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Figure 1. Anti-tumor response.

Figure 5. PD-1 level in tumor-infiltrated T-cells.

Figure 2. Progression-free survival.

Figure 3. Ratio of peripheral memory T-cells during camrelizumab monotherapy and decitabine-plus-camrelizumab therapy.

Purpose:Programmed death-1 (PD-1) blockade monotherapy is effective in relapsed/refractory classical Hodgkin lymphoma (cHL), but a subset of patients is recalcitrant to PD-1 inhibitors and only a minority of patients achieves durable remission. Effective treatment regimens for those with relapsed/progressive cHL after single-agent anti-PD-1 are urgently needed. Anti-PD-1 combination with the DNA-demethylating agent decitabine showed positive preliminary results in our test cohort patients who were resistant to anti-PD-1. Here, we assess the efficacy of decitabine plus anti-PD-1 therapy in an expansion cohort and after longer follow-up.Patients and Methods:We present the response and progression-free survival rates from patients with relapsed/refractory cHL who relapsed/progressed after prior anti-PD-1 monotherapy, and who received decitabine (10 mg/day, days 1–5) plus the anti-PD-1 camrelizumab (200 mg, day 8), every 3 weeks in a phase II trial (ClinicalTrials.gov: NCT02961101 and NCT03250962).Results:Overall, 51 patients (test cohort: 25, expansion cohort: 26) were treated and 50 evaluated for efficacy. The objective response rate was 52% [nine complete responses (CR); 36%] in the test cohort, and 68% (six CRs; 24%) in the expansion cohort. Median progression-free survival with decitabine plus camrelizumab was 20.0 and 21.6 months, respectively, which was significantly longer than that achieved with prior anti-PD-1 monotherapy. Durable response was observed in an estimated 78% of patients who achieved CR at 24 months. After decitabine plus camrelizumab, the ratio increase of circulating peripheral central memory T cells directly correlated with both clinical response and progression-free survival.Conclusions:Decitabine plus camrelizumab is associated with high response rates and long-term benefits in patients with relapsed/refractory cHL who failed PD-1 inhibitors.

Supplementary Data

Figure 4. Ratio of peripheral central memory T-cells and association with progression-free survival.

Purpose: Programmed death-1 (PD-1) blockade monotherapy is effective in relapsed/refractory classical Hodgkin lymphoma (cHL), but a subset of patients is recalcitrant to PD-1 inhibitors and only a minority of patients achieves durable remission. Effective treatment regimens for those with relapsed/progressive cHL after single-agent anti-PD-1 are urgently needed. Anti-PD-1 combination with the DNA-demethylating agent decitabine showed positive preliminary results in our test cohort patients who were resistant to anti-PD-1. Here, we assess the efficacy of decitabine plus anti-PD-1 therapy in an expansion cohort and after longer follow-up. Patients and Methods: We present the response and progression-free survival rates from patients with relapsed/refractory cHL who relapsed/progressed after prior anti-PD-1 monotherapy, and who received decitabine (10 mg/day, days 1–5) plus the anti-PD-1 camrelizumab (200 mg, day 8), every 3 weeks in a phase II trial (ClinicalTrials.gov: NCT02961101 and NCT03250962). Results: Overall, 51 patients (test cohort: 25, expansion cohort: 26) were treated and 50 evaluated for efficacy. The objective response rate was 52% [nine complete responses (CR); 36%] in the test cohort, and 68% (six CRs; 24%) in the expansion cohort. Median progression-free survival with decitabine plus camrelizumab was 20.0 and 21.6 months, respectively, which was significantly longer than that achieved with prior anti-PD-1 monotherapy. Durable response was observed in an estimated 78% of patients who achieved CR at 24 months. After decitabine plus camrelizumab, the ratio increase of circulating peripheral central memory T cells directly correlated with both clinical response and progression-free survival. Conclusions: Decitabine plus camrelizumab is associated with high response rates and long-term benefits in patients with relapsed/refractory cHL who failed PD-1 inhibitors.

The current clinical outcome for patients with metastatic pancreatic carcinoma (PC) remains poor. Epidermal growth factor receptor (EGFR) is detectable in PC, suggesting that EGFR is a rational target in PC. We conducted a phase I clinical trial to evaluate the safety and efficacy of autologous anti-EGFR chimeric antigen receptor–modified T (CAR T–EGFR) cells in patients with metastatic PC. The expression levels of EGFR on tumor cells detected by immunohistochemistry were required to be more than 50%. Sixteen patients were enrolled and received one to three cycles of the CAR T–EGFR cell infusion within 6 months (median dose of CAR T cells: 3.48 × 106/kg; range, 1.31 to 8.9 × 106/kg) after the conditioning regimen with 100 to 200 mg/m2 nab-paclitaxel and 15 to 35 mg/kg cyclophosphamide. Grade ≥3 adverse events included fever/fatigue, nausea/vomiting, mucosal/cutaneous toxicities, pleural effusion and pulmonary interstitial exudation and were reversible. Of 14 evaluable patients, four achieved partial response for 2–4 months, and eight had stable disease for 2–4 months. The median progression-free survival was 3 months (range, 4–months) from the first cycle of CAR T–EGFR cell treatment, and the median overall survival of all 14 evaluable patients was 4.9 months (range, 2.9–30 months). Decreased EGFR expression on tumor cells was observed in patients who achieved stable disease with shrinkage of metastatic lesions in the liver, and enrichment of central memory T cells in infused cells improved the clinical response. In conclusion, the treatment with CAR T–EGFR cells is safe and effective in patients with metastatic PC. This trial was registered at www.clinicaltrials.gov (identifier no: NCT01869166).

COVID‐19 has developed into a worldwide pandemic; early identification of severe illness is critical for controlling it and improving the prognosis of patients with limited medical resources. The present study aimed to analyze the characteristics of severe COVID‐19 and identify biomarkers for differential diagnosis and prognosis prediction. In total, 27 consecutive patients with COVID‐19 and 75 patients with flu were retrospectively enrolled. Clinical parameters were collected from electronic medical records. The disease course was divided into four stages: initial, progression, peak, and recovery stages, according to computed tomography (CT) progress. to mild COVID‐19, the lymphocytes in the severe COVID‐19 progressively decreased at the progression and the peak stages, but rebound in the recovery stage. The levels of C‐reactive protein (CRP) in the severe group at the initial and progression stages were higher than those in the mild group. Correlation analysis showed that CRP (R = .62; P, Highlights Compared with COVID’19, Patients with flu had higher WBC and granulocyte. Lymphocyte progressively decreased in the progress of COVID’19. CRP level associated with CT scores and disease development of COVID’19. CRP increased at the initial stage of severe COVID’19, prior to CT findings. CRP showed good performance in prediction of severe COVID’19.

Purpose: To investigate the efficacy of a combination of montelukast and vitamins A and D drops in bronchial asthma children, and its effect on quality of life.Methods: Sixty bronchial asthma children from June 2018 to June 2020 were collected and randomized into study group and control group (30 cases in each group). Control group received montelukast sodium (chewable tablets), while the study group received vitamins A and D drops (capsules) plus. Clinical efficacy, lung function, serum inflammatory factors, and quality of life were evaluated and compared.Results: Compared with control group, total treatment effectiveness was higher and the symptom remission period was shorter in the study group (p < 0.05). Post-treatment, the parameters of FEV1 and FVC increased in both groups, but higher in the study group (p < 0.05). Serum levels of CRP and IL-4 in both groups decreased after treatment, while serum IL-10 levels were significantly up-regulated. Compared with control group, the levels of these indicators were improved in the study group (p < 0.05). Post-treatment Chinese Version of Pediatric Quality of Life Asthma Specific Scale (PedSQL) score was higher than before treatment, with higher values (for all indicators) in the study group (p < 0.05).Conclusion: The combination therapy of montelukast and vitamins A and D drops produces good clinical efficacy in children with bronchial asthma. It significantly shortens the time taken for relief of clinical symptoms, improves lung function, reduces inflammatory response, controls asthma, and improves the quality of life of the patients.

In Northwestern China, more and more traditional cultivation system (TC) with no mulching and flood irrigation have been replaced by modern cultivation technology (MC) combining plastic film mulching with drip irrigation. Does plastic film mulching increase or reduce soil CO

CD19-directed chimeric antigen receptor T cell (CART19) therapy is efficient and approved for relapsed/refractory diffuse large B cell lymphoma (DLBCL). To increase durable antitumor response, we previously designed tandem CART19/20 cells and shown longer progression-free survival. However, a proportion of CART19/20-treated patients will finally progress and require salvage therapies. In this study, we analyzed data from five patients with relapsed/refractory DLBCL who had disease progression or relapse following CART19/20 therapy and then treated with PD-1-blocking antibodies as salvage therapy. Two of five patients acquired complete remissions after anti-PD-1 therapy, including one patient remained ongoing remission for more than 21 months. One patient achieved a partial remission, and the other two had progressive diseases. No ≥ grade 3 treatment-related adverse events or cytokine release syndrome was observed. Immunohistochemistry of tumor specimens revealed higher PD-1/PD-L1 expression in responsive patients with anti-PD-1 therapy as compared to that in non-responders. After anti-PD-1 treatment, circulating T cells were activated in responders, and no significant expansion of CART19/20 cells was detected. Our data suggest that PD-1 blockade therapy can be active in patients with relapsed/refractory DLBCL after failure of CAR T cell therapy who had PD-L1 expression in tumor cells and high PD-1 level in tumor-infiltrated T cells. Supplementary Information The online version contains supplementary material available at 10.1186/s13045-021-01120-3.

The matter of energy waste has always been an unavoidable problem in the sustainable development of human beings. Because of poor awareness and weakness technology of environmental conservation, many classrooms and laboratories are very wasteful of power resources due to the use of traditional lighting systems. Focus on the problem that the traditional lighting control technology is used in the classroom lighting system. In this paper, a new intelligent lighting control system for the classroom is designed, based on PLC and industrial touch-sensitive screen. Firstly, a new intelligent lighting control system for the classroom based on PLC is presented according to the design ideas and the composition principle of typical electrical control system. There are three control modes: automatic, timing and manual, according to the needs of the classroom lighting system, Secondly, the lighting circuit and PLC control circuit are designed, in addition, the control principle of each component in the circuit is described in detail. Based on this, the control program of PLC is developed. The test results show that the system design is affordable, which can solve the above problems well.

Solar power is a typical source of green source and has a very near limitless supply. Not only having practical use now, but further study could lead to more potential. The solar energy water-heating technology is based upon energy conservation and the transformation of light into heat. Utilizing solar radiation power to constantly heat cold water, whilst storing it in hot water-saving tanks to benefit industries and daily life. In this paper, a measurement and control system water-temperature measurement and control system for solar water-heating engineering device based on programmable logic controller and industrial human-machine interface. First, S7-200 PLC is selected as the core controller, and Eview industrial touch-sensitive screen and Kingview monitoring software are used as the human-machine interface to design the hardware circuit. Second, the control program, Kingview monitoring interface and human-computer interaction interface of industrial touch-screen are compiled. The experimental results show that the scheme is reasonable and feasible, meets the design requirements, improves application performance and technical level of solar water-heating engineering device.

Recently, some global cases of 2019 novel coronavirus (COVID-19) pneumonia have been caused by second- or third-generation transmission of the viral infection, resulting in no traceable epidemiological history. Owing to the complications of COVID-19 pneumonia, the first symptom and imaging features of patients can be very atypical and early diagnosis of COVID-19 infections remains a challenge. It would aid radiologists and clinicians to be aware of the early atypical symptom and imaging features of the disease and contribute to the prevention of infected patients being missed.

Psoriasis is a chronic inflammatory skin disorder mediated by the cells and molecules of both the innate and adaptive immune systems. Autologous cytokine-induced killer (CIK) cell infusion is considered an effective and safe cancer treatment and is licensed for this use in China. Accumulated evidence indicating that CD3+CD56+ cells are significantly decreased in psoriatic patients prompted us to investigate if the restoration of CD3+CD56+ cells may be beneficial for psoriatic patients. We designed a clinical trial for psoriasis treatment that involved CIK cell infusion because CIK cells include a large amount of CD3+CD56+ T cells (NCT01894373 at www.clinicaltrials.gov). Six patients with severe psoriasis were initially enrolled, and four of them exhibited markedly lower levels of CD3+CD56+ cells in their peripheral blood (PB) relative to healthy donors. CIK cell infusion-associated toxicity was not observed in any infusion. The percentage of CD3+CD56+ cells in the PB markedly increased and the psoriasis area and severity index (PASI) synchronously decreased in four patients with lower CD3+CD56+ cell contents, and two of them obtained a more than 4-month PASI75 after completing a four-cycle treatment. However, a decrease in the CD3+CD56+ cells was observed concomitantly with disease recurrence after short-term amelioration. In contrast, no obvious improvement was observed in the two patients with nearly normal CD3+CD56+ cells in the PB before treatment. These observations suggest that the normalization of the CD3+CD56+ cell level may improve the skin lesions of severe psoriasis and warrant further clinical trials for severe psoriasis using repeated CIK adoptive immunotherapy.

Anti-CD19 chimeric antigen receptor-modified T (CAR-T-19) cells have emerged as a powerful targeted immunotherapy for B-cell lineage acute lymphoblastic leukemia with a remarkable clinical response in recent trials. Nonetheless, few data are available on the subsequent clinical monitoring and treatment of the patients, especially those with disease recurrence after CAR-T-19 cell infusion. Here, we analyzed three patients who survived after our phase I clinical trial and who were studied by means of biomarkers reflecting persistence of CAR-T-19 cells in vivo and predictive factors directing further treatment. One patient achieved 9-week sustained complete remission and subsequently received an allogeneic hematopoietic stem cell transplant. Another patient who showed relapse after 20 weeks without detectable leukemia in the cerebrospinal fluid after CAR-T-19 cell treatment was able to achieve a morphological remission under the influence of stand-alone low-dose chemotherapeutic agents. The third patient gradually developed extensive extramedullary involvement in tissues with scarce immune- cell infiltration during a long period of hematopoietic remission after CAR-T-19 cell therapy. Long-term and discontinuous increases in serum cytokines (mainly interleukin 6 and C-reactive protein) were identified in two patients (Nos. 1 and 6) even though only a low copy number of CAR molecules could be detected in their peripheral blood. This finding was suggestive of persistent functional activity of CAR-T-19 cells. Combined analyses of laboratory biomarkers with their clinical manifestations before and after salvage treatment showed that the persistent immunosurveillance mediated by CAR-T-19 cells would inevitably potentiate the leukemia-killing effectiveness of subsequent chemotherapy in patients who showed relapse after CAR-T-19-induced remission.

Current researches on cement hydration reaction are based on the isothermal or isobaric condition in laboratory. Regarding practical applications, a new model of cement hydration performance under a wide range of temperature and pressure is established considering the complicated interactions among the temperature, pressure and cement hydration reaction. The interactions include: transient change of temperature and pressure under the effect of cement hydration; variations of cement hydration performances with positions due to the distribution of temperature and pressure; transient change of cement hydration performances under the effect of transient temperature and pressure. In addition, the new model was validated through a field application, which demonstrates good agreement. Through numerical simulations, some of the most important hydration performance are analyzed including the degree of hydration, temperature, pressure, gel strength and chemical shrinkage. The models and conclusions in this paper can help troubleshoot performance problems and provide safety guidance during cement design.

Insufficient understanding of tip clearance on hydraulic and thrust performance is a major problem encountered in the design and application of the contra-rotating axial flow water-jet pumps. In order to investigate the effect of tip clearance on hydrodynamic and thrust characteristics of the pump, tip clearance coefficient [Formula: see text] is defined and scraping rate [Formula: see text] is introduced in this paper. Head coefficient and hydraulic efficiency are obtained with the numerical prediction and experiment as [Formula: see text], which are in good agreement with each other. With the increase of [Formula: see text], the saddle area of head coefficient slows down and the high efficiency zone narrows. Along the relative chord length of shroud of the rear rotor, the [Formula: see text] presents an opening down quadratic curve as [Formula: see text], and if [Formula: see text], it presents a “M” shape nearly. Comparing the two operating conditions of contra-rotating rotors and single rotor, the [Formula: see text] and wake effect of the rear rotor are enhanced and inhibited by the front rotor respectively for the interference between the two rotors, the thrust coefficient of the propulsion pump reaches the maximum when [Formula: see text].

Systemic inflammatory response syndrome (SIRS) was considered to play an important role in the progress of acute pancreatitis, but its specific relation with infected pancreatic necrosis remains largely unclear. We aimed to investigate the correlation between SIRS duration and infected pancreatic necrosis, and its application in prediction of infected pancreatic necrosis. A prospective observational cohort study of 2130 patients with acute pancreatitis from 2012 to 2017. The SIRS duration at the first week was registered daily, and demographic, radiology, and all clinical laboratory data were prospectively collected and retrospectively reviewed. A significant upward tendency of infected pancreatic necrosis incidence was observed with increased SIRS duration. In multivariate logistic regression, SIRS duration (odds ratio, 1.305; 95% CI, 1.161–1.468) was independently associated with infected pancreatic necrosis. ROC analysis demonstrated that the areas under curves of SIRS duration for predicting persistent multi-organ failure, pancreatic infection, and mortality were 0.97 (95% CI, 0.96–0.98), 0.92 (95% CI, 0.91–0.94), and 0.86 (95% CI, 0.83–0.90), respectively, which were comparable to, or even greater than, the area under curves of APACHE II and CT severity index scores. Early SIRS duration was strongly associated with infected pancreatic necrosis and could serve as an easy bedside indicator to predict pancreatic infection.

Psoriasis is a chronic inflammatory skin disorder mediated by the cells and molecules of both the innate and adaptive immune systems. Autologous cytokine-induced killer (CIK) cell infusion is considered an effective and safe cancer treatment and is licensed for this use in China. Accumulated evidence indicating that CD3

Adoptive immune cell transfer such as cytokine-induced killer (CIK) cells has become an important adjuvant approach in patients with tumours.The aim of this study was to analyse the adverse events (AEs) that occur during the transfusion of autologous CIK cells and to identify the risk factors associated with these AEs.Cell infusion-associated AEs were evaluated according to National Cancer Institute Common Terminology Criteria. Analysis was performed from a single-centre data on 893 malignant tumour patients who received a total of 4088 transfusions from March 2008 to October 2013.A total of 215/4088 (5.26%) transfusion cases from 893 patients presented with AEs (Grade 1 - 4); 204/215 (94.88%) were Grade 1 - 2, and 156/215 (72.56%) occurred within 24 h. The most common AEs were fever (0.88%), chills (0.56%) and fatigue (0.49%). The rare but severe AEs included anaphylactoid purpura, tumour lysis syndrome, anaphylactic shock, arthralgia. No transfusion-associated death was noticed. The mainly relative risk factors for AEs included transfer cycles and clinical stages.This study is a large-sample AEs research, to our knowledge, relative to immune cell transfusion from a single centre data analysis, revealing that autologous CIK cell therapy represents a fairly safe and well-tolerated treatment modality for malignant tumour patients, even rare severe, but not lethal AEs were observed in few patients.

Aberrant DNA methylation is one of the main drivers of tumor initiation and progression. The reversibility of methylation modulation makes it an attractive target for novel anticancer therapies. Clinical studies have demonstrated that high-dose decitabine, a hypomethylating agent, results in some clinical benefits in patients with refractory advanced tumors; however, they are extremely toxic. Low doses of decitabine minimize toxicity while potentially improving the targeted effects of DNA hypomethylation. Based on these mechanisms, low-dose decitabine combined with chemoimmunotherapy may be a new treatment option for patients with refractory advanced tumors. We proposed the regimen of low-dose decitabine-based chemoimmunotherapy for patients with refractory advanced solid tumors. A favorable adverse event profile was observed in our trial that was highlighted by the finding that most of these adverse events were grades 1-2. Besides, the activity of our cohort was optimistic and the clinical benefit rate was up to 60%, and the median PFS was prolonged compared with PFS to previous treatment. We also identified a significant correlation between the PFS to previous treatment and clinical response. The low-dose DAC decitabine-based chemoimmunotherapy might be a promising protocol for improving the specificity and efficiency of patients with refractory advanced solid tumors. This trial is registered in the ClinicalTrials.gov database (identifierNCT01799083).

Patients with relapsed or refractory non-Hodgkin lymphoma have a dismal prognosis. Chimeric Antigen Receptor (CAR)-modified T cells (CART cells) that targeted CD20 were effective in a phase I clinical trial for patients with advanced B-cell lymphomas. We performed a phase IIa trial to further assess the safety and efficacy of administering autologous anti-CD20 CART (CART-20) cells to patients with refractory or relapsed CD20+ B-cell lymphoma. Eleven patients were enrolled, and seven patients underwent cytoreductive chemotherapy to debulk the tumors and deplete the lymphocytes before receiving T-cell infusions. The overall objective response rate was 9 of 11 (81.8%), with 6 complete remissions (CRs) and 3 partial remissions; no severe toxicity was observed. The median progression-free survival lasted for >6 months, and 1 patient had a 27-month continuous CR. A significant inverse correlation between the levels of the CAR gene and disease recurrence or progression was observed. Clinically, the lesions in special sites, specifically the spleen and testicle, were refractory to CART-20 treatment. Collectively, these results together with our data from phase I strongly demonstrated the feasibility and efficacy of CART-20 treatment in lymphomas and suggest large-scale patient recruitment in a future study. This study was registered at www.clinicaltrials.org as NCT01735604.

The engineering of T lymphocytes to express chimeric antigen receptors (CARs) aims to establish T cell-mediated tumor immunity rapidly. In this study, we conducted a pilot clinical trial of autologous or donor- derived T cells genetically modified to express a CAR targeting the B-cell antigen CD19 harboring 4-1BB and the CD3ζ moiety. All enrolled patients had relapsed or chemotherapy-refractory B-cell lineage acute lymphocytic leukemia (B-ALL). Of the nine patients, six had definite extramedullary involvement, and the rate of overall survival at 18 weeks was 56%. One of the two patients who received conditioning chemotherapy achieved a three-month durable complete response with partial regression of extramedullary lesions. Four of seven patients who did not receive conditioning chemotherapy achieved dramatic regression or a mixed response in the haematopoietic system and extramedullary tissues for two to nine months. Grade 2–3 graft-versus-host disease (GVHD) was observed in two patients who received substantial donor-derived anti-CD19 CART (chimeric antigen receptor-modified T) cells 3–4 weeks after cell infusions. These results show for the first time that donor-derived anti-CD19 CART cells can cause GVHD and regression of extramedullary B-ALL. This study is registered at www.clinicaltrials.gov as NCT01864889.