Objective:To investigate the efficacy and safety of anlotinib combined with gemcitabine + cisplatin (GP) regimen in the treatment of patients with recurrent or metastatic nasopharyngeal carcinoma.Methods:A retrospective case controlled study was conducted. The clinical data of 82 patients with nasopharyngeal carcinoma newly diagnosed as distant metastasis or recurrence and metastasis after radical chemoradiotherapy in the Second Affiliated Hospital of Guangxi University of Science and Technology and Laibin People's Hospital from January 2020 to December 2021 were retrospectively analyzed. Among 82 patients, 45 patients receiving anlotinib combined with GP regimen were treated as the treatment group, and 37 patients receiving GP chemotherapy regimen during the same period were treated as the control group. Short-term efficacy and adverse reactions were compared between the 2 groups. Kaplan-Meier method was used to compare the progression-free survival (PFS) and overall survival (OS), and log-rank test was performed. Cox proportional risk model was used to analyze the factors influencing the PFS of patients.Results:Among 82 patients, 63 were males and 19 were females, aged (48±10) years. The objective response rate (ORR) and disease control rate (DCR) in the treatment group were higher than those in the control group [ORR: 71.11% (32/45) vs. 62.16% (23/37); DCR: 86.67% (39/45) vs. 81.08% (30/37)], while there were no statistically significant differences (all P > 0.05). The median PFS time was 23.53 months (95% CI: 17.48-29.58 months), 17.40 months (95% CI: 13.33-21.47 months), respectively in the treatment group and the control group, and the difference in PFS was statistically significant ( P < 0.05). The median OS time was 34.03 months (95% CI: 29.42-38.64 months), 30.47 months (95% CI: 28.28-32.66 months), respectively in the treatment group and the control group, and the difference in OS was not statistically significant ( P > 0.05). Oral anlotinib, recurrence or metastasis at initial diagnosis were independent factors influencing the PFS of patients. The main adverse effects of anrotinib were grade 1-2 anorexia, fatigue, granulocytopenia, hypertension, hand-foot syndrome, oral mucositis, and liver function damage. The incidence of grade 3-4 was low, and the adverse reactions in most patients could be controlled after symptomatic treatment and adjustment of drug dosage. Conclusions:For patients with recurrent or metastatic nasopharyngeal carcinoma, oral anlotinib targeted therapy combined with GP chemotherapy regimen can prolong the PFS time of patients. Most anlotinib-related side effects can be tolerated.Objective To investigate the efficacy and safety of anlotinib combined with gemcitabine + cisplatin (GP) regimen in the treatment of patients with recurrent or metastatic nasopharyngeal carcinoma. Methods A retrospective case controlled study was conducted. The clinical data of 82 patients with nasopharyngeal carcinoma newly diagnosed as distant metastasis or recurrence and metastasis after radical chemoradiotherapy in the Second Affiliated Hospital of Guangxi University of Science and Technology and Laibin People's Hospital from January 2020 to December 2021 were retrospectively analyzed. Among 82 patients, 45 patients receiving anlotinib combined with GP regimen were treated as the treatment group, and 37 patients receiving GP chemotherapy regimen during the same period were treated as the control group. Short-term efficacy and adverse reactions were compared between the 2 groups. Kaplan-Meier method was used to compare the progression-free survival (PFS) and overall survival (OS), and log-rank test was performed. Cox proportional risk model was used to analyze the factors influencing the PFS of patients. Results Among 82 patients, 63 were males and 19 were females, aged (48±10) years. The objective response rate (ORR) and disease control rate (DCR) in the treatment group were higher than those in the control group [ORR: 71.11% (32/45) vs. 62.16% (23/37); DCR: 86.67% (39/45) vs. 81.08% (30/37)], while there were no statistically significant differences (all P > 0.05). The median PFS time was 23.53 months (95% CI: 17.48-29.58 months), 17.40 months (95% CI: 13.33-21.47 months), respectively in the treatment group and the control group, and the difference in PFS was statistically significant ( P < 0.05). The median OS time was 34.03 months (95% CI: 29.42-38.64 months), 30.47 months (95% CI: 28.28-32.66 months), respectively in the treatment group and the control group, and the difference in OS was not statistically significant ( P > 0.05). Oral anlotinib, recurrence or metastasis at initial diagnosis were independent factors influencing the PFS of patients. The main adverse effects of anrotinib were grade 1-2 anorexia, fatigue, granulocytopenia, hypertension, hand-foot syndrome, oral mucositis, and liver function damage. The incidence of grade 3-4 was low, and the adverse reactions in most patients could be controlled after symptomatic treatment and adjustment of drug dosage. Conclusions For patients with recurrent or metastatic nasopharyngeal carcinoma, oral anlotinib targeted therapy combined with GP chemotherapy regimen can prolong the PFS time of patients. Most anlotinib-related side effects can be tolerated.

Objective To explore the effect and related mechanism of Zuogui Jiangtang Jieyu Prescription on neuroinflammation of nucleus accumbens in rats with diabetes mellitus(DM)complicated with depression based on dopamine receptor.Methods DM,depression and DM complicated with depression models were respectively established through a combination of high-fat feeding and streptozotocin intraperitoneal injection,as well as chronic unpredictable mild stress+solitary cage feeding.The rats were divided into control group,depression group,DM group,DM complicated with depression group,positive group,D1R agonists group,D2/3R agonists group and Zuogui Jiangtang Jieyu Prescription group.Depression and learning and memory abilities in rats were assessed using open field experiments,forced swimming experiments and water maze experiments.Neuronal damage in nucleus accumbens was detected through HE and Nissl staining.Serum contents of 5-hydroxytryptamine(5-HT),dopamine(DA),interleukin(IL)-1β and IL-18 were detected by ELISA.The expressions of D1R,D2R,D3R and Iba1/NLRP3 in nucleus accumbens were detected by immunofluorescence.The protein expressions of D1R,D2R,D3R,NLRP3,ASC,Caspase-1 p20 and IL-1β in nucleus accumbens were detected by Western blot.Results Compared with the control group,the changes of fasting blood glucose(FBG)in rats of DM complicated with depression group significantly increased(P<0.01),the total distance and number of activities in the open field experiment,the time ratio of staying in the original platform quadrant and the number of times crossed the original platform in the water maze experiment significantly decreased(P<0.05,P<0.01),the forced swimming immobility time and the escape latency period in the water maze experiment were prolonged(P<0.05,P<0.01),the contents of serum 5-HT and DA significantly decreased(P<0.01),the contents of IL-1β and IL-18 significantly increased(P<0.05,P<0.01),neurons in the nucleus accumbens showed nuclear condensation,degeneration,and increased necrotic cells,with loss of Nissl bodies,the expressions of D1R,D2R and D3R were significantly decreased(P<0.01),while the expressions of NLRP3,ASC,Caspase-1 p20 and IL-1β protein significantly increased(P<0.05,P<0.01).Compared with the DM complicated with depression group,the changes of FBG significantly decreased in the Zuogui Jiangtang Jieyu Prescription group,learning and memory abilities were enhanced,depression-like behavior was improved,and the damage to neurons in the nucleus accumbens was reduced,the contents of serum 5-HT and DA significantly increased(P<0.01),the contents of IL-1β and IL-18 significantly decreased(P<0.01),the expressions of D1R,D2R and D3R in the nucleus accumbens increased(P<0.05,P<0.01),and the expressions of NLRP3,ASC,Caspase-1 p20 and IL-1β protein decreased(P<0.05,P<0.01).Conclusion The dopaminergic system dysfunction and neuroinflammation are the key mechanisms of DM complicated with depression.Zuogui Jiangtang Jieyu Prescription may improve neuroinflammation by regulating the dopamine receptor to inhibit the activation of microglial NLRP3 signaling in the nucleus accumbens.

Objective:To prepare a novel tri-specific T cell engager (19TriTE) targeting CD19 antigen, and to investigate its immunotherapeutic effect on CD19-positive hematological malignancies.Methods:19TriTE was constructed by molecular cloning technology and successfully expressed through the eukaryotic expressing system. The effects of 19TriTE on the proliferation and activation of T cells, as well as the specific cytotoxicity against CD19 positive tumor cell lines were verified.Results:①19TriTE expressing plasmid was constructed and successfully expressed through the eukaryotic expressing system. ②19TriTE can specifically bind to T cells and Nalm6 cells, with equilibrium dissociation constants of 19.21 nmol/L and 11.67 nmol/L, respectively. ③The expression rates of CD69 positive T cells and CD25 positive T cells were 35.4% and 49.8% respectively, when 2 nmol/L 19TriTE were added in the co-culture system, which were significantly higher than those in the control group. ④19TriTE can significantly promote the proliferation of T cells. The absolute count of T cells expanded from the initial one million to 74 million with an 74 fold increase at the concentration of 1 nmol/L on day 12. ⑤19TriTE can significantly mediate T cells killing of CD19 positive target cells in a dose-dependent manner. At the concentration of 10 nmol/L, the target cells lysis reached 50%. ⑥Degranulation experiment verified that 19TriTE can activate T cells in the presence of CD19 positive target cells, and the activation of T cells positively correlated with the dose of 19TriTE. ⑦When 19TriTE fusion protein co-cultured with T cells and target cells overexpression RFP and luciferase genes respectively, 19TriTE can notably mediate T cells killing of CD19 positive target cells through fluorescent microscope or bioluminescence imaging technology.Conclusion:In this study, we successfully constructed and expressed 19TriTE fusion protein and verified that it can effectively activate T cells and promote their proliferation in vitro. At the same time, it can bind to CD19 positive target cells and T cells, as well as enhance T cells anti-leukemia effect in vitro, providing the foundation for further clinical research.

Ear and upper airway are portal organs of human body. Because of their fine and narrow structure, the non-invasive research and the effect of clinical diagnosis and treatment in traditional medicine are always unsatisfactory. With the development of computer technology, numerical simulation has become an effective means of auxiliary research. Numerical simulation can reproduce or evaluate the diagnosis and treatment of ear and upper airway diseases, and it is a powerful means to promote the development of basic medicine and technology of clinical diagnosis and treatment. The application of numerical simulation in relationship between the structure and function of ear and upper airway, the influence of diseases on function, the evaluation of clinical diagnosis and treatment technology， as well as the design of related medical devices were reviewed. The clinical application of numerical research in ear and upper airway was prospected, so as to provide references for the future clinical diagnosis and treatment of ear and upper airway.

Objective To observe the effect of rhubarb enema on serum level of high mobility group protein B1 (HMGB1) in patients with severe acute pancreatitis (SAP).Methods A total of 60 cases of patients with SAP in our hospital were collected from October 2014 to October 2016,and were randomly divided into the observation group and control group (30 cases in each group).Serum levels of HMGB1 were dynamically detected on the 1st,3rd and 5th day after admission.The acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) was conducted.The recovery time of gastrointestinal function and time for continuous renal replacement therapy (CRRT) were observed.Results On the 1st day after admission,no statistically significant difference was found in serum level of HMGB1 between the two groups (P＞0.05).The serum level of HMGB1 in the observation group was obviously decreased on the 5th day after admission,which was lower than that in the control group,there was statistically significant difference(P＜0.05).In the observation group,the value of difference between serum level of HMGB1 on the 1st day after admission and that on the 3rd day after admission was significantly negatively related with the APACHE Ⅱ score on the 3rd day after admission(r=-0.604,P＜0.05).In the observation group,the remission time of abdominal pain and abdominal distension,first time of exhaust and defecation and time for CRRT were significantly shorter than those in the control group,there were statistically significant differences (P＜0.05).Conclusion Rhubarb could improvesymptoms and prognosis of patients with SAP through effectively inhibit the expression of HMGB1.

[ABSTRACT]OBJECTIVETo study the deposition of suspended particles in the respiratory tract during human breathing.METHODSBased on CT data, three dimensional finite element model of an anatomically accurate respiratory tract, including the nasal cavity, oral cavity, pharynx, larynx, trachea and parts of tracheobronchial tree, is established. Numerical analysis for the deposition of suspended particles in the respiratory tract was conducted. RESULTSThe velocity and pressure distributions of airflow in the respiratory tract were obtained, as well as the particles path and their deposition law.CONCLUSION Respiratory tract plays an important role in filtering suspended particles in the air during breathing. The main deposition sites of the particles were at the front of the inferior turbinate and the posterior pharyngeal wall.

Objective To analyze the airflow characteristics and investigate the relationship of the structure and the function of nasal cavity by the three?dimensional reconstruction of nasal airway of patients with structural abnormalities(nasal septum deviation)and healthy people and the estab?lishment of finite element model by computer. Methods On the basis of CT imaging of the nasal cavity in patients with structural abnormalities(na?sal septum deviation,n=20)and healthy people(n=20),three?dimensional reconstruction of nasal airway was conducted by resurfacing finite ele?ment subdivision to simulate the characteristics of airflow in nasal cavity. Results The airflow mainly went through the commodious side of the nose in patients with nasal septum deviation and the maximum fluence appeared in the middle part of meatus nasi communis. The airway pressure de?creased most significantly in the most flank?curvature part of nasal septum deviation,accounting approximately 79.65%of the total pressure. In healthy people,the bilateral airflow was affected by nasal cycle and was mainly characterized by one nasal cavity,and the maximum fluence was ob?served in the middle and the inferior part of meatus nasi communis. The airway pressure decreased most significantly in limen nasi,accounting ap?proximately 58.78%of the total pressure. Conclusion Numerical modeling of nasal cavity can be used to analyze the relationship between the nasal structural abnormalities and the airflow characteristics,which is a scientific method to analyze the association of nasal structure and function with dis?ease and can be used for pre?and post?operative individual evaluation of operative therapeutic regimen targeting at optimizing airway and altering air?flow distribution.

[ABSTRACT]OBJECTIVETo explore the basic characters of the airflow-field in Chinese people's nasal cavity by computational fluid dynamics.METHODSThe three-dimensional, finite-element mesh were developed from Spiral CT imaging scans of nose of the 40 healthy Chinese people. Given the following spatial boundaries of the flow field: no-slip condition was imposed at the surface of the nasal airway walls; a standard atmosphere pressure condition was established at the inlet; a velocity vector was specified at the outlet (nasopharynx), which was obtained under the condition of aspiratory flow rate (12 L/min), the full Navier-Stokes and continuity equations were solved to obtain the airflow pattern.RESULTS1. The airflow passed mainly through left or right side of the nasal airway in the whole 40 cases (left 33, right 7),and the volume of air through the main-side is (320±28) ml while non-main-side (180±45) ml. 2. Airflow velocity: airflow of anterior nostrils, internal nostrils, the middle and inferior parts of the total meatus in the main-side were (5.01±2.12) m/s, (7.00±1.75) m/s, (5.08±1.55) m/s, (4.12±1.40) m/s respectively, and those in non-main-side were (2.01±0.94) m/s, (2.40±0.34) m/s, (1.99±1.0) m/s, (2.01±0.65) m/s respectively, which differences between the both sides were of statistical significance (allP<0.05); airflow of middle meatus, inferior meatus and olfactory cleft in the main-side were (2.08±0.43) m/s, (1.60±0.95) m/s, (1.64±0.80)m/s respectively, and those in non-main-side were (1.89±0.52) m/s, (1.49±0.89) m/s, (1.50±0.75) m/s respectively, which differences were significant statistically (allP>0.05); 3. The airflow form appeared to be linear in the middle and inferior parts of the nasal cavity. 4. Velocity in maxillary sinus cavity was almost 0 m/s.CONCLUSIONThe airflow passes mainly through the middle and inferior parts of the meatus with higher velocity in laminar form and airflow of middle meatus, inferior meatus and olfactory cleft are low and the velocity were slow. Besides, airflow in maxillary sinus cavity diffuses free mainly.

Objectives To compare the efficacy and adverse effects of combining all-trans retinoic acid and arsenic triox-ide with or without anthracyclines on the treatment of childhood acute promyelocytic leukemia (APL) patients. Methods The retrospective study included 46 children as newly diagnosed APL from January 1st, 2001 to December 31st , 2012. Efficacy and adverse effects for different induction therapies and in high and low white blood cell (WBC) count subgroups were studied. Results In the non antharcycline containing group, 2 patients died during remission induction, and in the antharcycline containing group none of the patients died. No statistical difference was observed between the antharcycline containing group and the non antharcycline containing group in complete remission, the length of time to achieve molecular complete remission and minimal residual disease quantitative analysis at the end of the induction. The mean duration of high WBC count subgroup in the anthar-cycline containing group was shortened than that of the non antharcycline containing group (P<0.05). The recovery time of the abnormal coagulation was found similar between these two groups. Conclusions The use of antharcycline in induction therapy could shorten the duration of high WBC count and reduced the WBC count peak , thus reduces the risk of early death.

Objectives To investigate the inlfuence of polymorphisms of SLC19A1 80G>A, MDR1 exon26C>T and MDR1 exon21G>T/A on curative effect and adverse reaction of high-dose methotrexate in patients with acute lymphoblastic leukemia. Methods MALDI-TOF-MS technique was used to detect the polymorphisms of SLC19A1 80G>A, MDR1 exon 26C>T and MDR1 exon21G>T/A in 108 patients with acute lymphoblastic leukemia (ALL). The relationship of genetic polymorphism, survival rate and toxicity was analyzed. Results The 36-month event-free survival was not related to any polymorphisms of MDR1 and SLC19A1. Patients with mutant types of MDR1 exon26C>T and MDR1 exon21G>T/A showed a much higher MTX plasma levels at 24 hours and higher incidence of hepatic injury (P<0.05). Conclusions The genetic polymorphism of MDR1 exon26>T, MDR1 exon21G>T/A has a large inlfuence on hepatic toxicity and plasma concentra-tions of MTX.