Objective:To investigate the electrophysiological characteristics of medium spiny neurons(MSNs)expressing D1 or D2 dopamine receptors in the striatum of mice,providing a theoretical basis for exploring their roles in motor disorders,reward,and anxiety-depression.Methods:Six male adult D1-tdTomato and D2-tdTomato mice were used.After anesthesia and decapitation,the brains were quickly removed,and coronal slices were prepared.Whole-cell patch recording were employed to record spontaneous firing,resting membrane potential,and action potential parameters of D1 and D2 MSNs in the striatum.Comparative analyses were conducted to identify differences between the two types of neurons.Results:The frequency of spontaneous excitatory postsynaptic currents(sEPSCs)in D1-MSNs was signifi-cantly lower than that in D2-MSNs(P＜0.001),but there was no difference in amplitude;whereas no significant differences were observed in the frequency or amplitude of spontaneous inhibitory postsynaptic currents(sIPSCs)between D1-MSNs and D2-MSNs.Compared with D1-MSNs,D2-MSNs had a lower resting membrane potential(P＜0.01),a significantly lower rheobase for action potential generation(P＜0.01),and the frequency of action potentials induced by depolarizing current injection was significantly higher in D2-MSNs(P＜0.001).Following perfusion with dopamine(60 μmol/L),the frequency of action potentials in D1-MSNs significantly increased(P＜0.001),while the frequency of action potentials in D2-MSNs significantly decreased(P＜0.001).Conclusion:There are significant differences in the electrophysiological properties between D1-MSNs and D2-MSNs in the striatum of mice.

Objective:To investigate the electrophysiological characteristics of medium spiny neurons(MSNs)expressing D1 or D2 dopamine receptors in the striatum of mice,providing a theoretical basis for exploring their roles in motor disorders,reward,and anxiety-depression.Methods:Six male adult D1-tdTomato and D2-tdTomato mice were used.After anesthesia and decapitation,the brains were quickly removed,and coronal slices were prepared.Whole-cell patch recording were employed to record spontaneous firing,resting membrane potential,and action potential parameters of D1 and D2 MSNs in the striatum.Comparative analyses were conducted to identify differences between the two types of neurons.Results:The frequency of spontaneous excitatory postsynaptic currents(sEPSCs)in D1-MSNs was signifi-cantly lower than that in D2-MSNs(P＜0.001),but there was no difference in amplitude;whereas no significant differences were observed in the frequency or amplitude of spontaneous inhibitory postsynaptic currents(sIPSCs)between D1-MSNs and D2-MSNs.Compared with D1-MSNs,D2-MSNs had a lower resting membrane potential(P＜0.01),a significantly lower rheobase for action potential generation(P＜0.01),and the frequency of action potentials induced by depolarizing current injection was significantly higher in D2-MSNs(P＜0.001).Following perfusion with dopamine(60 μmol/L),the frequency of action potentials in D1-MSNs significantly increased(P＜0.001),while the frequency of action potentials in D2-MSNs significantly decreased(P＜0.001).Conclusion:There are significant differences in the electrophysiological properties between D1-MSNs and D2-MSNs in the striatum of mice.

Objective:To investigate the efficacy and safety of daratumumab (Dara) - combination regimens for newly diagnosed multiple myeloma (NDMM).Methods:A retrospective case series study was conducted. The clinical data of 34 patients with NDMM receiving treatment regimen including Dara from Qilu Hospital of Shandong University, Yantai Yuhuangding Hospital, Huangdao Branch of Affiliated Hospital of Qingdao University and Taian City Central Hospital between April 2020 and March 2022 were retrospectively collected. The efficacy, survival and adverse reactions of patients were analyzed. Cox proportional risk model was used to analyze the factors affecting overall survival (OS) and minimal residual disease (MRD) turning negative.Results:Among 34 patients with NDMM, there were 19 males and 15 females, with 21 cases aged < 65 years and 13 cases aged ≥65 years. The median follow-up duration [ M ( Q1, Q3)] was 22 months (19 months, 26 months), the median of Dara treatment cycles was 7 (5, 11), and the overall response rate (ORR) reached 97.1% (33/34). There were statistically significant differences in the optimal efficacy of patients stratified by receiving hematopoietic stem cell transplantation or not and receiving different treatment cycles (all P ≤ 0.05), while there were no statistically significant differences in patients stratified by other clinical features (all P > 0.05). The 1-year progression-free survival rate was 79.4% and the 1-year OS rate was 94.1%. Multivariate Cox regression analysis showed that the cycle number of treatment regimens containing Dara was an independent influencing factor of MRD turning negative (6 cycles vs. 2 cycles, HR = 0.267, 95% CI: 0.076-0.935, P = 0.039); age ≥ 65 years was an independent risk factor for OS ( HR = 35.313, 95% CI: 1.709-729.669, P = 0.021). The incidence of hematological adverse reactions grade 3 or above was 20.6% (7/34), and the non-hematological adverse reactions primarily included infection [44.1% (15/34)] and edema of extremity and trunk [41.2% (14/34)]. Conclusions:The Dara-based regimens for NDMM exhibit a high ORR. The remission depth accelerated with the increasing number of treatment cycle, and the adverse reactions are mild.

Objective:To investigate the clinical features of IgD multiple myeloma (MM) and the effect and prognosis of daratumumab-based combination therapy.Methods:The clinicopathological data of a IgD MM patient with disease progression and extramedullary infiltration treated with daratumumab in the Affiliated Hospital of Qingdao University in December 2019 were retrospectively analyzed.Results:The 74-year-old woman was diagnosed as IgD MM by bone marrow aspiration and immunofixation electrophoresis. The patient was given VD (bortezomib, dexamethasone), RD (lenalidomide, dexamethasone) and ID (ixazomib, dexamethasone) regimens. In June 2020, the patient developed multiple subcutaneous nodules, and she was assessed as progressive disease with extensive extramedullary infiltration. After treated with daratumumab-PAD (liposomal doxorubicin, bortezomib, dexamethasone) regimen, the patient's subcutaneous nodules were significantly reduced and partially disappeared, and the general condition was significantly improved. But the patient was in a cachexia state and finally died of the irregular treatment and disease progression.Conclusions:IgD MM has a low incidence and a short survival period, and there is no uniform standard treatment. The early application of daratumumab combined with proteasome inhibitors, immunomodulators, cytotoxic drugs and hematopoietic stem cell transplantation may improve the overall survival of patients.

Objective:By analyzing the clinical and pathologic manifestations of systemic mastocytosis (SM) to improve the recognition of the disease.Methods:Clinical manifestations, diagnosis and treatment of a middle-aged male patient with SM was reported with multidisciplinary discussions.Results:A middle-aged man with bone pain, thyroid nodules and lymphadenectasis came to our clinic. Thyroid cancer with lymph node and bone metastasis was suspected by imaging examination. The pathological results showed cell proliferation with transparent cytoplasm and irregular nuclear in the trabecular bone. Toluidine blue staining showed the proliferated cells were mast cells(+). Immunohistochemistry showed proliferating mast cells stained with CD117 and CD2. SM with extensive bone marrow involvement was diagnosed and treated with thalidomide and calcitriol.Conclusion:Knowing the characteristics of SM is helpful for accurate diagnosis and treatment.

Objective: To investigate the effect of immunophenotyping on prognosis of multiple myeloma (MM) patients treated with bortezomib regimen as main treatment. Methods: Seventy-six MM patients in the Department of Hematology in the Affiliated Hospital of Qingdao University from January 2012 to January 2017 were retrospectively analyzed. The effects of the expressions of CD45, CD56 and other factors on progression free survival (PFS) and overall survival (OS) in MM patients treated with bortezomib-containing regimen were also analyzed. Results: Univariate analysis showed that statistical differences of the median PFS (12 months vs. 19 months, P < 0.001) and median OS (19 months vs. 23 months, P= 0.001) were significant in the group of CD45 positive and negative of MM patients; the median PFS (14 months vs. 21 months, P= 0.014) and median OS (16 months vs. 25 months, P= 0.026) for MM patients with hemoglobin (Hb) < 100 g/L and Hb ≥ 100 g/L were statistically significant; the median PFS (13 months vs. 18 months, P= 0.004) and median OS (14 months vs. 24 months, P= 0.008) for MM patients with albumin (ALB) < 35 g/L and ALB ≥ 35 g/L were statistically significant. The median PFS time and the median OS time in female MM patients were shorter than those in male MM patients (13 months vs. 19 months, P= 0.008; 16 months vs. 25 months, P= 0.008). Multivariate analysis showed that female and CD45 positive were the independent poor prognostic factors for PFS and OS in MM patients (P < 0.05). Conclusion CD45 positive and female are important prognostic factors for MM patients treated with bortezomib regimen as main treatment.

Objective By analyzing the clinical manifestations and pathologic features of Erdheim-Chester's disease (ECD) to improve the recognition of the disease.Methods The clinical characteristics,diagnosis and treatment of a young male with ECD were reported and the related literature was reviewed.Results A previously healthy young male patient with bilateral exophthalmos,blurred vision of right eye,polyuria and hypertension without obvious causes for nine months were admitted into our hospital.He developed low back pain two months ago.Thoracic vertebra Magnetic resonance imaging (MRI) showed multiple nodules extending from the 2th-7th thoracic vertebrae intra-medullary.MRI of the brain showed multiple masseswith abnormal intensities within the retro-ocular intraconal muscle cone,sellar and cavernous sinus,maxillary sinus.Biopsy specimens from the right orbital lesion demonstrated proliferation of fibrous connective tissue and fat tissue infiltrating with lymphocytes,plasma cells,eosinophils,foam cells,spindle cells,and multinucleated giant cells accompanied by fat necrosis.Immunohistochemistry showed infiltrated lymphocytes stained positive for CD68,CD20,CD3,LCA and negative for CD1a,S-100 protein and langerin.The clinical symptoms of exophthalmos and low back pain relieved after treated with methylprednisolone and interferon-α.Conclusion Understanding the characteristics of ECD can help to make the correct diagnosis and treatment.

Philadelphia chromosome-positive acute myeloid leukemia is controversial and difficult to distinguish from the blast phase of chronic myeloid leukemia.As a myeloid neoplasm,rare cases of this leukemia manifest multiple soft-tissue tumors or bone lytic lesions.In this paper,we describe a 49-year-old male patient who had an abrupt onset with sharp chest pain,fever,fatigue,emaciation,and splenomegaly.18F-fluoro-deoxy-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) result showed diffuse and uneven hypermetabolic lesions in the bone marrow with peripheral bone marrow expansion,multiple soft tissue neoplasms with high 18F-FDG uptake,and lytic bone lesions.Bone marrow smear and biopsy detected aberrant blast cells expressing myeloid rather than lymphoid immunophenotype marker.For the existence of Philadelphia chromosome and BCR-ABL1 fusion gene together with complex chromosome abnormalities,a diagnosis of Philadelphia-positive acute myeloid leukemia was made,although the type (de novo or blast crisis) remained unclear.

Objective:To evaluate the promoting surgery incision healing effect of recombinant human acidic fibroblast growth fac-tor ( rh-aFGF) in the treatment of children with open fractures. Methods:A multicenter, randomized and controlled clinical trial was conducted to study the efficacy of rh-aFGF. Totally 120 cases of injured children (age<14y) were randomly divided into two groups, the treatment group (n=60) was given rh-aFGF washing during the operation and spraying after the operation, and the control group ( n=60) was treated with normal saline. Both groups were given traction, screw or Kirschner wire fixation. The healing time, healing status and delayed healing were observed and compared in the two groups. Results:Stage I healing rate, the complete healing time and delayed healing rate in the treatment group was 86. 6%, (20. 3 ± 5. 6)d and 3. 3%, respectively, while that in the control group was 56.7%, (23.4 ±6.2)d and 15.0%, respectively. The differences between the two groups were significant (P<0.05 or 0.01). Conclusion:Rh-aFGF can effectively promote wound healing and shorten the healing time. For all these positive aspects,rh-aFGF de-serves wider clinical application in postoperative rehabilitation after open fractures.

Objective To find direct effect of Chinese herbs Bu Gu Zhi (Psoralea corylifolia L) and Bai Zhi (Dahurian angelica root) Extracts on melanocyte adhesion and migration in vitro. Methods Ethanol extracts obtained from two kind of Chinese medicinable herbs were tested. Human melanocytes were obtained from neonatal foreskins and 48-well culture dish covered with fibronectin were used to perform melanocyte adhesion assay; Motility was assessed using the micropore filter method. Results: The extracts of Bu Gu Zhi(Psoralea corylifolia L), Bai Zhi(Dahurian angelica root) obviously showed an effect in increasing of human melanocyte adhesion and migration on fibronectin. Conclusion It is suggested that Buguzhi(Fructus Psoraleae) and Baizhi(Radix Angelicae Dahuricae) might induce melanocyte adhesion and/or migration in the treatment of vitiligo.