Efficacy of Acupuncture for Chronic Spontaneous Urticaria : A Randomized Controlled Trial.

BACKGROUND: The effectiveness of acupuncture for patients with chronic spontaneous urticaria (CSU), reported in a few small-scale studies, is not convincing. OBJECTIVE: To investigate whether acupuncture leads to better effects on CSU than sham acupuncture or waitlist control. DESIGN: A multicenter, randomized, sham-controlled trial. (Chinese Clinical Trial Registry: ChiCTR1900022994). SETTING: Three teaching hospitals in China from 27 May 2019 to 30 July 2022. PARTICIPANTS: 330 participants diagnosed with CSU. INTERVENTION: Participants were randomly assigned in a 1:1:1 ratio to receive acupuncture, sham acupuncture, or waitlist control over an 8-week study period (4 weeks for treatment and another 4 weeks for follow-up). MEASUREMENTS: The primary outcome was the mean change from baseline in the Weekly Urticaria Activity Score (UAS7) at week 4. Secondary outcomes included itch severity scores, self-rated improvement, and Dermatology Life Quality Index scores. RESULTS: The mean change in UAS7 (range, 0 to 42) for acupuncture from baseline (mean score, 23.5 [95% CI, 21.8 to 25.2]) to week 4 (mean score, 15.3 [CI, 13.6 to 16.9]) was -8.2 (CI, -9.9 to -6.6). The mean changes in UAS7 for sham acupuncture and waitlist control from baseline (mean scores, 21.9 [CI, 20.2 to 23.6] and 22.1 [CI, 20.4 to 23.8], respectively) to week 4 (mean scores, 17.8 [CI, 16.1 to 19.5] and 20.0 [CI, 18.3 to 21.6], respectively) were -4.1 (CI, -5.8 to -2.4) and -2.2 (CI, -3.8 to -0.5), respectively. The mean differences between acupuncture and sham acupuncture and waitlist control were -4.1 (CI, -6.5 to -1.8) and -6.1 (CI, -8.4 to -3.7), respectively, which did not meet the threshold for minimal clinically important difference. Fifteen participants (13.6%) in the acupuncture group and none in the other groups reported adverse events. Adverse events were mild or transient. LIMITATION: Lack of complete blinding, self-reported outcomes, limited generalizability because antihistamine use was disallowed, and short follow-up period. CONCLUSION: Compared with sham acupuncture and waitlist control, acupuncture produced a greater improvement in UAS7, although the difference from control was not clinically significant. Increased adverse events were mild or transient. PRIMARY FUNDING SOURCE: The National Key R&D Program of China and the Science and Technology Department of Sichuan Province.

Environmental Impact Assessment for the Use of an Orally Aerosolized Adenovirus Type-5 Vector-Based COVID-19 Vaccine in Randomized Clinical Trials.

BACKGROUND: An orally aerosolized adenovirus type-5 vector-based coronavirus disease 2019 (COVID-19) vaccine (Ad5-nCoV) has recently been authorized for boosting immunization in China. Our study aims to assess the environmental impact of the use of aerosolized Ad5-nCoV. METHODS: We collected air samples from rooms, swabs from the desks on which the vaccine nebulizer was set, mask samples from participants, and blood samples of nurses who administered the inoculation in the clinical trials. The viral load of adenovirus type-5 vector in the samples and the antibody levels against the wild-type severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain in serum were detected. RESULTS: Only one (4.00%) air sample collected before initiation of vaccination was positive and most air samples collected during and after vaccination were positive (97.96%, 100%, respectively). All nurses in trial A showed at least 4-fold increase of the neutralizing antibody against SARS-CoV-2 after initiation of the study. In trial B, the proportion of positive mask samples was 72.97% at 30 minutes after vaccination, 8.11% at day 1, and 0% at days 3, 5, and 7. CONCLUSIONS: Vaccination with the orally aerosolized Ad5-nCoV could result in some spillage of the vaccine vector viral particles in the environment and cause human exposure. Clinical Trials Registration. NCT04840992 and NCT05303584.

Clinical value of DPOC for detecting and removing residual common bile duct stones (video).

BACKGROUND: This study aims to evaluate the efficacy and safety of detecting and removing residual common bile duct stones (CBDS) using direct peroralcholangioscopy (DPOC) after performing endoscopic retrograde cholangiopancreatography (ERCP) for stone retrieval. METHODS: From January 5, 2017 to December 27, 2017, a total of 164 cases of choledocholithiasis were treated by ERCP for stone retrieval. According to the inclusion and exclusion criteria, the remaining 79 cases (39 males; mean age: 63.3 years old, range: 52-79 years old) were enrolled in the present study. The maximum transverse stone diameter was 6-15 mm (12.7 ± 4.2 mm), as determined by ERCP. Furthermore, there were 57 cases of multiple stones (number of stones: two in 41 cases, three in nine cases, and ≥ 4 in seven cases), 13 cases of post-mechanical lithotripsy, and nine cases of broken stones. RESULTS: The overall success rate of DPOC was 94.9% (75/79). Furthermore, 18.7%(14/75) of cases were directly inserted, 72%(54/75) of cases required guide wire assistance, and 9.3%(7/75) of cases were successfully inserted with overtube assistance. The average insertion time was 7-17 min (4.9 ± 2.9 min). Residual stones were detected in 19 cases (25.3%), and all of which were < 5 mm in diameter. Moreover, five cases of formed stones were removed by basket and balloon catheter, while the remaining cases were cleaned after irrigation and suction. There were no serious complications. CONCLUSION: DPOC is safe and effective for both the detection and removal of residual CBDS after conventional ERCP.

High level of soluble interleukin-2 receptor in serum predicts treatment resistance and poor progression-free survival in multiple myeloma.

The IL-2/IL-2 receptor (IL-2R) system plays a central role in maintaining normal T cell immunity, and its disturbance is associated with several hematologic disorders. Studies have found in several types of lymphoma that abnormal amounts of soluble IL-2R (sIL-2R) may result in imbalance of the IL-2/IL-2R system and hence of the T cell immunoregulation. Whether the level of sIL-2R in blood could predict treatment outcomes or not needs to be investigated in multiple myeloma (MM) patients. The level of sIL-2R in serum was measured using enzyme-linked immunosorbent assay (ELISA) in 81 patients with newly diagnosed MM. Twenty-six patients (32.1%) were treated with bortezomib-based regimens and 55patients (67.9%) received old drugs-based regimens. The mean concentration of sIL-2R for myeloma patients was 8.51 ng/ml, significantly higher than that of healthy controls (0.56 ng/ml, p < 0.0001). The best cutoff value for sIL-2R in predicting high risk for disease progression is 6.049 ng/ml with an area under curve (AUC) of 0.665 (p = 0.013). Thirty-six patients (44.4%) were classified as higher sIL-2R level group (> 6.049 ng/ml), and 45 patients (55.6%) as lower group (≤ 6.049 ng/ml). The overall response rate (ORR) was 60.0% in lower sIL-2R level group, and 41.7% in higher level group (p = 0.156). The median progression-free survival (PFS) and overall survival (OS) was 12 months (range, 2.0-65 months) and 20 months (range, 2.0-118 months), respectively. In a multivariate survival analysis, including Eastern Cooperative Oncology Group performance status score, treatment response, and sIL-2R level, it was found that all these three parameters were significantly independent prognostic factors for PFS (p = 0.032, 0.016, and 0.043, respectively), but none factors maintained their value in predicting OS. Subgroup analysis revealed that high level of sIL-2R is correlated with significantly inferior PFS in patients treated with bortezomib-based regimens (p = 0.004). Serum sIL-2R level is an independent prognostic factor for PFS, indicating novel drugs targeting the imbalance of IL-2/IL-2R system may be a promising strategy in MM.

High level of interleukin-10 in serum predicts poor prognosis in multiple myeloma.

BACKGROUND: Interleukin-10 (IL-10) is a inhibiting inflammatory cytokine that plays an important role in immune suppressive microenvironment in multiple myeloma (MM). Whether the level of serum IL-10 could predict treatment response and survival outcomes or not needs to be investigated in MM patients. METHODS: The level of IL-10 in serum was measured using enzyme-linked immunosorbent assay in 188 patients with newly diagnosed MM. RESULTS: The best cutoff value for IL-10 in predicting survival is 169.69 pg ml(-1) with an area under the curve (AUC) value of 0.747 (P<0.001). In all, 92 patients (48.9%) were classified as high-IL-10 group (>169.96 pg ml(-1)) and 96 patients (51.1%) as low-IL-10 group (⩽169.96 pg ml(-1)). The overall response rate (ORR) was 79.2% in low-IL-10 group, significantly higher than that in high-IL-10 group (53.3%, P<0.001). Patients in low-IL-10 group had significantly better survival compared with those in high-IL-10 group (3-year PFS rate: 69.3% vs 13.3%, P<0.001; 3-year OS rate: 93.6% vs 51.9%, P<0.001). Multivariate analysis revealed that serum IL-10 level >169.96 pg ml(-1) at diagnosis and certain cytogenetic abnormalities were two adverse factors for PFS and OS. CONCLUSIONS: Our data suggest that serum IL-10 at diagnosis is a novel, powerful predictor of prognosis for MM.

Diastereoselective Synthesis of Dispirobarbiturates through Et3N-Catalyzed [3 + 2] Cycloaddition of Barbiturate-Based Olefins with 3-Isothiocyanato Oxindoles.

Under catalysis of 10 mol % of Et3N, the [3 + 2] cycloaddition of barbiturate-based olefins with 3-isothiocyanato oxindoles underwent smoothly and afforded the desired dispirobarbiturates in up to 99% yield with up to 99:1 dr. The relative configuration of the dispirobarbiturates was unambiguously determined by X-ray single-crystal structure analysis. The reaction mechanism was proposed to shed light on the diastereoselective formation of the dispirobarbiturates.

Immunogenicity and safety of an enterovirus 71 vaccine in healthy Chinese children and infants: a randomised, double-blind, placebo-controlled phase 2 clinical trial.

BACKGROUND: Enterovirus 71 (EV71) outbreaks are a socioeconomic burden, especially in the western Pacific region. Results of phase 1 clinical trials suggest an EV71 vaccine has a clinically acceptable safety profile and immunogenicity. We aimed to assess the best possible dose and formulation, immunogenicity, and safety profile of this EV71 vaccine in healthy Chinese children. METHODS: This randomised, double-blind, placebo-controlled, phase 2 trial was undertaken at one site in Donghai County, Jiangsu Province, China. Eligible participants were healthy boys or girls aged 6­36 months. Participants were randomly assigned (1:1:1:1:1) to receive either 160 U, 320 U, or 640 U alum-adjuvant EV71 vaccine, 640 U adjuvant-free EV71 vaccine, or a placebo (containing alum adjuvant only), according to a blocked randomisation list generated by SAS 9.1. Participants and investigators were masked to the assignment. The primary endpoint was anti-EV71 neutralising antibody geometric mean titres (GMTs) at day 56, analysed according to protocol. The study is registered with ClinicalTrials.gov, number NCT01399853. FINDINGS: We randomly assigned 1200 participants, 240 (120 aged 6­11 months [infants] and 120 aged 12­36 months [children]) of whom were assigned to each dose. 1106 participants completed the study and were included in the according-to-protocol analysis. The main reasons for dropout were withdrawal of consent and refusal to donate a blood sample. Infants who received the 640 U adjuvant vaccine had the highest GMTs on day 56 (742·2 [95% CI 577·3­954·3]), followed by those who received the 320 U formulation (497·9 [383·1­647·0]). For children, those who received the 320 U formulation had the highest GMTs on day 56 (1383·2 [1037·3­1844·5]). Participants who received the vaccine had significantly higher GMTs than did who received placebo (p<0·0001). For the subgroup of participants who were seronegative at baseline, both infants and children who received the 640 U adjuvant vaccine had the highest GMTs on day 56 (522·8 [403·9­676·6] in infants and 708·4 [524·1­957·6] in children), followed by those who received the 320 U adjuvant vaccine (358·2 [280·5­457·5] in infants and 498·0 [383·4­646·9] in children). 549 (45·8%) of 1200 participants (95 CI 42·9­48·6%) reported at least one injection-site or systemic adverse reaction, but the incidence of adverse reactions did not differ significantly between groups (p=0·36). The 640 U alum-adjuvant vaccine group had a significantly higher incidence of induration than did the 640 U adjuvant-free group (p=0·001). INTERPRETATION: Taking immunogenicity, safety, and production capacity into account, the 320 U alum-adjuvant formulation of the EV71 vaccine is probably the best possible formulation for phase 3 trials. FUNDING: The National Science and Technology Major Project (2011ZX10004-902) of the Chinese Ministry of Science and Technology, China's 12­5 National Major Infectious Disease Program (2012ZX10002-001), and Beijing Vigoo Biological.

Efficacy, safety, and immunology of an inactivated alum-adjuvant enterovirus 71 vaccine in children in China: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: A vaccine for enterovirus 71 (EV71) is needed to address the high burden of disease associated with infection. We assessed the efficacy, safety, immunogenicity, antibody persistence, and immunological correlates of an inactivated alum-adjuvant EV71 vaccine. METHODS: We did a randomised, double-blind, placebo-controlled, phase 3 trial. Healthy children aged 6-35 months from four centres in China were randomly assigned (1:1) to receive vaccine or alum-adjuvant placebo at day 0 and 28, according to a randomisation list (block size 30) generated by an independent statistician. Investigators and participants and their guardians were masked to the assignment. Primary endpoints were EV71-associated hand, foot, and mouth disease (HFMD) and EV71-associated disease during the surveillance period from day 56 to month 14, analysed in the per-protocol population. This study is registered with ClinicalTrials.gov, number NCT01508247. FINDINGS: 10,245 participants were enrolled and assigned: 5120 to vaccine versus 5125 to placebo. 4907 (with three cases of EV71-associated HFMD and eight cases of EV71-associated disease) versus 4939 (with 30 cases of EV71-associated HFMD and 41 cases of EV71-associated disease) were included in the primary efficacy analysis. Vaccine efficacy was 90·0% (95% CI 67·1-96·9) against EV71-associated HFMD (p=0·0001) and 80·4% (95% CI 58·2-90·8) against EV71-associated disease (p<0·0001). Serious adverse events were reported by 62 of 5117 (1·2%) participants in the vaccine group versus 75 of 5123 (1·5%) in the placebo group (p=0·27). Adverse events occurred in 3644 (71·2%) versus 3603 (70·3%; p=0·33). INTERPRETATION: EV71 vaccine provides high efficacy, satisfactory safety, and sustained immunogenicity. FUNDING: China's 12-5 National Major Infectious Disease Program, Beijing Vigoo Biological.

Increased lymphocyte to monocyte ratio is associated with better prognosis in patients with newly diagnosed metastatic nasopharyngeal carcinoma receiving chemotherapy.

Inflammation has been demonstrated to be widely involved in the carcinogenesis of nasopharyngeal carcinoma (NPC). However, the prognostic significance of lymphocyte to monocyte ratio (LMR) in metastatic NPC is not fully addressed. The purpose of the study is to investigate the prognostic impact of pre-treatment absolute lymphocyte count (ALC), absolute monocyte count (AMC), and LMR on patients with newly diagnosed metastatic NPC undergoing chemotherapy. Between January 2006 and December 2010, patients with newly diagnosed metastatic NPC undergoing chemotherapy were retrospectively collected. The prognostic significance of baseline clinical features and inflammatory markers was investigated. A total of 256 patients were eligible for the study. The best cut-off value of ALC, AMC, and LMR was 2.25 × 10(9)/L, 0.35 × 10(9)/L, and 5.07, respectively. Patients in the high LMR group had a significantly longer overall survival (OS) (25.0 months [24.50-25.49]) than patients in the low LMR group (16.0 months [15.51-16.49]; p < 0.001). In addition, ALC ≥ 2.25 × 10(9)/L (HR, 0.59; 95% CI, 0.43-0.81; p = 0.001) and LMR ≥ 5.07 (HR, 0.42; 95% CI, 0.30-0.59; p < .001) remained as independent prognostic factors for superior OS, while AMC did not retained its prognostic significance in COX multivariate analysis. Pre-treatment ALC and LMR were demonstrated to be independent prognostic factors in patient with newly diagnosed metastatic NPC receiving chemotherapy. Future prospective studies are needed to validate the findings.

Enhancing tunnel crack detection with linear seam using mixed stride convolution and attention mechanism.

Cracks in tunnel lining structures constitute a common and serious problem that jeopardizes the safety of traffic and the durability of the tunnel. The similarity between lining seams and cracks in terms of strength and morphological characteristics renders the detection of cracks in tunnel lining structures challenging. To address this issue, a new deep learning-based method for crack detection in tunnel lining structures is proposed. First, an improved attention mechanism is introduced for the morphological features of lining seams, which not only aggregates global spatial information but also features along two dimensions, height and width, to mine more long-distance feature information. Furthermore, a mixed strip convolution module leveraging four different directions of strip convolution is proposed. This module captures remote contextual information from various angles to avoid interference from background pixels. To evaluate the proposed approach, the two modules are integrated into a U-shaped network, and experiments are conducted on Tunnel200, a tunnel lining crack dataset, as well as the publicly available crack datasets Crack500 and DeepCrack. The results show that the approach outperforms existing methods and achieves superior performance on these datasets.

First-line combination of gemcitabine, oxaliplatin, and L-asparaginase (GELOX) followed by involved-field radiation therapy for patients with stage IE/IIE extranodal natural killer/T-cell lymphoma.

BACKGROUND: Extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) is a distinct subtype of non-Hodgkin lymphoma in which the upper aerodigestive tract is the most commonly involved site. To date, optimal treatment strategies and prognosis for patients with ENKTL have not been fully defined. METHODS: This prospective study was conducted to evaluate the efficacy and safety profiles of first-line combined gemcitabine, oxaliplatin, and L-asparaginase (GELOX) followed by involved-field radiation therapy for patients with stage IE/IIE ENKTL. The primary endpoints were the complete response rate, the objective response rate, and toxicities. Secondary endpoints were overall survival and progression-free survival. RESULTS: Twenty-seven patients with newly diagnosed ENKTL were enrolled and completed the entire course of treatment. At the end of treatment, the overall response rate was 96.3%, including 20 patients (74.1%) who attained a complete response and 6 patients (22.2%) who attained a partial response. No patients developed disease progression during therapy. Grade 1 and 2 toxicities were frequent during GELOX, but grade 3 and 4 toxicities were few, and no treatment-related deaths occurred. At a median follow-up of 27.37 months, 7 patients (25.9%) experienced disease progression, and 4 of those patients died of disease. The rates of 2-year overall and progression-free survival were both 86%, and patients who attained a complete response at the end of treatment had significantly longer progression-free survival (P = .012) and overall survival (P = .021) than patients who did not attain a complete response. CONCLUSIONS: The current results indicated that GELOX followed by involved-field radiation therapy can be an effective and feasible treatment strategy for patients with stage IE/IIE ENKTL of the upper aerodigestive tract. These results will require further investigation in larger prospective trials.

MK8617 inhibits M1 macrophage polarization and inflammation via the HIF-1α/GYS1/UDPG/P2Y14 pathway.

Background: Nonresolving inflammation is a major driver of disease and needs to be taken seriously. Hypoxia-inducible factor (HIF) is closely associated with inflammation. Hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs), as stabilizers of HIF, have recently been reported to have the ability to block inflammation. We used MK8617, a novel HIF-PHI, to study its effect on macrophage inflammation and to explore its possible mechanisms. Methods: Cell viability after MK8617 and lipopolysaccharide (LPS) addition was assessed by Cell Counting Kit-8 (CCK8) to find the appropriate drug concentration. MK8617 pretreated or unpretreated cells were then stimulated with LPS to induce macrophage polarization and inflammation. Inflammatory indicators in cells were assessed by real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR), western blot (WB) and immunofluorescence (IF). The level of uridine diphosphate glucose (UDPG) in the cell supernatant was measured by ELISA. Purinergic G protein-coupled receptor P2Y14, as well as hypoxia-inducible factor-1α (HIF-1α) and glycogen synthase 1 (GYS1) were detected by qRT-PCR and WB. After UDPG inhibition with glycogen phosphorylase inhibitor (GPI) or knockdown of HIF-1α and GYS1 with lentivirus, P2Y14 and inflammatory indexes of macrophages were detected by qRT-PCR and WB. Results: MK8617 reduced LPS-induced release of pro-inflammatory factors as well as UDPG secretion and P2Y14 expression. UDPG upregulated P2Y14 and inflammatory indicators, while inhibition of UDPG suppressed LPS-induced inflammation. In addition, HIF-1α directly regulated GYS1, which encoded glycogen synthase, an enzyme that mediated the synthesis of glycogen by UDPG, thereby affecting UDPG secretion. Knockdown of HIF-1α and GYS1 disrupted the anti-inflammatory effect of MK8617. Conclusions: Our study demonstrated the role of MK8617 in macrophage inflammation and revealed that its mechanism of action may be related to the HIF-1α/GYS1/UDPG/P2Y14 pathway, providing new therapeutic ideas for the study of inflammation.

Safety and immunogenicity of aerosolised Ad5-nCoV, intramuscular Ad5-nCoV, or inactivated COVID-19 vaccine CoronaVac given as the second booster following three doses of CoronaVac: a multicentre, open-label, phase 4, randomised trial.

BACKGROUND: Aerosolised Ad5-nCoV is the first approved mucosal respiratory COVID-19 vaccine to be used as a booster after the primary immunisation with COVID-19 vaccines. This study aimed to evaluate the safety and immunogenicity of aerosolised Ad5-nCoV, intramuscular Ad5-nCoV, or inactivated COVID-19 vaccine CoronaVac given as the second booster. METHODS: This is an open-label, parallel-controlled, phase 4 randomised trial enrolling healthy adult participants (≥18 years) who had completed a two-dose primary immunisation and a booster immunisation with inactivated COVID-19 vaccines (CoronaVac only) at least 6 months before, in Lianshui and Donghai counties, Jiangsu Province, China. We recruited eligible participants from previous trials in China (NCT04892459, NCT04952727, and NCT05043259) as cohort 1 (with the serum before and after the first booster dose available), and from eligible volunteers in Lianshui and Donghai counties, Jiangsu Province, as cohort 2. Participants were randomly assigned at a ratio of 1:1:1, using a web-based interactive response randomisation system, to receive the fourth dose (second booster) of aerosolised Ad5-nCoV (0·1 mL of 1·0 × 1011 viral particles per mL), intramuscular Ad5-nCoV (0·5 mL of 1·0 × 1011 viral particles per mL), or inactivated COVID-19 vaccine CoronaVac (0·5 mL), respectively. The co-primary outcomes were safety and immunogenicity of geometric mean titres (GMTs) of serum neutralising antibodies against prototype live SARS-CoV-2 virus 28 days after the vaccination, assessed on a per-protocol basis. Non-inferiority or superiority was achieved when the lower limit of the 95% CI of the GMT ratio (heterologous group vs homologous group) exceeded 0·67 or 1·0, respectively. This study was registered with ClinicalTrials.gov, NCT05303584 and is ongoing. FINDINGS: Between April 23 and May 23, 2022, from 367 volunteers screened for eligibility, 356 participants met eligibility criteria and received a dose of aerosolised Ad5-nCoV (n=117), intramuscular Ad5-nCoV (n=120), or CoronaVac (n=119). Within 28 days of booster vaccination, participants in the intramuscular Ad5-nCoV group reported a significantly higher frequency of adverse reactions than those in the aerosolised Ad5-nCoV and intramuscular CoronaVac groups (30% vs 9% and 14%, respectively; p<0·0001). No serious adverse events related to the vaccination were reported. The heterologous boosting with aerosolised Ad5-nCoV triggered a GMT of 672·4 (95% CI 539·7-837·7) and intramuscular Ad5-nCoV triggered a serum neutralising antibody GMT of 582·6 (505·0-672·2) 28 days after the booster dose, both of which were significantly higher than the GMT in the CoronaVac group (58·5 [48·0-71·4]; p<0·0001). INTERPRETATION: A heterologous fourth dose (second booster) with either aerosolised Ad5-nCoV or intramuscular Ad5-nCoV was safe and highly immunogenic in healthy adults who had been immunised with three doses of CoronaVac. FUNDING: National Natural Science Foundation of China, Jiangsu Provincial Science Fund for Distinguished Young Scholars, and Jiangsu Provincial Key Project of Science and Technology Plan.

[Evaluation of nutrient release profiles from polymer coated fertilizers using Fourier transform mid-infrared photoacoustic spectroscopy].

The acrylate-like materials were used to develop the polymer coated controlled release fertilizer, the nutrients release profiles were determined, meanwhile the Fourier transform mid-infrared photoacoustic spectra of the coatings were recorded and characterized; GRNN model was used to predict the nutrients release profiles using the principal components of the mid-infrared photoacoustic spectra as input. Results showed that the GRNN model could fast and effectively predict the nutrient release profiles, and the predicted calibration coefficients were more than 0.93; on the whole, the prediction errors (RMSE) were influenced by the profiling depth of the spectra, the average prediction error was 10.28%, and the spectra from the surface depth resulted in a lowest prediction error with 7.14%. Therefore, coupled with GRNN modeling, Fourier transform mid-infrared photoacoustic spectroscopy can be used as an alternative new technique in the fast and accurate prediction of nutrient release from polymer coated fertilizer.

Drug resistance biomarker ABCC4 of selinexor and immune feature in multiple myeloma.

The treatment of relapse or refractory multiple myeloma (RRMM) is still a big challenge in clinic. Recently, several clinical trials indicated that the XPO1 inhibitor, selinexor could significantly improve the remission rate in MM patients. However, the heterogeneous genetic background greatly influenced the efficiency of selinexor among MM. Here, we tried to characterized the biomarkers associated with selinexor sensitivity by analyzing gene expression data in MM patients. We found the cytogenetic background of selinexor sensitive MM patients was not limited to specific cytogenetic subtypes. In addition, by weighted gene co-expression network analysis (WGCNA), we obtained 10 key genes which showed a strong correlation with the selinexor sensitivity in MM patients. Notably, ABCC4 (MRP4) was the only gene which was both differentially expressed and proved to be clinical prognostic valuable (both for event-free survival and overall survival) in MM patients. We further validated the heterogenous expression of ABCC4 in MM cell lines and its value as a novel indicator for selinexor sensitivity. Moreover, immune infiltration analysis showed that ABCC4 expression had a significantly positive correlation with NK infiltration as well as immunotherapy target TIM-3 (HAVCR2) expression. Collectively, our findings indicated that ABCC4 might be a predictive biomarker of selinexor sensitivity in MM patients, which could be enhanced if combined with immunotherapy drugs such as TIM-3 inhibitor.

Safety and immunogenicity of heterologous boost immunisation with an orally administered aerosolised Ad5-nCoV after two-dose priming with an inactivated SARS-CoV-2 vaccine in Chinese adults: a randomised, open-label, single-centre trial.

BACKGROUND: Due to waning immunity and protection against infection with SARS-CoV-2, a third dose of a homologous or heterologous COVID-19 vaccine has been proposed by health agencies for individuals who were previously primed with two doses of an inactivated COVID-19 vaccine. METHODS: We did a randomised, open-label, controlled trial to evaluate the safety and immunogenicity of heterologous boost immunisation with an orally administered aerosolised adenovirus type-5 vector-based COVID-19 vaccine (Ad5-nCoV) in Chinese adults (≥18 years old) who had previously received two doses of an inactivated SARS-CoV-2 vaccine-Sinovac CoronaVac. Eligible participants were randomly assigned (1:1:1) to receive a heterologous booster vaccination with a low dose (1·0 × 1011 viral particles per mL; 0·1 mL; low dose group), or a high dose (1·0 × 1011 viral particles per mL; 0·2 mL; high dose group) aerosolised Ad5-nCoV, or a homologous intramuscular vaccination with CoronaVac (0·5 mL). Only laboratory staff were masked to group assignment. The primary endpoint for safety was the incidence of adverse reactions within 14 days after the booster dose. The primary endpoint for immunogenicity was the geometric mean titres (GMTs) of serum neutralising antibodies (NAbs) against live SARS-CoV-2 virus 14 days after the booster dose. This study was registered with ClinicalTrials.gov, NCT05043259. FINDINGS: Between Sept 14 and 16, 2021, 420 participants were enrolled: 140 (33%) participants per group. Adverse reactions were reported by 26 (19%) participants in the low dose group and 33 (24%) in the high dose group within 14 days after the booster vaccination, significantly less than the 54 (39%) participants in the CoronaVac group (p<0·0001). The low dose group had a serum NAb GMT of 744·4 (95% CI 520·1-1065·6) and the high dose group had a GMT of 714·1 (479·4-1063·7) 14 days after booster dose, significantly higher than the GMT in the CoronaVac group (78·5 [60·5-101·7]; p<0·0001). INTERPRETATION: We found that a heterologous booster vaccine with an orally administered aerosolised Ad5-nCoV is safe and highly immunogenic in adults who have previously received two doses of CoronaVac as the primary series vaccination. FUNDING: National Natural Science Foundation of China and Jiangsu Provincial Key Research and Development Program.

Efficacy of combined angiotensin II receptor blocker with tripterygium glycosides on diabetic nephropathy: A protocol for meta-analysis.

BACKGROUND: Several studies have reported good results for angiotensin II receptor blockers (ARB) combined with tripterygium glycosides (TGs) in the treatment of diabetic nephropathy (DN). However, because a small number of cases were included in each study, the statistical power was limited. Therefore, we performed a protocol for meta-analysis to further evaluate the clinical efficacy and safety of combined ARB and TGs in treatment of DN. METHODS: The protocol was written following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement guidelines. We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data, Science Direct up to April 2021. Outcome measures were 24-h urinary total protein, urinary albumin excretion rate, serum creatinine, blood urea nitrogen, albumin, hemoglobin A1c, ß2-microglobulin and serum glutamic pyruvic transaminase. The risk of bias assessment of the included studies was performed by two authors independently using the tool recommended in the Cochrane Handbook for Systematic Reviews of Interventions (version 5.1.0). We performed meta-analysis using STATA 11.0. RESULTS: The review will add to the existing literature by showing compelling evidence and improved guidance in clinic settings. CONCLUSION: The findings will provide helpful evidence for the application of combined ARB and TGs in the treatment of DN. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/ARGE3.

High effective adsorption of Pb(II) from solution by biochar derived from torrefaction of ammonium persulphate pretreated bamboo.

Biochar was prepared by torrefaction of ammonium persulphate pretreated bamboo (labeled as APBC) and applied into elimination of Pb(II) from water solutions. APBC was characterized by N2 adsorption-desorption isotherms, elemental and Zeta potential analyses, SEM-EDS, XPS, and FTIR. Abundant N- and O-containing groups appeared atop APBC. Batch sorption assays revealed that APBC had high affinity and strong sorption ability towards Pb(II). The high Pb(II) adsorbing ability was attributed to the high contents of N- and O-containing functional groups of APBC. The adsorption mechanism mainly occurred by inner-sphere surface complexation. Hence, torrefaction of ammonium persulphate pretreated bamboo is a promising strategy for producing efficient biochar that is applicable for industrial wastewater treatment.

Safety and efficacy of thalidomide in patients with transfusion-dependent ß-thalassemia: a randomized clinical trial.

Thalidomide induces γ-globin expression in erythroid progenitor cells, but its efficacy on patients with transfusion-dependent ß-thalassemia (TDT) remains unclear. In this phase 2, multi-center, randomized, double-blind clinical trial, we aimed to determine the safety and efficacy of thalidomide in TDT patients. A hundred patients of 14 years or older were randomly assigned to receive placebo or thalidomide for 12 weeks, followed by an extension phase of at least 36 weeks. The primary endpoint was the change of hemoglobin (Hb) level in the patients. The secondary endpoints included the red blood cell (RBC) units transfused and adverse effects. In the placebo-controlled period, Hb concentrations in patients treated with thalidomide achieved a median elevation of 14.0 (range, 2.5 to 37.5) g/L, whereas Hb in patients treated with placebo did not significantly change. Within the 12 weeks, the mean RBC transfusion volume for patients treated with thalidomide and placebo was 5.4 ± 5.0 U and 10.3 ± 6.4 U, respectively (P < 0.001). Adverse events of drowsiness, dizziness, fatigue, pyrexia, sore throat, and rash were more common with thalidomide than placebo. In the extension phase, treatment with thalidomide for 24 weeks resulted in a sustainable increase in Hb concentrations which reached 104.9 ± 19.0 g/L, without blood transfusion. Significant increase in Hb concentration and reduction in RBC transfusions were associated with non ß0/ß0 and HBS1L-MYB (rs9399137 C/T, C/C; rs4895441 A/G, G/G) genotypes. These results demonstrated that thalidomide is effective in patients with TDT.

Phase II trial of XELOX as first-line treatment for patients with advanced gastric cancer.

BACKGROUND: The prognosis of patients with advanced gastric cancer (AGC) remains poor, and no single chemotherapy regimen is recognized as a global standard. A phase II trial was conducted to determine the efficacy and tolerability of capecitabine and oxaliplatin (XELOX) given every 3 weeks in combination in patients with AGC. METHODS: Patients with previously untreated AGC received intravenous oxaliplatin 130 mg/m(2) over 2 h on day 1 plus oral capecitabine 1,000 mg/m(2) twice daily on days 1-14, every 3 weeks. Treatment was continued for 8 cycles or until disease progression or intolerable toxicity. RESULTS: Fifty patients were enrolled. In total, 210 cycles of XELOX were delivered. The OVERALL response rate was 42% (95% CI 28.6-56.7), with 2 complete and 19 partial responses. At 15.2 months of median follow-up, median time to progression and overall survival were 5.8 (95% CI 3.4-8.2) and 11.1 (95% CI 5.6-16.5) months, respectively. The most common hematological adverse event was neutropenia (56% of patients); grade 3-4 neutropenia was observed in 6 patients, with neutropenic fever in only 2 patients. The most common non-hematological toxicities were vomiting (34%), hand-foot syndrome (26%), diarrhea (24%) and neurosensory toxicity (22%). There were no treatment-related deaths. CONCLUSIONS: XELOX is active for the first-line treatment of AGC with a manageable tolerability profile.