Open-label, dose-escalation FIGHT-101 study of pemigatinib combined with targeted therapy, chemotherapy, or immunotherapy in patients with advanced malignancies.

BACKGROUND: Pemigatinib is an oral, potent, selective fibroblast growth factor receptor (FGFR) 1-3 inhibitor. FIGHT-101, a three-part, open-label, first-in-human, phase I/II study (NCT02393248), evaluated pemigatinib in patients with advanced solid tumors. In parts 1 and 2, pemigatinib monotherapy had a manageable safety profile and antitumor activity in FGFR-altered tumors. Part 3 (pemigatinib combination therapies) results are presented here. PATIENTS AND METHODS: Patients received 9, 13.5, or 20 mg oral once-daily pemigatinib on continuous or intermittent schedules with gemcitabine and cisplatin (pemi/gem/cis), docetaxel (pemi/doc), trastuzumab (pemi/tras), pembrolizumab (pemi/pembro), or retifanlimab (pemi/reti) irrespective of whether the tumor was confirmed as FGFR altered. Primary endpoints were safety and pharmacodynamics. Secondary endpoints were investigator-assessed tumor objective response rates (ORRs) and pharmacokinetics (PK). RESULTS: Of 65 enrolled patients (pemi/gem/cis, n = 8; pemi/doc, n = 7; pemi/tras, n = 6; pemi/pembro, n = 26; pemi/reti, n = 18), all discontinued. Treatment-emergent adverse events (TEAEs) were generally consistent with individual drug AEs. Serious and grade ≥3 TEAEs occurred in 0%-85.7% and 33.3%-100.0% of patients across treatment groups, respectively. All pemigatinib combinations demonstrated steady-state PK comparable to monotherapy. Pharmacodynamic effects in all pemigatinib combinations, except pemi/gem/cis, were consistent with monotherapy. Less inhibition of FGFR2α phosphorylation was observed with this combination. ORRs (95% confidence interval) were 37.5% [8.5% to 75.5% (pemi/gem/cis)], 14.3% [0.4% to 57.9% (pemi/doc)], 0% (pemi/tras), 26.9% [11.6% to 47.8% (pemi/pembro)], and 11.1% [1.4% to 34.7% (pemi/reti)]. All groups had instances of tumor shrinkage. ORRs in assessable patients with FGFR rearrangements and mutations were 50% and 33%, respectively. CONCLUSIONS: Pemigatinib combination therapy showed no unexpected toxicities. PK and pharmacodynamics were mostly consistent with pemigatinib monotherapy. Pemi/gem/cis (37.5%) and pemi/pembro (26.9%) had the highest ORR; most responders had FGFR alterations.

[Multicenter evaluation of minimal residual disease monitoring in early induction therapy for treatment of childhood acute lymphoblastic leukemia].

Objective: To evaluate the role of minimal residual disease (MRD) monitoring during early induction therapy for the treatment of childhood acute lymphoblastic leukemia (ALL). Methods: This was a multicenter retrospective cohort study. Clinical data of 1 164 ALL patients first diagnosed between October 2016 and June 2019 was collected from 16 hospitals in South China Children's Leukemia Group. According to MRD assay on day 15 of early induction therapy, they were divided into MRD<0.10% group, MRD 0.10%-<10.00% group and MRD≥10.00% group. According to MRD assay on day 33, they were divided into MRD<0.01% group, MRD 0.01%-<1.00% group and MRD≥1.00% group. Age, onset white blood cell count, central nervous system leukemia (CNSL), molecular genetic characteristics and other data were compared between groups. Kaplan-Meier method was used for survival analysis. Cox regression model was used to analyze prognostic factors. Results: Of the 1 164 enrolled patients, there were 692 males and 472 females. The age of diagnosis was 4.7 (0.5, 17.4) years. The white blood cell count at initial diagnosis was 10.7 (0.4, 1 409.0) ×109/L. Among all patients, 53 cases (4.6%) had CNSL. The follow-up time was 47.6 (0.5, 68.8) months. The 5-year overall survival (OS) and 5-year relapse-free survival (RFS) rates were (93.1±0.8) % and (90.3±1.1) %. On day 15 of early induction therapy, there were 466 cases in the MRD<0.10% group, 523 cases in the MRD 0.10%-<10.00% group and 175 cases in the MRD≥10.00% group. The 5-year OS rates of the MRD<0.10% group, MRD 0.10%-<10.00% group and MRD≥10.00% group were (95.4±1.0) %, (93.3±1.1) %, (85.4±2.9) %, respectively, while the RFS rates were (93.2±1.6) %, (90.8±1.4) %, (78.9±4.3) %, respectively (χ2=16.47, 21.06, both P<0.05). On day 33 of early induction therapy, there were 925 cases in the MRD <0.01% group, 164 cases in the MRD 0.01%-<1.00% group and 59 cases in the MRD≥1.00% group. The 5-year RFS rates in the MRD 0.01%-<1.00% group was lowest among three groups ((91.4±1.2) % vs. (84.5±3.2) % vs. (87.9±5.1) %). The difference between three groups is statistically significant (χ2=9.11, P=0.010). Among ALL patients with MRD≥10.00% on day 15 of induction therapy, there were 80 cases in the MRD <0.01% group on day 33, 45 cases in the MRD 0.01%-<1.00% group on day 33 and 45 cases in the MRD≥1.00% group on day 33. The 5-year RFS rates of three groups were (83.9±6.0)%, (67.1±8.2)%, (83.3±6.9)% respectively (χ2=6.90, P=0.032). Univariate analysis was performed in the MRD≥10.00% group on day 15 and the MRD 0.01%-<1.00% group on day 33.The 5-year RFS rate of children with CNSL was significantly lower than that without CNSL in the MRD≥10.00% group on day 15 ((50.0±20.4)% vs. (80.3±4.4)%,χ2=4.13,P=0.042). Patients with CNSL or MLL gene rearrangement in the MRD 0.01%-<1.00% group on day 33 had significant lower 5-year RFS rate compared to those without CNSL or MLL gene rearrangement ((50.0±25.0)% vs. (85.5±3.1)%,χ2=4.06,P=0.044;(58.3±18.6)% vs. (85.7±3.2)%,χ2=9.44,P=0.002). Multivariate analysis showed that age (OR=0.58, 95%CI 0.35-0.97) and white blood cell count at first diagnosis (OR=0.43, 95%CI 0.27-0.70) were independent risk factors for OS. The MRD level on day 15 (OR=0.55,95%CI 0.31-0.97), ETV6-RUNX1 fusion gene (OR=0.13,95%CI 0.03-0.54), MLL gene rearrangement (OR=2.55,95%CI 1.18-5.53) and white blood cell count at initial diagnosis (OR=0.52,95%CI 0.33-0.81) were independent prognostic factors for RFS. Conclusions: The higher the level of MRD in early induction therapy, the worse the OS. The MRD levels on day 15 is an independent prognostic factor for RFS.The MRD in early induction therapy guided accurate risk stratification and individualized treatment can improve the survival rate of pediatric ALL.

A first-in-human phase I study of the PD-1 inhibitor, retifanlimab (INCMGA00012), in patients with advanced solid tumors (POD1UM-101).

BACKGROUND: Retifanlimab is a humanized, hinge-stabilized immunoglobulin G4κ monoclonal antibody against human programmed cell death protein 1 (PD-1). This first-in-human, phase I study assessed the safety and efficacy of retifanlimab in patients with advanced solid tumors and identified optimal dosing. PATIENTS AND METHODS: POD1UM-101 was conducted in two parts: (i) dose escalation-evaluated retifanlimab [1 mg/kg every 2 weeks (q2w), 3 or 10 mg/kg q2w or every 4 weeks (q4w)] in patients with relapsed/refractory, unresectable, locally advanced or metastatic solid tumors; (ii) cohort expansion-biomarker-unselected tumor-specific cohorts [endometrial, cervical, sarcoma, non-small-cell lung cancer (NSCLC)] received retifanlimab 3 mg/kg q2w, and tumor-agnostic cohorts received flat dosing [375 mg every 3 weeks (q3w), or 500 and 750 mg q4w]. Primary objectives were safety and tolerability; secondary objective was efficacy in selected tumor types. RESULTS: Thirty-seven patients were enrolled in dose escalation, 134 in PD-1 therapy-naïve tumor-specific cohort expansion (endometrial, n = 29; cervical, NSCLC, soft tissue sarcoma, each n = 35), and 45 in flat dosing (375 mg q3w, 500 and 750 mg q4w, each n = 15). No dose-limiting toxicities occurred during dose escalation; maximum tolerated dose was not reached and 3-mg/kg q2w expansion dose was selected based on safety and pharmacokinetic data. Immune-related adverse events were experienced by 40 patients (30%) in tumor-specific cohorts (most frequently hypothyroidism, hyperthyroidism, colitis, nephritis) and 6 (13%) in flat dosing (most frequently hypothyroidism, hyperthyroidism). Objective response rate (95% confidence interval) was 14% (4.8 to 30.3), 14% (3.9 to 31.7), 20% (8.4 to 36.9), and 3% (0.1 to 14.9) in advanced NSCLC, endometrial, cervical, and sarcoma tumor-specific cohorts that progressed after multiple prior systemic therapies. CONCLUSIONS: Retifanlimab demonstrated clinical pharmacology, safety, and antitumor activity consistent with the programmed death (ligand)-1 inhibitor class. POD1UM-101 results support further exploration of retifanlimab as monotherapy and backbone immunotherapy in combination treatments, with recommended doses of 500 mg q4w and 375 mg q3w.

[Analysis of distribution characteristics and influencing factors of chord µ in young myopia].

Objective: To explore and analyze the distribution characteristics of chord µ related parameters, as well as the pupil center's relative position to the coaxial corneal light reflex on the corneal surface, and the influencing factors in young myopia. Methods: This was a cross-sectional study. A total of 761 myopic patients (761 eyes) were collected from March 2021 to December 2021 in the Refractive Surgery Center of Tianjin Eye Hospital, including 388 males and 373 females, with an average age of (24±6) years. The relationship between age, sex, diopter, anterior and posterior corneal surface parameters, and chord µ related parameters was analyzed, including the x and y absolute values of the pupil center, chord µ length, and angle. The normality of the data was tested using the Kolmogorov-Smirnov test, and the influencing factors of chord µ were analyzed through Pearson and Spearman correlation analysis. Results: The equivalent spherical degree and chord µ length were (-5.47±1.66) D and (0.178±0.095) mm, respectively. The chord µ length followed an approximately normal distribution. The chord µ length of 266 eyes (35%) was distributed in the range of 0.120 to 0.200 mm, while the chord µ length of 479 eyes (63%) was<0.200 mm, and the chord µ length of 620 eyes (81%) was<0.260 mm. The chord µ angle distribution accounted for the largest proportion in the superior nasal quadrant (45.6%), followed by the superior temporal quadrant (34.3%), the inferior temporal quadrant (10.1%), and the inferior nasal quadrant (10.0%). High myopia (r=0.11, P=0.002) and high astigmatism (r=0.08, P=0.023) were associated with an increase in chord µ length. The higher the degree of myopia, the smaller the chord µ angle (r=-0.09, P=0.019). The larger the ISV (r=0.09, P=0.017), IVA (r=0.08, P=0.025), and IHD (r=0.08, P=0.039) on the anterior surface of the cornea, the longer the chord µ length. The higher the astigmatism of the posterior corneal surface, the greater the absolute value of the Y coordinate of the pupil center (r=0.07, P=0.044), and the longer the chord µ length (r=0.08, P=0.035), and the smaller the chord µ angle (r=-0.08, P=0.032). Conclusions: The chord µ length of young myopic individuals in China followed an approximately normal distribution, with the majority located in the superior nasal and superior temporal quadrants. High myopia, high astigmatism, and irregular corneal shape are the main factors related to an increase in chord µ length.

[Effects of the anterolateral thigh chimeric perforator flaps in repairing complex wounds of foot and ankle].

Objective: To investigate the effects of anterolateral thigh chimeric perforator flap in repairing complex wounds of foot and ankle. Methods: A retrospective observational study was conducted. From May 2018 to June 2022, 23 patients who met the inclusion criteria were admitted to the First Affiliated Hospital of Air Force Medical University to repair complex wounds of foot and ankle with anterolateral thigh chimeric perforator flaps, including 15 males and 8 females, aged from 20 to 66 years. The wounds were all accompanied by bone exposure and defects, and were complicated with varying degrees of infection. All patients underwent debridement and continuous vacuum sealing drainage treatment for 1 week in stage Ⅰ, with the skin and soft tissue defect area after debridement being 10 cm×5 cm to 22 cm×7 cm. In stage Ⅱ, the anterolateral thigh chimeric perforator flap was used to cover the defective wound, of which the muscle flap was used to fill the deep invalid cavity of the ankle joint or cover bone and internal fixation exposures, and the skin flap was used to cover the superficial wound, with the area of the skin flap ranging from 11 cm×6 cm to 23 cm×8 cm, and the area of the muscle flap ranging from 4.0 cm×2.5 cm to 8.0 cm×5.0 cm. The survival of the flap was observed after operation. During follow-up, the color, texture, appearance, and complications of the flap were observed, the function of ankle joint and its range of dorsiflexion motion and plantar flexion motion were measured, and the scar hyperplasia and muscular hernia in donor area were observed. Results: Ecchymosis and epidermal necrosis occurred at the tip of the flap in 1 patient on 5 days after operation and healed after dressing change for 1 week; the other flaps of patients survived successfully. After 6 to 40 months of follow-up, the color, texture, and shape of flaps were good, but 1 patient was not satisfied with the shape of the flap because of flap swelling; the ankle joint movement was basically normal, the dorsiflexion motion was 15-30°, and the plantar flexion motion was 20-45°; the scar hyperplasia in the donor area of the flap was not obvious, and no muscular hernia occurred. Conclusions: The anterolateral thigh chimeric perforator flap can effectively fill the deep invalid cavity of ankle joint and cover the superficial wound at the same time, with minimal damage to the donor site. So it is an ideal flap for repairing the complex wounds of foot and ankle.

Ti-doped iron phosphide nanoarrays grown on carbon cloth as a self-supported electrode for enhanced electrocatalytic nitrogen reduction.

The electrocatalytic nitrogen reduction reaction (eNRR) has been widely recognized as a promising method for green ammonia synthesis. However, the inert NN bond, inferior catalytic activity and small electrochemically active area impede its practical application. To circumvent these problems, we proposed self-supported Ti-doped iron phosphide (FeP) nanorod arrays grown on carbon cloth (Ti-FeP/CC) as an electrode for eNRR. The introduction of Ti doping sites regulated the electron structure of FeP, leading to electron migration from Fe to P, which facilitated N2-to-NH3 conversion. The as-prepared Ti-FeP/CC showed an enhancement of electrochemical surface area (ECSA), high electrical conductivity and well-exposed active sites. Ti-FeP/CC was capable of producing a high NH3 yield of 10.93 µg h-1 cm-2 and faradaic efficiency of 10.77% at an optimal voltage of -0.3 V (vs. RHE) in a 0.1 M Na2SO4 solution with excellent stability and durability during the eNRR process. This work not only presents a promising electrode material for eNRR, but also provides a new insight into rational heteroatom doping for electrocatalysis.

Hierarchical Ni-Mn LDHs@CuC2O4 Nanosheet Arrays-Modified Copper Mesh: A Dual-Functional Material for Enhancing Oil/Water Separation and Supercapacitors.

The pursuit of superhydrophilic materials with hierarchical structures has garnered significant attention across diverse application domains. In this study, we have successfully crafted Ni-Mn LDHs@CuC2O4 nanosheet arrays on a copper mesh (CM) through a synergistic process involving chemical oxidation and hydrothermal deposition. Initially, CuC2O4 nanosheets were synthesized on the copper mesh, closely followed by the growth of Ni-Mn LDHs nanosheets, culminating in the establishment of a multi-tiered surface architecture with exceptional superhydrophilicity and remarkable underwater superoleophobicity. The resultant Ni-Mn LDHs@CuC2O4 CM membrane showcased an unparalleled amalgamation of traits, including superhydrophilicity, underwater superoleophobicity, and the ability to harness photocatalytic forces for self-cleaning actions, making it an advanced oil-water separation membrane. The membrane's performance was impressive, manifesting in a remarkable water flux range (70 kL·m-2·h-1) and an efficient oil separation capability for both oil/water mixture and surfactant-stabilized emulsions (below 60 ppm). Moreover, the innate superhydrophilic characteristics of the membrane rendered it a prime candidate for deployment as a supercapacitor cathode material. Evidenced by a capacitance of 5080 mF·cm-2 at a current density of 6 mA cm-2 in a 6 M KOH electrolyte, the membrane's potential extended beyond oil-water separation. This work not only introduces a cutting-edge oil-water separation membrane and supercapacitor electrode but also offers a promising blueprint for the deliberate engineering of hierarchical structure arrays to cater to a spectrum of related applications.

[Clinical characteristics of 7 cases of hepatic portal venous gas].

OBJECTIVE: To summarize and analyze the clinical characteristics of patients diagnosed with hepatic portal venous gas (HPVG). METHODS: This was a single center retrospective observational study. All of the patients were diagnosed with HPVG. The patients were admitted to Peking University Third Hospital from January 2017 to January 2021. Demographic characteristics, clinical manifestations, laboratory tests, abdominal imaging, treatment of the primary disease, and clinical outcomes of the patients were collected via electronic medical records. The study was approved by institutional review board and the information of all the patients was kept de-identified. RESULTS: A total of seven cases were included in the study. The median age of the patients was 67 (63, 81) years. Six of the patients were male. The seven patients all presented with sudden onset of severe abdominal pain, which was the most common symptom. Six patients developed septic shock after admission. The signs of HPVG were detected by CT scans in all the patients, showing gas embolization. It might also be found as unique "aquarium sign" in abdominal ultrosonography. Four cases were caused by intestinal lesions, including acute volvulus, intestinal obstruction, and rectal abscess. Two were caused by ischemic bowel disease and the other one was caused by severe acute pancreatitis. The gas accumulation could disappear after effective anti-shock therapy and surgery (Cases 1, 2, and 6). Two patients had good postoperative outcomes, and one patient was discharged after non-surgical treatment. However, the prognosis was poor in the patients with intestinal ischemia necrosis accompanied by shock and multiple organ dysfunction (Cases 3, 4, 5, and 7 all died). CONCLUSION: The HPVG patients generally have acute abdominal pain and show up at Emergency Department. The prognosis depends on the potential cause of HPVG. The mechanism and clinical management for the appearance of gas in the portal vein is not well understood. Patients complicated with shock, ascites, and peritonitis may have intestinal necrosis, which indicates surgical intervention and higher mortality. CT is the preferred diagnostic method in standard clinical practice. Physicians need to have a comprehensive understanding of the proactive diagnostic strategy, and active treatment for the primary disease.

A randomized trial of eribulin monotherapy versus eribulin plus anlotinib in patients with locally recurrent or metastatic breast cancer.

BACKGROUND: Eribulin mesylate is a novel, nontaxane, microtubule dynamics inhibitor. In this study, we assessed the efficacy and safety of eribulin versus eribulin plus the oral small-molecule tyrosine kinase inhibitor anlotinib in patients with locally recurrent or metastatic breast cancer. PATIENTS AND METHODS: In this single-center, open-label, phase II clinical study (NCT05206656) conducted in a Chinese hospital, patients with human epidermal growth factor receptor 2 (HER2)-negative, locally recurrent or metastatic breast cancer previously treated with anthracycline- or taxane-based chemotherapy were randomized (1 : 1) to receive eribulin alone or in combination with anlotinib. The primary efficacy endpoint was investigator-assessed progression-free survival (PFS). RESULTS: From June 2020 to April 2022, a total of 80 patients were randomly assigned to either eribulin monotherapy or eribulin plus anlotinib combination therapy, with 40 patients in each group. The data cut-off was 10 August 2022. The median PFS was 3.5 months [95% confidence interval (CI) 2.8-5.5 months] for eribulin and 5.1 months (95% CI 4.5-6.9 months) for eribulin plus anlotinib (hazard ratio = 0.56, 95% CI 0.32-0.98; P = 0.04). The objective response rates were 32.5% versus 52.5% (P = 0.07), respectively, and disease control rates were 67.5% versus 92.5% (P = 0.01), respectively. Patients <50 years of age, with an Eastern Cooperative Oncology Group performance status score of 0, visceral metastasis, number of treatment lines of four or more, hormone receptor negative (triple-negative), and HER2 low expression appeared to benefit more from combined treatment. The most common adverse events in both groups were leukopenia (n = 28, 70.0%, patients in the eribulin monotherapy group versus n = 35, 87.5%, patients in the combination therapy group), aspartate aminotransferase elevations (n = 28, 70.0%, versus n = 35, 87.5%), neutropenia (n = 25, 62.5%, versus n = 31, 77.5%), and alanine aminotransferase elevations (n = 25, 62.5%, versus n = 30, 75.0%). CONCLUSION: Eribulin plus anlotinib can be considered an alternative treatment option for HER2-negative locally advanced or metastatic breast cancer.

[Effect of Friday surgery on clinical outcome of elderly patients with hip fracture under multidisciplinary treatment].

Objective: To assess the impact of Friday surgery on clinical outcomes in elderly patients with hip fracture under multidisciplinary treatment. Methods: A retrospective cohort study. The clinical data of 414 geriatric patients with hip fractures admitted to Zhongda Hospital Affiliated with Southeast University from January 2018 to March 2021 were analyzed retrospectively, including 126 males and 288 females with a mean age of (81.3±7.6) years. The patients were divided into two groups based on whether they underwent surgery on Friday or not. The Friday group(n=69) and the non-Friday group(n=345) were compared in terms of general information, American Society of Anesthesiologists(ASA) classification, fracture type, injury to admission time, preoperative waiting time, surgical method, anesthesia type and use of intensive care unit (ICU) fast track. Propensity score matching (PSM) was performed based on age, ASA grade, time from injury to admission, preoperative waiting time, hemoglobin and albumin levels at admission. Clinical outcomes were collected and compared between the two groups, including length of hospital stay, total hospitalization cost and 30-day, 90-day and 1-year mortality rates, and postoperative complications. Multivariate logistic regression analyses were conducted to identify influencing factors for 1-year mortality in geriatric patients with hip fracture. Results: Baseline data showed statistically significant differences in hemoglobin, albumin and preoperative waiting time between the two groups (all P<0.05). After PSM matching, 69 patients were included in each group, and no significant differences were observed in baseline data between the two groups (all P>0.05). There was no significant differences in 30-day mortality rate (4.3% vs 0, P=0.080), 90-day mortality rate (7.2% vs 1.4%, P=0.095), length of hospital stay [(10.85±4.45)d vs (10.92±3.68)d, P=0.919], total hospitalization cost [(60.9±15.4) thousands yuan vs (59.1±15.4) thousands yuan, P=0.489], postoperative complications [pneumonia (11.6% vs 13.0%, P=0.796), cardio-cerebrovascular complications (11.6% vs 8.7%, P=0.573) and delirium (5.7% vs 2.9%, P=0.245)] between the Friday group and the non-Friday group (all P>0.05). However, the 1-year mortality rate was higher in the Friday group than that in the non-Friday group(18.8% vs 4.3%, P=0.008). Multivariate analysis revealed that surgery on Friday (OR=11.222, 95%CI: 2.198-57.291, P=0.004), low hemoglobin levels at admission (OR=0.920, 95%CI: 0.875-0.967, P=0.001), hemiarthroplasty treatment (OR=5.127, 95%CI: 1.308-20.095, P=0.019) and longer surgery duration (OR=0.958, 95%CI: 0.927-0.989, P=0.009) were influencing factors for 1-year mortality in geriatric patients with hip fracture. Conclusions: In the context of multidisciplinary treatment, Friday surgery does not increase short-term mortality, length of hospital stay, total hospitalization cost or incidence of complications in geriatric patients with hip fracture. However, it remains a influencing factor for 1-year mortality in those patients.

Clinical outcomes of intra-arterial chemotherapy combined with iodine-125 seed brachytherapy in the treatment of malignant superior vena cava syndrome caused by small cell lung cancer.

PURPOSE: Currently there is a lack of effective treatment strategies for malignant superior vena cava syndrome (SVCS). We aim to investigate the therapeutic effect of intra-arterial chemotherapy (IAC) combined with the Single Needle Cone Puncture method for the 125I brachytherapy (SNCP-125I) in treating SVCS caused by stage III/IV Small Cell Lung Cancer (SCLC). MATERIALS AND METHODS: Sixty-two patients with SCLC who developed SVCS from January 2014 to October 2020 were investigated in this study. Out of these 62 patients, 32 underwent IAC combined with SNCP-125I (Group A) and 30 patients received IAC treatment only (Group B). Clinical symptom remission, response rate, disease control rate, and overall survival of these two groups of patients were analyzed and compared. RESULTS: The remission rate of symptoms including dyspnea, edema, dysphagia, pectoralgia, and cough of malignant SVCS in Group A was significantly higher than that in Group B (70.5 and 50.53%, P=0.0004, respectively). The disease control rates (DCR, PR+CR+SD) of Group A and B were 87.5 and 66.7%, respectively (P=0.049). Response rates (RR, PR+CR) of Group A and Group B were 71.9 and 40% (P=0.011). The median overall survival (OS) of Group A was significantly longer than that in Group B which was 18 months compared to 11.75 months (P=0.0360). CONCLUSIONS: IAC treatment effectively treated malignant SVCS in advanced SCLC patients. IAC combined with SNCP-125I in the treatment of malignant SVCS caused by SCLC showed improved clinical outcomes including symptom remission and local tumor control rates than IAC treatment only in treating SCLC-induced malignant SVCS.

Efficient photo-adsorptive eradication of endocrine disrupting pesticides by chitosan co- decorated metal oxide bio-nanocomposite.

Extensive consumption, toxicity and bioaccumulation of malathion (MLT) and lindane (γ-HCH) pesticides collectively attract the world's attention. Herein, the nanocomposite of chitosan wrapped NiO@ZnO was synthesized by a green methodology using Azadirachta indica leaves extract. Structural and morphological analysis of chitosan-NiO@ZnO showed hollow sphere-flake shaped image adsorbed on a solid chitosan surface with a large surface area of 73 m2g-1. A decrease in values of lattice strain, dislocation density and crystallite size described the imperfection in crystal geometry and new peaks in FT-IR spectra at 698 cm-1 and 448 cm-1 of Ni-N and Zn-N, which respectively confirm the coupling. Chitosan-NiO@ZnO and individual nanoparticles (NiO and ZnO) were well-characterized and utilized for degradation MLT and γ-HCH under direct sunlight and dark conditions. The highest degradation of pesticides (above 94%) resulted with 2 mg L-1 and 10 mg L-1 of MLT (π-π) and γ-HCH, respectively with a 20 mg catalyst dose, and pH of ~ 7 under daylight exposure (5 h). Chitosan-NiO@ZnO substantially suppressed the half-life of the targeted pesticides (MLT: 0.48 h; HCH 0.51 h) and demonstrated the first-order kinetics with a high adsorption capacity, Xm (MLT: 14.5 mg g-1 and γ-HCH 20.7 mg g-1), which also confirmed the strong binding with the pesticides, followed by their conversion into safer and smaller metabolites. The charge separation mechanism was elucidated by UV reflectance and photoluminescence data. Hydroxyl radicals were most frequently responsible for the degradation of pesticides as confirmed by scavenger analysis. The synthesized green-nano photocatalyst showed high reusability (up to 10th cycles), sensitivity and stability within the degradation process, presumably making it suitable for industrial applications.

A biomimetic beetle-like membrane with superoleophilic SiO2-induced oil coalescence on superhydrophilic CuC2O4 nanosheet arrays for effective O/W emulsion separation.

It is highly attractive to develop highly efficient oil-in-water (O/W) emulsion separation technologies for promoting the oily wastewater treatment. Herein, a novel inversely Stenocara beetle-like hierarchical structure of superhydrophobic SiO2 nanoparticle-decorated CuC2O4 nanosheet arrays were prepared on copper mesh membrane by bridging polydopamine (PDA) to make a SiO2/PDA@CuC2O4 membrane for substantially enhanced separation of O/W emulsions. The superhydrophobic SiO2 particles on the as-prepared SiO2/PDA@CuC2O4 membranes were served as localized active sites to induce coalescence of small-size oil droplets in oil-in-water (O/W) emulsions. Such innovated membrane delivered outstanding demulsification ability of O/W emulsion with a high separation flux of 2.5 kL⋅m-2⋅h-1 and its filtrate's chemical oxygen demand (COD) being 30 and 100 mg⋅L-1 for surfactant-free emulsion (SFE) and surfactant-stabilized emulsion (SSE), respectively, and also exhibited a good anti-fouling performance in cycling tests. The innovative design strategy developed in this work broadens the application of superwetting materials for oil-water separation and presents a promising prospect in practical oily wastewater treatment applications.

The microbial synergy and response mechanisms of hydrolysis-acidification combined microbial electrolysis cell system with stainless-steel cathode for textile-dyeing wastewater treatment.

Microbial electrolysis cell (MEC) has been existing problems such as poor applicability to real wastewater and lack of cost-effective electrode materials in the practical application of refractory wastewater. A hydrolysis-acidification combined MEC system (HAR-MECs) with four inexpensive stainless-steel and conventional carbon cloth cathodes for the treatment of real textile-dyeing wastewater, which was fully evaluated the technical feasibility in terms of parameter optimization, spectral analysis, succession and cooperative/competition effect of microbial. Results showed that the optimum performance was achieved with a 12 h hydraulic retention time (HRT) and an applied voltage of 0.7 V in the HAR-MEC system with a 100 µm aperture stainless-steel mesh cathode (SSM-100 µm), and the associated optimum BOD5/COD improvement efficiency (74.75 ± 4.32 %) and current density (5.94 ± 0.03 A·m-2) were increased by 30.36 % and 22.36 % compared to a conventional carbon cloth cathode. The optimal system had effective removal of refractory organics and produced small molecules by electrical stimulation. The HAR segment could greatly alleviate the imbalance between electron donors and electron acceptors in the real refractory wastewater and reduce the treatment difficulty of the MEC segment, while the MEC system improved wastewater biodegradability, amplified the positive and specific interactions between degraders, fermenters and electroactive bacteria due to the substrate complexity. The SSM-100 µm-based system constructed by phylogenetic molecular ecological network (pMEN) exhibited moderate complexity and significantly strong positive correlation between electroactive bacteria and fermenters. It is highly feasible to use HAR-MEC with inexpensive stainless-steel cathode for textile-dyeing wastewater treatment.

Toxicity determination, pollution source delineation, and microbial diversity evaluation of PAHs-contaminated sediments for an urban river.

The Feng-Sang River is a metropolitan river in Kaohsiung City, Taiwan. In this study, Feng-Sang River sediments were analyzed to investigate the distributions and sources of polycyclic aromatic hydrocarbons (PAHs). The Sediment Quality Guidelines (SQGs), potentially carcinogenic PAHs (TEQcarc ), and toxic equivalence quotient (TEQ) were applied to evaluate influences of PAHs on ecosystems and microbial diversities. Results indicate that PAHs concentrations varied between seasons and locations. The concentrations of ∑16 PAHs ranged from 73.6 to 603.8 ng/kg in dry seasons and from 2.3 to 199.3 ng/kg in wet seasons. This could be because of the flushing effect during wet seasons, which caused the movement and dilution of the PAH-contaminated sediments. Diagnostic ratio analysis infers that high PAHs levels were generated by combustion processes and vehicle traffic, and results from multivariate descriptive statistical analysis also demonstrate that the vehicular traffic pollution could be the major emission source of PAHs contamination. Comparisons of PAHs with SQGs indicate that PAHs concentrations in sediment were below the effects range low (ERL) values, and thus, the immediate threat to organisms might not be significant. The diagnostic ratio analyses are effective methods for PAH source appointment. The metagenomic assay results imply that sediments contained essential microbial species with eminent diversity. The detected PAH-degrading bacteria (Desulfatiglans, Dechloromonas, Sphingomonas, Methylobacterium, Rhodobacter, Clostridium, and Exiguobacterium) played a key role in PAHs biotransformation, and Dechloromonas and Rhodobacter had a higher relative abundance. Results of microbial diversity analyses indicate that the contaminated environment induced the changes of governing microbial groups in sediments. PRACTITIONER POINTS: Diagnostic ratio analyses are effective methods for PAHs source appointment. Microbial composition in sediments are highly affected by anthropogenic pollution. Combustion and vehicle traffic contribute to urban river sediments pollution by PAHs. Dechloromonas and Rhodobacter are dominant PAHs-degrading bacteria in sediments.

A phase II study of retifanlimab (INCMGA00012) in patients with squamous carcinoma of the anal canal who have progressed following platinum-based chemotherapy (POD1UM-202).

BACKGROUND: Locally advanced or metastatic squamous carcinoma of the anal canal (SCAC) has poor prognosis following platinum-based chemotherapy. Retifanlimab (INCMGA00012), a humanized monoclonal antibody targeting programmed death protein-1 (PD-1), demonstrated clinical activity across a range of solid tumors in clinical trials. We present results from POD1UM-202 (NCT03597295), an open-label, single-arm, multicenter, phase II study evaluating retifanlimab in patients with previously treated advanced or metastatic SCAC. PATIENTS AND METHODS: Patients ≥18 years of age had measurable disease and had progressed following, or were ineligible for, platinum-based therapy. Retifanlimab 500 mg was administered intravenously every 4 weeks. The primary endpoint was overall response rate (ORR) by independent central review. Secondary endpoints were duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Overall, 94 patients were enrolled. At a median follow-up of 7.1 months (range, 0.9-19.4 months), ORR was 13.8% [95% confidence interval (CI) 7.6% to 22.5%], with one complete response (1.1%) and 12 partial responses (12.8%). Responses were observed regardless of human immunodeficiency virus or human papillomavirus status, programmed death ligand 1 (PD-L1) expression, or liver metastases. Stable disease was observed in 33 patients (35.1%) for a DCR of 48.9% (95% CI 38.5% to 59.5%). Median DOR was 9.5 months (range, 5.6 months-not estimable). Median (95% CI) PFS and OS were 2.3 (1.9-3.6) and 10.1 (7.9-not estimable) months, respectively. Retifanlimab safety in this population was consistent with previous experience for the PD-(L)1 inhibitor class. CONCLUSIONS: Retifanlimab demonstrated clinically meaningful and durable antitumor activity, and an acceptable safety profile in patients with previously treated locally advanced or metastatic SCAC who have progressed on or are intolerant to platinum-based chemotherapy.

[Effects of sodium iodide symporter co-expression on proliferation and cytotoxic activity of chimeric antigen receptor T cells in vitro].

OBJECTIVE: To investigate the effects of co-expression of sodium iodide symporter (NIS) reporter gene on the proliferation and cytotoxic activity of chimeric antigen receptor (CAR)-T cells in vitro. METHODS: T cells expressing CD19 CAR (CAR-T cells), NIS reporter gene (NIS-T cells), and both (NIS-CAR-T cells) were prepared by lentiviral infection. The transfection rates of NIS and CAR were determined by flow cytometry, and the cell proliferation rate was assessed using CCK-8 assay at 24, 48 and 72 h of routine cell culture. The T cells were co-cultured with Nalm6 tumor cells at the effector-target ratios of 1∶2, 1∶1, 2∶1 and 4∶1 for 24, 48 and 72 h, and the cytotoxicity of CAR-T cells to the tumor cells was evaluated using lactate dehydrogenase (LDH) assay. ELISA was used to detect the release of IFN-γ and TNF-ß in the co-culture supernatant, and the function of NIS was detected with iodine uptake test. RESULTS: The CAR transfection rate was 91.91% in CAR-T cells and 99.41% in NIS-CAR-T cells; the NIS transfection rate was 47.83% in NIS-T cells and 50.24% in NIS- CAR-T cells. No significant difference in the proliferation rate was observed between CAR-T and NIS-CAR-T cells cultured for 24, 48 or 72 h (P> 0.05). In the co-cultures with different effector-target ratios, the tumor cell killing rate was significantly higher in CAR-T group than in NIS-CAR-T group at 24 h (P < 0.05), but no significant difference was observed between the two groups at 48 h or 72 h (P>0.05). Higher IFN-γ and TNF-ß release levels were detected in both CAR-T and NIS-CAR-T groups than in the control group (P < 0.05). NIS-T cells and NIS-CAR-T cells showed similar capacity of specific iodine uptake (P>0.05), which was significantly higher than that in the control T cells (P < 0.05). CONCLUSION: The co-expression of the NIS reporter gene does not affect CAR expression, proliferation or tumor cell-killing ability of CAR-T cells.

[Neuroendoscopy-assisted microneurosurgery for cerebellopontine angle cholesteatoma].

A total of 49 patients with cerebellopontine angle cholesteatoma from the Department of Neurosurgery, Affiliated Hospital of Xuzhou Medical University between January 2013 and January 2021 were recruited. All patients were evaluated by MRI scan before surgery and tumor resection was performed under microscope via retrosigmoid sinus approach. Then residual tumor was searched with 0°and 30°neuroendoscopy, and tumor resection was performed.Residual tumors were foundand resectedin 38 cases under theneuroendoscopy after routine microsurgery.Total and subtotalresections were performed in 44 cases and 5 cases, respectively. Complications included aseptic meningitis (n=8), cerebrospinal fluid leakage (n=1) and intracranial hematoma (n=2). Follow-up[42±3(6-72)months] was available in all patients. During follow-up, 45 cases (91.8%) had a Kar-nofsky Performance Status (KPS)score ≥80.Neuroendoscopy-assisted microsurgery for cerebellopontine angle cholesteatomas helps enhance the total resection rate and decrease the operative risk.