion, and migration of Hepb3 cells. The secretion of TGF-ß1, IL-6, MMP-9, and VEGF was significantly increased after co-culture. In contrast apatinib suppressed M2 macrophage-induced proliferation, cell viability, invasion, and migration of Hepb3 cells. Moreover, apatinib markedly decreased expression levels of p-VEGFR2, p-STAT3, and PD-L1 in Hepb3 cells under the co-culture conditions. In conclusion, apatinib treatment can suppress TAMs-mediated malignant behavior of HCC cells via modulation of the VEGFR2/STAT3/PD-L1 signaling pathway.

[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.

[Correlation between serum autotaxin level and pulmonary ultrasound score with the disease severity and 28-day mortality in patients with acute respiratory disease syndrome].

Objective: To investigate the relationship between serum autocrine motor factor (Autotaxin) level and pulmonary ultrasound score (LUS) and the disease severity and 28-day mortality of patients with acute respiratory distress syndrome (ARDS). Methods: Totally 142 ARDS patients admitted to Danzhou People's Hospital from January 2019 to December 2021 were selected, and serum Autotaxin level and LUS score of ARDS patients on the day of onset were detected. According to the survival within 28 days after entering the intensive care unit, ARDS patients were divided into survival group (86 cases) and death group (56 cases). According to the oxygenation index, ARDS patients were divided into mild group (200 mmHg

First Application of Mass Measurements with the Rare-RI Ring Reveals the Solar r-Process Abundance Trend at A=122 and A=123.

The Rare-RI Ring (R3) is a recently commissioned cyclotronlike storage ring mass spectrometer dedicated to mass measurements of exotic nuclei far from stability at Radioactive Isotope Beam Factory (RIBF) in RIKEN. The first application of mass measurement using the R3 mass spectrometer at RIBF is reported. Rare isotopes produced at RIBF-^{127}Sn, ^{126}In, ^{125}Cd, ^{124}Ag, ^{123}Pd-were injected in R3. Masses of ^{126}In, ^{125}Cd, and ^{123}Pd were measured whereby the mass uncertainty of ^{123}Pd was improved. This is the first reported measurement with a new storage ring mass spectrometry technique realized at a heavy-ion cyclotron and employing individual injection of the preidentified rare nuclei. The latter is essential for the future mass measurements of the rarest isotopes produced at RIBF. The impact of the new ^{123}Pd result on the solar r-process abundances in a neutron star merger event is investigated by performing reaction network calculations of 20 trajectories with varying electron fraction Y_{e}. It is found that the neutron capture cross section on ^{123}Pd increases by a factor of 2.2 and ß-delayed neutron emission probability, P_{1 n}, of ^{123}Rh increases by 14%. The neutron capture cross section on ^{122}Pd decreases by a factor of 2.6 leading to pileup of material at A=122, thus reproducing the trend of the solar r-process abundances. The trend of the two-neutron separation energies (S_{2n}) was investigated for the Pd isotopic chain. The new mass measurement with improved uncertainty excludes large changes of the S_{2n} value at N=77. Such large increase of the S_{2n} values before N=82 was proposed as an alternative to the quenching of the N=82 shell gap to reproduce r-process abundances in the mass region of A=112-124.

Nonsurgical Orthodontic Airway Plate Treatment for Newborns With Robin Sequence.

Despite promising outcomes for >50 years, nonsurgical orthodontic airway plates (OAP) are only infrequently offered for babies with Robin sequence in a few parts of the world. This article demonstrates possibility of providing functional improvement using an OAP to help these babies overcome their functional and structural difficulties on their own. Two consecutively treated cases are presented exemplifying that OAP treatment that had originated from Europe is reproducible and effective in an institution in the United States.

[Efficacy of total oral regimens containing ixazomib in patients with relapsed and refractory multiple myeloma].

To investigate the efficacy and safety of total oral regimen containing ixazomib in multidrug-resistant relapsed and refractory multiple myeloma(RRMM). A total of 38 patients were retrospectively analyzed from August 2018 to January 2020 in the First Affiliated Hospital of Soochow University. The overall response rate (ORR)was 36.8%. Among them, the very good partial response (VGPR) or better rate was 23.7%, and the complete response (CR) rate was 5.3%. The ORR was 41.7% in patients receiving ixazomib-lenalidomide-dexamethasone (IRD) regimen. Median PFS was 5 months and median OS was 7.5 months. The ORR was 50% after second-line therapy, 40% after third-line therapy and 12.5% after forth-line therapy or more. The ORR was 29.0% in bortezomib-refractory patients, 38.0% in lenalidomide-refractory patients, 21.4% in bortezmoib & lenalidomide dual refractory patients. Grade 3-4 hematological adverse events (AEs) were reported in 21% patients. Common hematological AEs included lymphopenia, neutropenia, thrombocytopenia. Other usual AEs were fatigue and diarrhea. No grade 3-4 peripheral neuropathy was recorded. In the treatment of relapsed/refractory multiple myeloma patients with multidrug resistance, the total oral regimens containing ixazomib demonstrate reliable efficacy and safety. Early administration of ixazomib at first or second relapse is suggested for more favorable clinical outcome.

[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.

[Research progress on the incidence and economic burden of herpes zoster disease in immunocompromised population].

With the increase of age or the impairment of immune function, the specific cellular immune level against varicella zoster virus (VZV) in the body decreases, and the latent VZV in the ganglion can be reactivated to cause herpes zoster (HZ). HZ and its main complication postherpetic neuralgia (PHN) can seriously affect the quality of life of patients. The immunocompromised (IC) population is more prone to HZ than the immunocompetent population due to diseases and therapeutic drugs. This paper reviews the incidence, risk factor and economic burden of HZ in IC population with special health status, to provide ideas for research and adjustment of immunization strategies in the future.

[Temporal trend of antibiotic use among primary school children in Shanghai, 2017-2020].

To investigate the temporal trend of antibiotic use among children in Shanghai from 2017 to 2020. The stratified cluster sampling method was used to establish a dynamic cohort of healthy children based on primary schools in Changning District, Shanghai. In the cohort, there were 282 children from 2017, 287 children from 2018, 294 from 2019 and 301 from 2020. A total of 700 children aged 7-11 years were included in the study. The basic information and antibiotic use of children were investigated by questionnaire every year, and their height and weight were measured at the same time. Chi-square test was used to analyze the difference of antibiotic use rate in each year and generalized estimation equation was used to analyze the temporal trend of antibiotic use. The results showed that the use rates of all antibiotics, cephalosporins, azithromycin and other antibiotics (including penicillin, lincomycin, quinolones, etc.) of children between 2017 and 2020 were 15.6%, 10.5%, 2.7%, and 2.4%, respectively. In 2017, 2018, 2019, and 2020, there were significant differences for the use rates of total antibiotics and other antibiotics in children (P=0.033, P=0.040), and there were no significant differences for the use rates of cephalosporins and azithromycin (P=0.274, P=0.455). After adjusting for children's basic characteristics, the generalized estimation equation showed that the annual use rate of all antibiotics, cephalosporins, and other antibiotics decreased over time.

[Gene expression signature analysis of peripheral blood mononuclear cells from patients with for high altitude pulmonary hypertension and value for potential drug selection].

Objective: To investigate the gene expression characteristics of peripheral blood mononuclear cells from patients with high altitude pulmonary hypertension (HAPH) in Naxi residents living in Lijiang, Yunnan, and to explore the underlying pathogenesis and value for potential drug selection. Methods: This is a case-control study. Six patients with HPAH (HPAH group) and 4 normal subjects (control group) were selected from the Naxi residents who originally lived in Lijiang, Yunnan Province. The general clinical data of the two groups were collected, and the related indexes of pulmonary artery pressure were collected. Peripheral blood mononuclear cells of the subjects were collected for RNA sequencing. The differences on gene expression, regulatory network of transcription factors and drug similarity between the two groups were compared. The results were compared with the public data of idiopathic pulmonary arterial hypertension (IPAH). Biological processes and signal pathways were analyzed and compared between HPAH and IPAH patients. Results: The age of 6 patients with HAPH was (68.1±8.3) years old, and there were 2 males (2/6). The age of 4 subjects in the control group was (62.3±10.9) years old, and there were 2 males (2/4). Tricuspid regurgitation velocity, tricuspid pressure gradient and pulmonary systolic pressure in HAPH group were significantly higher than those in control group (all P<0.05). The results of RNA sequencing showed that compared with the control group, 174 genes were significantly upregulated and 169 genes were downregulated in peripheral blood mononuclear cells of HAPH group. These differentially expressed genes were associated with 220 biological processes, 52 molecular functions and 23 cell components. A total of 21 biological processes and 2 signal pathways differed between HPAH and IPAH groups, most of which were related to inflammation and immune response. ZNF384, SP1 and STAT3 were selected as highly correlated transcription factors by transcription factor prediction analysis. Trichostatin A and vorinostat were screened out as potential drugs for the treatment of HAPH by drug similarity analysis. Conclusions: There are significant differences in gene expression in peripheral blood monocytes between HAPH patients and normal population, and inflammation and immune dysfunction are the main pathogenic factors. Trichostatin A and Vorinostat are potential drugs for the treatment of HAPH.

Identification and iterative combinatorial mutagenesis of a new naringinase-producing strain, Aspergillus tubingensis MN589840.

Naringinase was mainly obtained by microbial fermentation, and mutagenesis was a major way for obtaining excellent mutants. The aim of this study was to screen out a high naringinase yielding mutant to enhance the potential application value of its industrialization and compare the effects of different mutagenic methods on the enzyme activity of the strain. A novel producing naringinase strain, Aspergillus tubingensis MN589840, was isolated from mildewed pomelo peel, later subjected to mutagenesis including UV, ARTP and UV-ARTP. After five rounds iterative mutagenesis, the mutants U1, A6 and UA13 were screened out with 1448·49, 1848·71, 2475·16 U mg-1 enzyme activity, the naringinase productivity raised by 79·08, 123·56 and 206%, respectively. In addition, the naringinase activity of three mutants rose after each round of iterative mutagenesis. These results indicated that the mutagenesis efficiency of UV-ARTP was higher than that of single ARTP, and both are better than UV. In summary, the iterative UV-ARTP mutagenesis is an effective strategy for screening high naringinase-producing strains.

Metabolic syndrome cannot mask the changes of faecal microbiota compositions caused by primary hepatocellular carcinoma.

Both hepatocellular carcinoma (HCC) and metabolic syndrome are closely associated with the composition of the gut microbiota (GM). Although it has been proposed that elements of the GM can be used as biomarkers for the early diagnosis of HCC, whether metabolic syndrome results in a misrepresentation of the results of the early diagnosis of HCC using GM remains unclear. We compared the differences in the faecal microbiota of 10 patients with primary HCC, six patients with type 2 diabetes mellitus (T2DM), seven patients with arterial hypertension, six patients with both HCC and T2DM, and 10 patients with both HCC and arterial hypertension, as well as 10 healthy subjects, using high-throughput sequencing of 16S rRNA gene amplicons. Our results revealed a significant difference in the GM between subjects with and without HCC. The 49 bacterial genera out of the 494 detected genera were significantly different between the groups. These results show that changes in the GM can be used to distinguish between subjects with and without HCC, and can resist interference of T2DM and arterial hypertension with the GM. The results of the present study provide an important basis for the clinical auxiliary diagnosis of HCC by detecting the GM.