Objectives:This study aimed to assess the efficacy and safety of bendamustine in combination with rituximab (BR regimen) for the treatment of newly diagnosed indolent B-cell non-Hodgkin's lymphoma (B-iNHL) and elderly mantle cell lymphoma (eMCL) .Methods:From December 1, 2020 to September 10, 2022, a multi-center prospective study was conducted across ten Grade A tertiary hospitals in Shandong Province, China. The BR regimen was administered to evaluate its efficacy and safety in newly diagnosed B-iNHL and eMCL patients, and all completed at least four cycles of induction therapy.Results:The 72 enrolled patients with B-iNHL or MCL were aged 24-74 years, with a median age of 55 years. Eastern Cooperative Oncology Group (ECOG) performance status scores of 0-1 were observed in 76.4% of patients, while 23.6% had scores of 2. Disease distribution included follicular lymphoma (FL) (51.4% ), marginal zone lymphoma (MZL) (33.3% ), eMCL (11.1% ), and the unknown subtype (4.2% ). According to the Ann Arbor staging system, 16.7% and 65.3% of patients were diagnosed with stage Ⅲ and stage Ⅳ lymphomas, respectively. Following four cycles of BR induction therapy, the overall response rate was 98.6%, with a complete response (CR) rate of 83.3% and a partial response (PR) rate of 15.3%. Only one eMCL patient experienced disease progression during treatment, and only one FL patient experienced a relapse. Even when evaluated using CT alone, the CR rate was 63.9%, considering the differences between PET/CT and CT assessments. The median follow-up duration was 11 months (range: 4-22), with a PFS rate of 96.8% and an OS rate of 100.0%. The main hematologic adverse reactions included grade 3-4 leukopenia (27.8%, with febrile neutropenia observed in 8.3% of patients), grade 3-4 lymphopenia (23.6% ), grade 3-4 anemia (5.6% ), and grade 3-4 thrombocytopenia (4.2% ). The main non-hematologic adverse reactions such as fatigue, nausea/vomiting, rash, and infections occurred in less than 20.0% of patients.Conclusion:Within the scope of this clinical trial conducted in China, the BR regimen demonstrated efficacy and safety in treating newly diagnosed B-iNHL and eMCL patients.

Objective:To construct a cognitive training program suitable for elderly patients with mild cognitive impairment based on horticultural therapy, so as to effectively slow down the cognitive decline of patients with mild cognitive impairment.Methods:Through searching the Chinese and English database literature of cognitive intervention from July 2000 to July 2020 and field visits to nursing homes, the draft intervention plan was formed. Two rounds of focus group interview were held to consult experts in cognitive impairment and geriatric care, etc., and to revise the intervention plan.Results:In the two rounds of focus group interview, the expert positive coefficient was 100%, the expert judgment basis was 0.84, the expert familiarity degree was 0.84, and the expert authority coefficient was 0.84. In the end, a 10-week cognitive intervention program targeting six cognitive domains -- "visuospatial/executive ability", "memory ability", "language ability", "attention ability", "abstract ability" and "naming ability" was formed, and the implementation steps of the program were improved.Conclusions:The construction process of cognitive training program for patients with mild cognitive impairment based on horticultural therapy theory is rigorous, scientific and feasible, and can be used to guide the cognitive training of patients with mild cognitive impairment.

Objective:To observe the effect of hyperbilirubinemia on glomerulus of rats, and to explore its dose-response and mechanism.Methods:Twenty-four adult male Sprague-Dawley (SD) rats were divided into four groups according to the random number table method, with 6 rats in each group. Hyperbilirubinemia rat model was reproduced by intraperitoneal injection of bilirubin once every 12 hours for 4 times, at doses of 50, 100, and 200 mg/kg in low, medium, and high dose bilirubin group (LB group, MB group, HB group), respectively. The rats in negative control group (NC group) were given the same solvent without bilirubin powder. Urine was collected 24 hours after administration, and total protein (TP) level was detected. Then the rats were sacrificed, the blood was collected by cardiac puncture, and the total bilirubin (TBil) and direct bilirubin (DBil) levels were measured by automatic biochemical analyzer. The renal tissue was collected and stained with periodic acid-Schiff (PAS) staine, the glomerular morphology was observed under light microscope, and the glomerular injury score was performed. Podocyte morphology was observed by transmission electron microscopy after uranium acetate and lead citrate double staining. The activity of superoxide dismutase (SOD) and content of malondialdehyde (MDA) were determined by colorimetric method. The expression level of podocyte specific marker Wilms tumor protein-1 (WT-1) was determined by Western blotting.Results:With the increase of bilirubin dose, the contents of 24-hour urine TP, blood TBil, blood DBil and MDA content in kidney tissue were gradually increased, and the SOD activity and WT-1 expression in kidney tissue were gradually decreased. The differences between LB group, MB group, HB group and NC group were statistically significant [24-hour urine TP (mg): 24.85±2.22, 52.57±3.66, 56.84±3.49 vs. 7.50±1.33; blood TBil (μmol/L): 37.75±2.19, 81.37±2.13, 125.13±9.96 vs. 5.53±0.41; blood DBil (μmol/L): 15.50±1.96, 37.88±1.05, 64.53±2.89 vs. 2.38±0.35; kidney MDA (μmol/g): 3.14±0.65, 5.01±0.28, 7.50±1.08 vs. 2.30±0.20; kidney SOD (kU/g): 95.91±10.43, 57.06±15.90, 37.12±11.72 vs. 113.91±12.16; kidney WT-1 protein (WT-1/GAPDH): 0.280±0.006, 0.239±0.006, 0.198±0.001 vs. 0.361±0.005; all P < 0.05]. It was shown under light microscope that uneven thickness of mesangial membrane and basement membrane of the glomerulus, and some of them were accompanied by hyperplasia and widening. The glomerular injury score increased with the increase in bilirubin dose. The differences between LB group, MB group, HB group and NC group were statistically significant (17.50±1.05, 25.00±1.41, 34.00±1.41 vs. 11.67±0.82, all P < 0.05). Transmission electron microscopy showed that with the increase of bilirubin dose, the damage of glomerular podocytes was aggravated. Conclusions:Hyperbilirubinemia induced damage to glomerulus in a dose-dependent manner. In the lethal dose range, the higher the dose, the stronger the damage, which might be related to the oxidative stress promoted by bilirubin and the damage of glomerular podocytes.

Objective:To explore the application of computer simulation teaching based on GasMan @ software in anesthesiology standardized nursing training. Methods:Thirty-six anesthesia nurses undergoing standardized training were selected as research objects. They were randomly divided into the traditional teaching group (group C) and the computer simulation teaching based on GasMan @ software group (group G), with 18 nurses in each group. All the nurses received the theory test before and after the training, and the practical operation assessment and the teaching satisfaction survey were conducted after the training. SPSS 17.0 was used for independent-samples t test and chi-square test. Results:There was no significant difference in the theoretical test scores of the anesthesia nurses before class between the two groups ( P > 0.05); the theoretical test, practical performance and satisfaction survey of group G were significantly better than those of group C, with statistical significance ( P < 0.05). Conclusion:Computer simulation teaching based on GasMan @ software is in favor of the anesthesia nurse to learn and master the relevant theory of inhalation general anesthesia, especially to improve practical skills.

Objective:To evaluate the optimized effect of infiltration between the popliteal artery and the capsule of the knee (IPACK)-adductor canal block (ACB) combined with general anesthesia when used for the total knee arthroplasty.Methods:Sixty patients of both sexes, aged 18-64 yr, with body mass index of 18-24 kg/m 2, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, scheduled for elective unilateral total knee arthroplasty, were divided into 2 groups ( n=30 each) using a random number table method: IPACK-ACB combined with general anesthesia group (group IA) and conventional anesthesia femoral nerve block-popliteal superior sciatic nerve block combined with general anesthesia group (group C). Before induction of general anaesthesia, 0.375% ropivacaine 15 ml was injected for IPACK and 0.375% ropivacaine 25 ml for ACB under the ultrasound guidance in group IA, femoral nerve block and popliteal superior sciatic nerve block was performed under the guidance of ultrasound combined with a nerve stimulator and 0.375% ropivacaine 20 ml was injected in group C. After confirming the efficacy of nerve block, total intravenous anesthesia was carried out to maintain bispectral index values at 40-60.Patient-controlled intravenous analgesia was performed with sufentanil after operation, and the visual analog scale score was maintained ≤ 3.The quadriceps muscle strength score was recorded when discharge from postanesthesia care unit and at 24, 48 and 72 h after surgery.The first postoperative off-bed time and development of foot drop in awake patients after surgery, requirement for rescue analgesia and adverse reactions were recorded.The postoperative length of hospital stay and score for patients′ satisfaction with postoperative recovery were also recorded. Results:Compared with group C, the postoperative quadriceps muscle strength scores and score for patients′ satisfaction with postoperative recovery were significantly increased, the incidence of postoperative foot drop was decreased, and the length of hospital stay and first postoperative off-bed time were shortened in group IA ( P<0.05). Conclusion:IPACK-ACB combined with general anesthesia may be an optimized strategy which is helpful for outcomes after total knee arthroplasty.

Objective: To evaluate the effect of ATP-binding cassette B subfamily member 1 transporter (ABCB1) C3435T genetic polymorphism on the efficacy of postoperative analgesia. Methods: One hundred American Society of Anesthesiologists physical status Ⅱ or Ⅲ patients, aged 18-60 yr, scheduled for elective thoracoscopic lobectomy under general anesthesia, were enrolled in this study.The gene mutation of ABCB1 C3435T was detected, and the patients were divided into 3 groups according to the genotypes: wild homozygote group (CC group), mutation heterozygote (CT group) and mutation homozygote group (TT group). Patient-controlled intravenous analgesia was performed with sufentanil after operation.Visual analogue scale (VAS) scores at 24 and 48 h after operation, postoperative consumption of sufentanil, sleep quality score at 24 h after operation and state-trait anxiety score were recorded. Results: Compared with CC group, VAS scores at 24 h after operation and postoperative consumption of sufentanil were significantly decreased in TT and CT groups, and the state-trait anxiety score was significantly decreased in TT group and increased in CT group (P<0.05). Compared with TT group, VAS scores at 24 h after operation, postoperative consumption of sufentanil and the state-trait anxiety score were significantly increased in CT group (P<0.05). There was no significant difference in sleep quality scores among the three groups (P>0.05). Conclusion ABCB1 C3435T genetic polymorphism may be one of the mechanisms of the individual variation in the efficacy of postoperative analgesia.

Objective To study the differentiation types of microglia induced by macrophage colony-stimulating factor (M-CSF).Methods Rat microglia cultured in vitro were inoculated on 6-well plates and divided into 3 groups (n=4 each) using a random number table method when cell confluence reached 70％:blank control group (C group),vehicle control group (P group) and M-CSF group.Group P was incubated with phosphate buffer solution for 7 days and group M-CSF with 20 ng/ml M-CSF for 7 days.The expression of a specific M1 phenotype marker tumor necrosis factor-alpha (TNF-α) and specific M2 phenotype markers interleukin-10 (IL-10) and brain-derived neurotrophic factor (BDNF) was determined by Western blot.Results Compared with C group,the expression of IL-10 and BDNF was significantly upregulated (P＜0.05),and no significant change was found in TNF-α expression in M group (P＞0.05),and no significant change was found in the expression of TNF-α,IL-10 or BDNF in P group (P＞0.05).Conclusion M-CSF can induce microglia to differentiate into a M2 phenotype.

Objective To evaluate the effect of tripterine on hydrochloric acid-induced acute lung injury(ALI)in mice.Methods Eighteen pathogen-free healthy adult male ICR mice,aged 7-9 weeks,weighing 25-30 g,were divided into 3 groups(n=6 each)using a random number table:control group(group C),hydrochloric acid-induced ALI group(group ALI)and tripterine group(group T).ALI was induced by a single intratracheal instillation of hydrochloric acid 2 ml/kg(pH 1.5)via a 24-gauge angiocatheter inserted into the trachea in pentobarbital sodium-anesthetized mice.Tripterine 3 mg/kg was injected intraperitoneally once a day for 3 consecutive days,and then the model was established in group T.The mice were sacrificed at 6 h after instillation,and lung specimens were obtained for microscopic examination and for determination of the levels of tumor necrosis factor-alpha(TNF-α),interleukin-6(IL-6),macrophage migration inhibitory factor(MIF)and myeloperoxidase(MPO)in lung tissues.Results Compared with group C,the levels of TNF-α,IL-6,MIF and MPO were significantly increased at 6 h after instillation in ALI and T groups(P<0.01).Compared with group ALI,the levels of TNF-α,IL-6,MIF and MPO were significantly decreased at 6 h after instillation in group T(P<0.01).The pathological changes of lung tissues were significantly attenuated in group T compared with group ALI.Conclusion Tripterine can attenuate hydrochloric acid-induced ALI in mice.

Objective To evaluate the role of c?Jun N?terminal kinase ( JNK) and p38 mitogen?ac?tivated protein kinase ( p38MAPK) signaling pathways in attenuation of myocardial ischemia?reperfusion ( I∕R) injury by morphine postconditioning. Methods Healthy adult male Sprague?Dawley rats, weighing 180-240 g, were used in the study. Their hearts were excised and retrogradely perfused in a Langendorff apparatus with Krebs?Ringer ( K?R) buffer saturated with 95% O2?5% O2 at 37℃. After 15 min of equili?bration, 52 isolated hearts were divided into 4 groups ( n=13 each) using a random number table: control group (group C), I∕R group, morphine postconditioning group (group MP), and morphine postcondition?ing plus anisomycin group ( group MP+A) . The hearts were continuously perfused with K?R buffer for 105 min in group C. In group I∕R, the hearts were subjected to 45 min of global ischemia by stopping perfusion with K?R buffer, followed by 60 min of reperfusion by restoration of perfusion with K?R buffer. In group MP, the hearts were subjected to 45 min of global ischemia, followed by 10 min of reperfusion with K?R buffer containing 3?0 μmol∕L morphine and then by 50 min of reperfusion with K?R buffer. In group MP+A, the hearts were subjected to 45 min of global ischemia, followed by 10 min of reperfusion with K?R buffer containing 3?0 μmol∕L morphine and 1?0 μmol∕L anisomycin ( an activator of JNK and p38MAPK) and then by 50 min of reperfusion with K?R buffer. At 60 min of reperfusion, 8 hearts in each group were selected for measurement of the myocardial infarction and amount of creatine kinase?MB ( CK?MB) released from the myocardium, and the myocardial infarct size was calculated. At 20 min of reperfusion, 5 hearts in each group were selected to detect the expression of phosphorylated JNK ( p?JNK ) , phosphorylated p38MAPK ( p?p38MAPK) and cytochrome c ( Cyt c) in myocardial tissues ( by Western blot) and content of nicotinamide adenine dinucleotide ( NAD+) in myocardial tissues ( by spectrophotometry ) . Results Compared to group C, the myocardial infarct size and amount of CK?MB released from the myocardium were significantly increased, the expression of p?JNK, p?p38MAPK and Cyt c was significantly up?regulated, and the content of NAD+ was significantly decreased in I∕R, MP and MP+A groups ( P<0?05) . Compared to group I∕R, the myocardial infarct size and amount of CK?MB released from the myocardium were signifi?cantly decreased in MP and MP+A groups, and the expression of p?JNK, p?p38MAPK and Cyt c was sig?nificantly down?regulated, and the content of NAD+ was significantly increased in group MP (P<0?05). Compared to group MP , the myocardial infarct size and amount of CK?MB released from the myocardium were significantly increased, the expression of p?JNK, p?p38MAPK and Cyt c was significantly up?regula?ted, and the content of NAD+ was significantly decreased in group MP+A (P<0?05). Conclusion The mechanism by which morphine postconditioning attenuates myocardial I∕R injury is related to inhibition of activation of JNK and p38MAPK signaling pathways in rats.

Objective To evaluate the effect of dexmedetomidine on acute kidney injury after cardiac valve replacement with cardiopulmonary bypass (CPB).Methods One hundred patients of both sexes with rheumatic heart disease,aged 32-64 yr,weighing 46-75 kg,of American Society of Anesthesiologists physical status Ⅱ or Ⅲ (New York Heart Association class Ⅱ or Ⅲ),scheduled for elective cardiac valve replacement with CPB,were divided into 2 groups (n =50 each) using a random number table:control group (group C) and dexmedetomidine group (group D).Dexmedetomidine was intravenously infused in a loading dose of 1 μg/kg over 10 min before induction of anesthesia followed by an infusion of 0.4 μg · kg-1 · h-1 until 24 h after operation in group D,while the equal volume of normal saline was given in group C.The urine output per hour during the postoperative 48 h period was recorded.At 6,12,24,36 and 48 h after operation,blood samples were collected from the median cubital vein for determination of serum creatinine levels.The development and severity of acute kidney injury were determined according to the urine output and serum creatinine level.Results Compared with group C,the incidence and severity of acute kidney injury were significantly decreased in the postoperative 48 h period in group D (P＜0.05).Conclusion Dexmedetomidine infused in a loading dose of 1 μg/kg over 10 min before induction of anesthesia followed by an infusion of 0.4 μg · kg-1 · h-1 until 24 h after operation can reduce the development and severity of acute kidney injury after cardiac valve replacement with CPB in patients.