Anlotinib in combination with Envolizumab plus Etoposide for the treatment of EX-SCLC:a case report

Background:Small cell lung cancer(SCLC)is an aggressive malignant tumor with strong immunosuppressive effects,characterized by rapid doubling time and poor prognosis.Currently,effective therapeutic options are urgently needed for Extensive-stage small-cell lung Cancer.Case description:In the present case,a combination therapy of anlotinib,envolizumab,and etoposide was administered to treat an 80-year-old female patient with extensive-stage SCLC accompanied by mediastinal lymph node and bone metastasis.After two cycles of treatment,the tumor lesions in the right lungs decreased from 5.04*3.44 cm to 1.65*1.42 cm.As of now,no significant mass is seen there and no serious adverse reactions in this patient.Until September 2023,she has survived for 18 months with no disease progression.Conclusions:Research shows that Alectinib,in combination with evolocumab plus etoposide,could be an original,viable therapeutic option for the treatment option of patients with extensive-stage SCLC.

Analysis of Commuting Modal Shift in Consideration of Social Interaction of Consciousness for Environment

It is the matter for achievement of the low carbon transport system that the excessive use of private vehicles can be controlled appropriately.Not only improvement of service level of modes except private vehicle,but also consciousness for environmental problem of individual trip maker is important for eco-commuting promotion.On the other hand,consciousness for environment would be changed by influence of other person.Accordingly,it is aimed in the study that the structure of decision-making process for modal shift to the eco-commuting mode in the local city is described considering environmental consciousness and social interaction.For the purpose,the consciousness for the environment problem and the travel behavior of the commuter at the suburban area in the local city are investigated by the questionnaire survey.The covariance structure about the eco-consciousness is analyzed with the database of the questionnaire survey by structural equation modeling.As the result,it can be confirmed with the structural equation model that the individual environmental consciousness is strongly related with the intention of self-sacrifice and is influenced with the local interaction of the individual connections.On the other hand,the intention of modal shift for the commuting mode is analyzed with the database of the questionnaire survey.It can be found out that the environmental consciousness is not statistically significant for commuting mode choice with the present poor level of service of public transport.However,the intention of self-sacrifice for the prevention of the global warming is statistically confirmed as the factor of modal shift with the operation of eco-commuting bus service with the RP/SP integrated estimation method.As the result,the multi-agent simulation system with social interaction model for eco consciousness is developed to measure the effect of the eco-commuting promotion.For the purpose,the carbon dioxide emission is estimated based on traffic demand and road network condition in the traffic environment model.On the other hand,the relation between agents is defined based on the small world network.The proposed multi-agent simulation is applied to measure the effect of the eco-commuting promotion such as improvement of level of service on the public transport or education of eco-consciousness.The effect of the promotion plan can be observed with the proposed multi-agent system.Finally,it can be concluded that the proposed multi-agent simulation with social interaction for eco-consciousness is useful for planning of eco-commuting promotion.

Envafolimab combined with chemotherapy in the treatment of combined small cell lung cancer: A case report

BACKGROUND Combined small cell lung cancer(C-SCLC) is a special subtype of small cell lung cancer that is relatively rare, aggressive, and prone to early metastasis and has a poor prognosis. Currently, there are limited studies on C-SCLC, and there is no uniform standard treatment, especially for extensive C-SCLC, which still faces great challenges. In recent years, the development and progress of immunotherapy have provided more possibilities for the treatment of C-SCLC. We used immunotherapy combined with first-line chemotherapy to treat extensive-stage C-SCLC to explore its antitumor activity and safety.CASE SUMMARY We report a case of C-SCLC that presented early with adrenal, rib, and mediastinal lymph node metastases. The patient received carboplatin and etoposide with concurrent initiation of envafolimab. After 6 cycles of chemotherapy, the lung lesion was significantly reduced, and the comprehensive efficacy evaluation showed a partial response. No serious drug-related adverse events occurred during the treatment, and the drug regimen was well tolerated.CONCLUSION Envafolimab combined with carboplatin and etoposide in the treatment of extensive-stage C-SCLC has preliminary antitumor activity and good safety and tolerability.

Combination of small interfering RNAs mediates greater suppression on hepatitis B virus cccDNA in HepG2.2.15 cells

AIM： To observe the inhibition of hepatitis B virus （HBV） replication and expression in HepG2.2.15 cells by combination of small interfering RNAs （siRNAs）. METHODS： Recombinant plasmid psiI-HBV was constructed and transfected into HepG2.2.15 cells. At 48 h, 72 h and 96 h after transfection, culture media were collected and cells were harvested for HBV replication assay. HBsAg and HBeAg in the cell culture medium were detected by enzyme-linked immunoadsorbent assay （ELISA）. Intracellular viral DNA and covalently closed circular DNA （cccDNA） were quantified by real-time polymerase chain reaction （PCR）. HBV viral mRNA was reverse transcribed and quantified by reverse-transcript PCR （RT-PCR）. RESULTS： siRNAs showed marked anti-HBV effects. siRNAs could specifically inhibit the expression of HBsAg and the replication of HBV DNA in a dosedependent manner. Furthermore, combination of siRNAs, compared with individual use of each siRNA, exerted a stronger inhibition on antigen expression and viral replication. More importantlycombination of siRNAs significantly suppressed HBV cccDNA amplification. CONCLUSION： Combination of siRNAs mediates a stronger inhibition on viral replication and antigenexpression in HepG2.2.15 cells, especially on cccDNA amplification.

Current situation and consideration of small splint in the treatment of distal radius fracture complicated with ulnar styloid process fracture

Objective:The incidence of distal radius fracture combined with ulnar styloid process fracture is increasing,which seriously affects the quality of life of patients.Small splint therapy of Traditional Chinese Medicine is a reliable method for the treatment of such fractures.It not only has good clinical efficacy,but also has fewer complications and high safety.However,the traditional small splint fixation does not cover the styloid process of the ulna,and the fracture of the styloid process of the ulna is closely related to the stability of the wrist joint,which has an important impact on the prognosis of the fracture.Based on this,we believe that the ulnar elongation splint can better improve the wrist function,and further prospects for related issues,in order to guide clinical practice.

Improved Circularity Metrology of Small Cylindrical Workpieces by the Segmenting-stitching Technique

To address the alignment and measuring force problem in the segmenting-stitching technique for the circularity metrology of small cylindrical workpieces(diameter less than 1.5 mm and length less than 10 mm),a magnet combination jig method is proposed.A small round magnet is attached between the round magnetic jig and small cylinder,and the other end of the small cylindrical workpiece is attached to some cylindrical magnets.Thus,the smaller cylinder can be put in the V-groove and measured successfully with the magnet combination.For verifying the advantage of the magnet combination jig,four measurement quality evaluations are proposed:the circumferential deviation of neighbor arc contours,radial deviation of neighbor arc contours,angle of inclination between the V-groove and small cylinder,and curvature of the obtained arc.The results show that the matching coefficient is enhanced by 98%,the Euclidean distance of overlap parts of neighbor arc contours is reduced by 68%,the position error is reduced 27%,and the average curvature of the arc contours is improved.It can be concluded that the measuring quality can be enhanced prominently by this magnet combination method for the segmenting-stitching method.

Better to be alone than in bad company:The antagonistic effect of cisplatin and crizotinib combination therapy in non-small cell lung cancer

AIM To investigate the potential benefit of combining the cMET inhibitor crizotinib and cisplatin we performed in vitro combination studies.METHODS We tested three different treatment schemes in four non-small cell lung cancer(NSCLC) cell lines with a different cMET/epidermal growth factor receptor genetic background by means of the sulforhodamine B assay and performed analysis with Calcusyn.RESULTS All treatment schemes showed an antagonistic effect in all cell lines,independent of the cMET status.Despite their different genetic backgrounds,all cell lines(EBC-1,HCC827,H1975 and LUDLU-1) showed antagonistic combination indexes ranging from 1.3-2.7.These results were independent of the treatment schedule.CONCLUSION These results discourage further efforts to combine cMET inhibition with cisplatin chemotherapy in NSCLC.

Analysis of Key Technologies in the Design of Small and Medium Span Basket Type Steel Box Tied Arch Bridge

In order to ensure the construction quality and safety of small and medium span basket type steel box tied arch bridge,this paper takes a practical project as an example to analyze the key technologies in its design process.It is hoped that this analysis can provide corresponding reference for the design and construction of this kind of arch bridge.

Further understanding of an uncommon disease of combined small cell lung cancer： clinical features and prognostic factors of 114 cases

Objective： Combined small cell lung cancer （C-SCLC） is an uncommon subgroup of small cell lung cancer （SCLC） and few clinical data can be referred. Our study is to investigate the clinical features and prognostic factors of C-SCLC, as well as the role of multimodality treatment.Methods： Between January 2004 and December 2012, patients with histologically diagnosed C-SCLC were retrospectively analyzed. The survivals were evaluated with the Kaplan-Meier method. Univariate and multivariate analyses were used to evaluate potential prognostic factors.Results： One hundred and fourteen patients were enrolled, with a median age of 59 （range： 20-79） years old. The most common combined component was squamous cell carcinoma （52.6%）. Among these patients, the disease was stage I, II, III and IV in 9.6%, 19.3%, 46.5% and 24.6% of the patients, respectively. Eighty patients （70.2%） received at least two of the three modalities containing chemotherapy, radiotherapy and surgery. The median follow-up was 32.5 months. The median time of overall survival （OS） was 26.2 months. On univariate analysis, smoking （P=0.029）, Karnofsky performance score （KPS） 〈80 （P=0.000）, advanced TNM stage （P=0.000）, no surgery （P=0.010）, positive resection margin （P=0.000）, positive lymph nodes ≥4 （P=0.000）, positive lymph node ratio 〉10% （P=0.000） and non-multimodality treatment （P=0.004） were associated with poor OS. Multivariate analysis confirmed that smoking, advanced TNM stage, positive resection margin and positive lymph nodes ratio 〉 10% were poor prognostic features. Conclusions： C-SCLC has a relatively early stage and good prognosis, which may due to the underestimated diagnosis in non-surgical patients. Multimodality therapy is recommended, especially for limited disease. Smoking, advanced TNM stage, positive resection margin and positive lymph nodes ratio 〉10% are poor prognostic factors.

Life prediction and test period optimization research based on small sample reliability test of hydraulic pumps

Hydraulic pumps belong to reliable long-life hydraulic components. The reliability evaluation includes characters such as long test period,high cost,and high power loss and so on. Based on the principle of energy-saving and power recovery,a small sample hydraulic pump reliability test rig is built,and the service life of hydraulic pump is predicted,and then the sampling period of reliability test is optimized. On the basis of considering the performance degradation mechanism of hydraulic pump,the feature information of degradation distribution of hydraulic pump volumetric efficiency during the test is collected,so an optimal degradation path model of feature information is selected from the aspect of fitting accuracy,and pseudo life data are obtained. Then a small sample reliability test of period constrained optimization search strategy for hydraulic pump is constructed to solve the optimization problem of the test sampling period and tightening end threshold,and it is verified that the accuracy of the minimum sampling period by the non-parametric hypothes is tested. Simulation result shows it could possess instructional significance and referenced value for hydraulic pump reliability life evaluation and the test's research and design.

Enzymes activity of intestinal grafts after liver small bowel transplantation in rats

OBJECTIVES: To investigate the activity alterations of enzymes in intestine grafts after liver/small bowel transplantation in rats and the relations of these changes to immune rejection of grafts. METHODS: A model of liver/small bowel transplantation (LSBT) was established in closed colony SD and Wistar rats. The activity of enzymes including triphosphatase (ATPase), alkalinophosphatase (AKP), acytelcholinesterase (AchE), oxidesynthase (NOS) and monoamine oxidase (MAO) in bowel grafts was studied histochemically at regular postoperative intervals. RESULTS: The activity of enzymes in the wall of the grafts disappeared eventually in isolated small bowel transplantation (SBT) rats. In contrast, the activity in LSBT rats remained and recovered postoperatively. CONCLUSIONS: The rejection in grafted intestine could be prevented or delayed in LSBT rats. The changes in the activity of enzymes and neurons might be used to detect the rejection and function of the graft.

Misdiagnosis of ligamentoid fibromatosis of the small mesenteric:A case report

BACKGROUND Ligamentoid fibromatosis is a rare borderline tumor that occurs in the muscles,fascia,and aponeurosis.It is a kind of soft tissue tumor of fibrous origin,also known as invasive fibromatosis,desmoid fibroma,neurofibromatosis,etc.The tumor is between benign and malignant tumors and rarely has distant metastasis.Its characteristics are mainly local invasion,destruction and growth and easy recurrence.The World Health Organization defines it as a fibroblast cloning value-added lesion originating from deep soft tissue,which causes local invasion and growth leading to tissue reconstruction,extrusion and destruction of important structures and organs.The incidence rate accounts for 0.03%of all tumors and less than 3%of all soft tissue tumors.Definite diagnosis mainly depends on postoperative pathology.Surgical resection is still the main way to treat the disease,and a variety of nonsurgical treatment methods are auxiliary.Combined treatment can effectively reduce the risk of postoperative recurrence.CASE SUMMARY The patient is a 57-year-old female.One week ago,she accidentally found a mass in the left upper abdomen while lying flat.There was no abdominal pain and abdominal distention,no fever,no black stool and blood in the stool and no nausea and vomiting.She had a 10-year history of glaucoma on the left side,underwent hysterectomy for uterine fibroids 5 years ago,had no hypertension,heart disease,diabetes,hepatitis or tuberculosis,had no history of smoking and had been drinking for 20 years.CONCLUSION Accurate preoperative diagnosis is difficult,surgical resection is the main treatment,and a variety of nonsurgical treatment methods are auxiliary.Combined treatment can effectively reduce the risk of postoperative recurrence.The prognosis is still good,and the risk of recurrence of secondary surgery is greatly increased.

Adjuvant Chemotherapy of Gemcitabine plus Carboplatin versus Paclitaxel plus Carboplatin in Patients with Resected Non-Small Cell Lung Cancer

Background: This retrospective study was to evaluate the efficacy and toxicity of gemcitabine plus carboplatin (GC regimen) and paclitaxel plus carboplatin (PC regimen) combination chemotherapy administered as an adjuvant therapy after complete resection of non-small cell lung cancer. Methods: Forty-four patients (GC regimen, n = 29;PC regimen, n = 15) received gemcitabine at a dose of 1000 mg/m2 on days 1 and 8, and carboplatin with the target dose of area under the curve (AUC) of 4 on day 8 every 28 days and paclitaxel at a dose of 70 mg/m2 on days 1, 8 and 15, and carboplatin with the target dose of AUC of 5 on day 1 every 28 days. Results: A total of 130 cycles of the treatment were administered (averaged, 3.1 in GC arm and 2.7 cycles in PC arm). Forty-three patients (97.7%) completed the scheduled cycles. One patient (2.3%) was discontinued due to grade 4 pneumonia. The dose was reduced in 2 patients (4.5%) due to grade 4 thrombocytopenia. Grade 3/4 neutropenia was significantly observed in the PC group (GC: 12/29, 41.4%;PC: 11/15, 73.3%, p = 0.0443). The nonhematological toxicities were mild. Grade 1/2 alanine aminotransferase and aspartate aminotransferase in the GC group was significantly observed higher compared to those of the PC group (GC: 20/29, 69.0%;PC: 4/15, 26.7%, p = 0.0076). Grade 1/2 alopecia was significantly observed in the PC group (GC: 0/25, 0.0%;PC: 13/15, 86.7%, p 0.0001). There was no treatment-related death. The median survival time (MST) of the entire GC group was 784 days, the 3-year overall survival (OS) was 75.9%, and 3-year recurrence-free survival (RFS) was 65.5%. The MST of the entire PC group was 963 days, the 3-year OS was 80.0%, and the 3-year RFS was 60.0%. Conclusion: These results demonstrate that the GC and PC combination chemotherapies are efficacious and feasible regimens, which should be considered as one of the standard therapies for adjuvant therapy.

Full scale application of combined SBF-AS process for municipal wastewater treatment in small towns and cities in China

The combined submerged biofilm （ SBF）-activated sludge （AS） process for treatment of municipal wastewater in a small city in China is described in this paper. The process exhibited high removal efficiencies for carbonaceous substances, nitrogen and phosphorus which mainly took place in the combined SBF-AS biore- actor. The SBF-AS bioreactor was divided into pre-anoxic, anaerobic, anoxic and aerobic zones from inlet to outlet, in which fixed biofilm carriers were packed. Excellent performance had been obtained under normal operating conditions in more than one year of operation in Dong＇ e municipal WWTP, Shandong province, with mean removal efficiencies of BOD5 93.4%, COD 88%, SS 92%, NH4 - N 82. 1%, TP 75% and TN 66.7%, and quite high effluent quality such as BOD5 6 to 10 rag/L, COD 20 to 40 rag/L, SS 5 to 10 rag/L, TN 10 to 20 rag/L, NH4 - N 4 to 8 mg/L and TP 0. 6 to 1.0 mg/L. The effluent was reused multi-purposely, such as toilet flushing, green belt watering and artificial lake pounding. Simultaneous nitrification and denitrification took place due to the DO gradient in biofilm in aerobic zone of the SBF-AS bioreactor, which made TN removal efficiency improved remarkably in system. Some activated sludge was returned from final clarifiers to the bioreactor for phosphorus removal. The process had the advantages of low investment and low operational/ maintenance （O/M） costs, low sludge yield and was preferably employed in small towns and cities.

Effect of TCM Combined with Chemotherapy on Immune Function and Quality of Life of Patients with Non-small Cell Lung Cancer inStage Ⅲ-Ⅳ

Objective: To observe and compare the effect of traditional Chinese medicine (TCM) combined with chemotherapy (CT) on immune function and quality of life (QOL)of patients with non-small cell lung cancer (NSCLC) in stage Ⅲ-Ⅳ. Methods: One hundred cases with stage Ⅲ-Ⅳ NSCLC were randomly divided into two groups. The treated group (n=50) received CT combined with TCM, and the control group received CT alone. The percentage of T lymphocyte subset in peripheral blood and the change of natural killer (NK) cell count were observed after treatment. The QOL and tolerance of CT were also compared between the two groups after treatment. Results: In the treated group, CD3 cell count, CD4 cell count, CD4/ CDg ratio and NK cell activity were higher than those in control group, while CD8 cell count in the treated group was lower than that in the control group (P<0.05), and QOL and tolerance of CT in the treated group were also better (P<0.05). Conclusion: TCM combined with CT could raise the patients' ability in tolerating CT in stage Ⅲ-ⅣNSCLC.

The efficacy of TKIs in treatment of human primary small cell lung cancer xenograft model in vivo

Objective: To study the treatmaient of non-small cell lung cancer, we established the HU-Prim allograft transplantation tumor model. Methods: The fresh tumor samples were transplanted in the right scapular subcutaneous layer of the severe combined immunodeficient Non-obese diabetic/severe combined immunodeficient(NOD/SCID) mice. The pathological features of the tumors were observed. Nonnecrotic tissue was inoculated subcutaneously into the right axillary. When the tumor in burdened rat grew approximately 100 mm3, according to the tumor size all the animals were divided into the following four groups, eight rats in each group: solvent control group, gefitinib group(100 mg/kg), erlotinib group(50 mg/kg), afatinib group(20 mg/kg). Aniamals were treated with drugs by intragastric(i.g.) administrated, once daily, for consecutively 14 days. Measure the tumor size 2-3 times every week. Results: Hu Prime1-NSCLC mutant sensitive xenograft model research data showed that reversible tyrosine kinase inhibitors gefitinib, erlotinib and irreversible tyrosine kinase inhibitor afatinib could effectively inhibit tumor growth in EGFR positive NSCLC allografts model. The pharmacodynamic activity of irreversible inhibitor was better than that of the reversible inhibitor. Specimens from clinical anthropogenic tumor retain characteristics of the human primary malignancy, histopathology, biological characteristics, and tumor markers, etc., which can more accurately reflect the characteristics of the tumor and the impact of interventions. Conclusion: The model is not only a good antitumor drug experimental platform, but also a new evaluation tool of individualized medication.

STUDY ON THE SMALL CRACKS OF COVER STRATA AFTER THE COMBINED MINING IN THE THIN SEAMS

By using the continuous exploration system with multi-pipeline in the borehole, the failure cracks of cover strata (specially, the small cracks developing) after the combined mining of 16, 17 thin seams of the 4th mining block in Zhaopo Mine is explored. After that, the researching result is considered as the output and the testing result of rock mechanics parameters is considered as the verifying data, the back analysis is made with the conception of the point safety degree. The relative height of the crack developing is obtaied. So, the evaluating of the safety of 16, 17 seams combined mining under the gob water with extreme distance is made and the mining has been safety. The scientific basis is provided for the evaluating of the mining safety with the similar conditions.

奥希替尼联合培美曲塞/铂类对表皮生长因子受体合并TP53基因突变的非小细胞肺癌疗效及预后分析

目的探究奥希替尼联合培美曲塞/铂类对EGFR合并TP53突变的非小细胞肺癌(NSCLC)疗效及预后分析。方法选取中国人民解放军联勤保障部队第904医院在2016年1月至2022年6月间诊治的80例表皮生长因子受体合并TP53基因突变的NSCLC患者纳入本次研究,随机数字法分为对照组(40例)和研究组(40例)。对照组行奥希替尼治疗,研究组行奥希替尼联合培美曲塞/铂类化疗治疗。对两组临床疗效、血清指标水平、用药安全性以及预后进行对比分析。结果研究组总缓解率(ORR)和疾病控制率(DCR)均优于对照组(P<0.05)。治疗后,两组细胞角蛋白19片段(CYFRA21-1)、癌胚抗原(CEA)水平均低于治疗前(P<0.05),研究组低于对照组(P<0.05)。治疗后,两组白细胞介素4(IL-4)、血管内皮生长因子(VEGF)、细胞间黏附分子-1(ICAM-1)水平均低于治疗前(P<0.05),研究组低于对照组(P<0.05)。两组不良反应差异无统计学意义(P>0.05)。研究组随访1年后的生存率明显高于对照组(P<0.05)。治疗后,两组生存质量测定表(EORTC QLQ-C30)评分高于治疗前(P<0.05),研究组高于对照组(P<0.05)。结论奥希替尼联合培美曲塞/铂类化疗方案用于EGFR合并TP53基因突变的NSCLC的临床治疗,可有效发挥抗肿瘤效果,下调炎症水平,提升疗效,改善患者预后,且用药具有较高安全性,不会明显增加不良反应。

超长大跨度公铁合建桥梁结构体系研究

新建甬舟铁路西堠门公铁两用大桥连接金塘岛和册子岛,桥位处海域宽2.7 km,最大水深93 m,地形复杂,桥梁设计难度大。为研究超长大跨度公铁合建桥梁合理结构体系,结合地形地质条件,选取主跨1500 m悬索桥、斜拉桥及斜拉悬索协作体系3种桥型方案,对上部结构设计进行详细介绍,并从静力性能、动力性能、经济性能等方面对不同结构体系进行对比分析。研究表明:(1)与斜拉体系相比,协作体系桥可减小30%~50%的主梁内力和60%的桥塔内力,一定程度上解决了加劲梁承受巨大轴压力造成屈曲问题,并有效减小了桥塔规模;(2)与悬索桥相比,协作体系可减小50%的主缆内力,主缆钢丝和锚碇的工程量相应减小,施工难度得以降低,同时协作体系扭转频率更高,降低了结构在较低风速下发生涡激振动的可能性;(3)斜拉悬索协作体系能够充分发挥斜拉结构和悬索结构的组合优势,实现超大跨度的同时具有较大的纵向刚度和竖向刚度,满足铁路行车对结构刚度的要求;(4)对于主跨1500 m级超长大跨度公铁合建桥梁,斜拉悬索协作体系经济性更好。

组合光透视下小面积室内封闭空间分割方法

为提高室内空间的优化规划设计能力,提出基于点云数据语义分割的组合光透视下小面积室内封闭空间分割方法。构建小面积室内封闭空间的环境三维信息感知模型,采用室内空间点云提取室内封闭空间图像的坐标信息,结合语义组合特征分割方法将融合空间信息映射到高分辨空间异质单元结构中,引入几何约束的子空间投影特征信息,结合组合光透视的高分辨率分割图模型参数融合方法,提取小面积室内封闭的端元,采用点云数据语义分割方法实现空间分割。结果表明,采用该方法有效实现对复杂室内场景的三维重建,空间分割的均方根误差较低为0.808%,峰值信噪比较高42.156 dB,空间分割速度较快,平均为12.83 ms。