Objective: To evaluate the efficacy and safety of bendamustine combined with pomalidomide and dexamethasone (BPD regimen) in the treatment of relapsed multiple myeloma (MM) with extramedullary disease. Methods: This open, single-arm, multicenter prospective cohort study included 30 relapsed MM patients with extramedullary disease diagnosed in seven hospitals including Qingdao Municipal Hospital. The patients were treated with BPD regimen from February 2021 to November 2022. This study analyzed the efficacy and adverse reactions of the BPD regimen. Results: The median age of the 30 patients was 62 (47-72) years, of which 18 (60% ) had first-time recurrence. The overall response rate (ORR) of the 18 patients with first-time recurrence was 100%, of which three (16.7% ) achieved complete remission, 10 (55.5% ) achieved very good partial remission (VGPR), and five (27.8% ) achieved partial remission (PR). The ORR of 12 patients with recurrence after second-line or above treatment was 50%, including zero patients with ≥VGPR and six patients (50% ) with PR. Three cases (25% ) had stable disease, and three cases (25% ) had disease progression. The one-year progression free survival rate of all patients was 65.2% (95% CI 37.2% -83.1% ), and the 1-year overall survival rate was 90.0% (95% CI 76.2% -95.4% ). The common grade 3-4 hematology adverse reactions included two cases (6.7% ) of neutropenia and one case (3.3% ) of thrombocytopenia. The overall adverse reactions are controllable. Conclusions: The BPD regimen has good efficacy and tolerance in relapsed MM patients with extramedullary disease.
Humans ; Middle Aged ; Aged ; Multiple Myeloma/drug therapy* ; Bendamustine Hydrochloride/therapeutic use* ; Prospective Studies ; Dexamethasone/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

[Abstract] Objective To investigate the effect and possible mechanism of cell cycle-dependent kinase (Cdk)5 inhibitor Roscovitine on 1-methyl4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced pathological changes in brain regions associated with Parkinson’ s disease (PD) model mice. Methods The effect of Roscovitine on the relative expression levels of P25 and Cdk5 proteins was detected by Western blotting in MPP

OBJECTIVE: To observe the effects of moxibustion on the stem cell factor (SCF)/tyrosine kinase receptor (c-kit) signaling pathway and immune function in rats with diarrhea irritable bowel syndrome (IBS-D), and to explore the mechanism of moxibustion for IBS-D. METHODS: Among 52 young rats born from 6 healthy pregnant SPF rats, 12 rats were randomly selected into the normal group, and the remaining 40 rats were treated with the three-factor combination method of maternal separation, acetic acid enema and chronic restraint stress to establish the IBS-D rat model. Thirty-six rats with successful IBS-D model were randomly divided into a model group, a moxibustion group, and a medication group, 12 rats in each group. The rats in the moxibustion group were treated with suspension moxibustion at "Tianshu" (ST 25) and "Shangjuxu" (ST 37); the rats in the medication group were treated with intragastric administration of rifaximin suspension (150 mg/kg). All the treatments were given once a day for 7 consecutive days. The body mass, loose stool rate (LSR), the minimum volume threshold when abdominal withdrawal reflex (AWR) scored 3 were measured before acetic acid enema (35 days old), after modeling (45 days old), and after intervention (53 days old). After intervention (53 days old), HE staining was used to observe the morphology of colon tissue, and spleen and thymus coefficients were measured; ELISA method was used to detect serum inflammatory factors (tumor necrosis factor a [TNF-a], interleukin [IL]-10, IL-8), T-lymphocyte subsets (CD⁺₄, CD⁺₈, CD⁺₄₅), value of CD⁺₄/CD⁺₈ and immune globulin (IgA, IgG, IgM); real-time PCR method and Western blot method was used to detect the expression of SCF, c-kit mRNA and protein in colon tissue; immunofluorescence staining method were used to detect positive expression of SCF and c-kit. RESULTS: After intervention, compared with the normal group, in the model group, the body mass and the minimum volume threshold when AWR scored 3 were decreased (P<0.01), LSR, spleen and thymus coefficients, serum levels of TNF-α, IL-8, CD⁺₄, CD⁺₄₅, CD⁺₄/CD⁺₈, IgA, IgG, IgM were increased (P<0.01), serum IL-10 level and protein and mRNA expression of SCF and c-kit in colon tissue were decreased (P<0.01), and the positive expression of SCF and c-kit was decreased (P<0.01). Compared with the model group, in the moxibustion group and the medication group, the body mass and the minimum volume threshold when AWR scored 3 were increased (P<0.01, P<0.05), LSR, spleen and thymus coefficients, serum levels of TNF-α, IL-8, CD⁺₄, CD⁺₈, CD⁺₄₅, CD⁺₄/CD⁺₈, IgA, IgG, IgM were decreased (P<0.01, P<0.05), serum IL-10 level and protein and mRNA expression of SCF and c-kit in colon tissue were increased (P<0.01), and the positive expression of SCF and c-kit was increased (P<0.01). Compared with the medication group, in the moxibustion group, the level of serum CD⁺₄ was decreased (P<0.05), the value of CD⁺₄/CD⁺₈ was increased (P<0.01), and there was no significant difference in other indexes (P>0.05). The expression of SCF and c-kit mRNA was positively correlated with the minimum volume threshold when AWR scored 3 and IL-10 (P<0.01), and negatively correlated with remaining indexes (P<0.01, P<0.05). CONCLUSION Moxibustion could reduce visceral hypersensitivity, improve symptoms of abdominal pain and diarrhea in IBS-D rats, and its mechanism may be related to up-regulation of the expression of SCF/c-kit signaling pathway and improvement of IBS-D immune function.
Rats ; Animals ; Irritable Bowel Syndrome/therapy* ; Moxibustion/methods* ; Rats, Sprague-Dawley ; Interleukin-10 ; Interleukin-8 ; Maternal Deprivation ; Tumor Necrosis Factor-alpha ; Diarrhea ; Signal Transduction ; Homeostasis ; Receptor Protein-Tyrosine Kinases ; Immunity ; Immunoglobulin A ; Immunoglobulin M

OBJECTIVE: To observe the effect of moxibustion on the regulation of nuclear factor-kappa B (NF-κB) and inflammatory factors by multiple microRNAs (miRNAs) in rats with diarrhea-predominant irritable bowel syndrome (IBS-D), and to explore the anti-inflammatory mechanism of moxibustion on IBS-D. METHODS: Twelve of 52 newborn rats were randomly selected into a normal group. The remaining rats were made into IBS-D model. A total of 36 rats with successful model were randomly divided into a model group, a medication group and a moxibustion group, 12 rats in each group. The rats in the medication group were intraperitoneally injected with pyrrolidine dithiocarbamate (PDTC). The rats in the moxibustion group were treated with moxibustion at "Tianshu" (ST 25) and "Shangjuxu" (ST 37) for 20 min each time. All the intervention was given once a day for 7 days. Before and after modeling as well as after intervention, the body mass, loose stool rate and the minimum volume threshold of abdominal withdrawal reflex (AWR) were measured. After intervention, the contents of serum tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-8 were detected by ELISA method; the morphology of colon tissues was observed by HE staining, and the expressions of miR-155, miR-125b, miR-29b, miR-31, miR-18a and NF-κB p65 mRNA in colon tissues were detected by real-time PCR. The expressions of NF-κB p65, TNF-α, IL-1β and IL-8 protein in colon tissues were detected by immunofluorescence. RESULTS: After modeling, the body mass and the minimum volume threshold of AWR in the model group were lower than those in the normal group (P<0.01); the rates of loose stool in the model group were higher than those in the normal group (P<0.01); after intervention, in the model group, the inflammatory infiltration of colon tissues was obvious, and the serum levels of TNF-α, IL-1 β, IL-8 were higher than those in the normal group (P<0.05); the expression of miR-155, miR-125b, miR-29b, miR-31, miR-18a and NF-κB p65 mRNA in colon tissues was higher than that in the normal group (P<0.05); the protein expression of NF-κB p65, TNF-α, IL-1β, IL-8 was also higher than that in the normal group (P<0.01). After intervention, the body mass and the minimum volume threshold of AWR in the medication group and the moxibustion group were both higher than those in the model group (P<0.05); the loose stool rate in the medication group and the moxibustion group were lower than those in model group (P<0.05); the inflammatory cells infiltration in the colon tissues was less, the serum levels of TNF-α, IL-1β and IL-8 as well as the protein expression of NF-κB p65, TNF-α, IL-1β and IL-8 in the colon tissues in the medication group and the moxibustion group were lower than those in the model group (P<0.05, P<0.01). The expression of miR-125b, miR-31, miR-18a and NF-κB p65 mRNA in the medication group were lower than those in the model group (P<0.05). The expression of miR-155, miR-125b, miR-29b, miR-31, miR-18a and NF-κB p65 mRNA in the moxibustion group were lower than those in the model group (P<0.05). The miR-155, miR-125b, miR-29b, miR-31, miR-18a were positively correlated with NF-κB p65 mRNA (0<r<1, P<0.01). CONCLUSION The anti-inflammatory mechanism of moxibustion at "Tianshu" (ST 25) and "Shangjuxu" (ST 37) for IBS-D rats may be related to regulating multiple miRNAs to inhibit NF-κB signal pathway and reduce the expression of inflammatory factors.
Animals ; Diarrhea/therapy* ; Interleukin-8/genetics* ; Irritable Bowel Syndrome/therapy* ; MicroRNAs/genetics* ; Moxibustion ; NF-kappa B/metabolism* ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Tumor Necrosis Factor-alpha/genetics*

Professor CHU Hao-ran believes that the clinical diagnosis and treatment of diarrhea-predominant irritable bowel syndrome with acupuncture and moxibustion should concentrate on the integration of disease and syndrome differentiation. According to the evolution of pathogenesis, this disease is divided into 4 stages, i.e. invasion of exogenous pathogens, liver stagnation and spleen deficiency, spleen and kidney yang deficiency and interaction of cold and heat. Hence, the treatment should be provided by stages. Focusing on regulating the spleen and stomach, a specific acupuncture-moxibustion prescription is proposed, including Tianshu (ST 25), Zhongwan (CV 12), Zusanli (ST 36) and Shangjuxu (ST 37). Additionally, the combination of distal and nearby acupoints is considered and an unique needling manipulation, named the fight between dragon and tiger, is exerted. On the base of syndrome and meridian differentiation, the modern medicine is combined, stressing on the mind regulation and the mutual application of acupuncture and moxibustion in treatment. Eventually, a distinctive treatment system with acupuncture and moxibustion is formed for "regulating the spleen and stomach and differentiating meridians".
Acupuncture ; Acupuncture Points ; Acupuncture Therapy ; Diarrhea/therapy* ; Humans ; Irritable Bowel Syndrome/therapy* ; Meridians ; Moxibustion

OBJECTIVE: To observe the regulative effect of Tongdu Tiaoshen acupuncture on the depression-like behavior and cAMP-response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF)/tyrosine protein kinase B (TrkB) signaling pathway of hippocampus in rats with post-stroke depression (PSD), and to explore its possible mechanism on improving PSD. METHODS: A total of 36 SPF SD rats were randomized into a sham operation group, a model group and a Tongdu Tiaoshen group, 12 rats in each group. The compound method of Zea Longa suture-occlusion and chronic unpredictable mild stress (CUMS) was used to establish the PSD model in rats of the model group and the Tongdu Tiaoshen group. On the 4th day after modeling, acupuncture was applied at "Dazhui" (GV 14), "Shuigou" (GV 26), "Baihui" (GV 20) and "Shenting" (GV 24) in the Tongdu Tiaoshen group, 40 min every time, once a day, 6 times a week for 4 weeks consecutively. On the 2nd day after PSD modeling and after 4-week intervention, Zea Longa neurobehavioral score was evaluated, sucrose water consumption test and open-field test were performed; biochemical method was used to detect the SOD, CAT activity and MDA level in hippocampal CA1 area; ELISA method was used to detect the serum level of BDNF; real-time PCR was used to detect the mRNA expression of BDNF, TrkB and CREB in hippocampal CA1 area; Western blot was used to detect the protein expression of BDNF, TrkB, CREB and p-CREB in hippocampal CA1 area. RESULTS: Compared with the sham operation group, Zea Longa neurobehavioral scores were increased (P<0.05), percentage of sucrose water consumption, horizontal motion and vertical motion scores of open-field test were decreased after modeling and intervention in the model group and after modeling in the Tongdu Tiaoshen group (P<0.05). Compared with the model group, Zea Longa neurobehavioral score was decreased (P<0.05), percentage of sucrose water consumption, horizontal motion and vertical motion scores of open-field test were increased after intervention in the Tongdu Tiaoshen group (P<0.05). Compared with the sham operation group, the SOD and CAT activity in hippocampal CA1 area and serum level of BDNF were decreased (P<0.05), MDA level in hippocampal CA1 area was increased in the model group (P<0.05); compared with the model group, the SOD and CAT activity in hippocampal CA1 area and serum level of BDNF were increased (P<0.05), MDA level was decreased in the Tongdu Tiaoshen group (P<0.05). Compared with the sham operation group, the mRNA expression of BDNF, TrkB and CREB as well as the protein expression of BDNF, TrkB, CREB and p-CREB were decreased in hippocampal CA1 area in the model group (P<0.05); compared with the model group, the mRNA expression of BDNF, TrkB and CREB, the protein expression of BDNF, TrkB and p-CREB as well as the ratio of p-CREB/CREB were increased in the Tongdu Tiaoshen group (P<0.05). CONCLUSION Tongdu Tiaoshen acupuncture can improve the depression-like behavior in PSD rats, the mechanism may be related to the inhibition of oxidative stress in hippocampal tissues and the enhanced activity of CREB/BDNF/TrkB signaling pathway.
Acupuncture Therapy ; Animals ; Brain-Derived Neurotrophic Factor/metabolism* ; Cyclic AMP Response Element-Binding Protein/metabolism* ; Depression/therapy* ; Hippocampus/metabolism* ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Stroke/complications* ; Sucrose ; Superoxide Dismutase

Phyllanthus emblica is a kind of traditional medicine and medicinal and edible plant, with rich variety resources and high development value. It is a key poverty alleviation variety in China at present. As P. emblica processing industry is rising gradually in recent years, in order to fully develop and utilize its industrial resources, this paper systematically introduces current comprehensive development and utilization of P. emblica, discusses the problems in P. emblica processing industry, and puts forward comprehensive development and utilization strategies and industrial models in terms of cultivation, breeding, grading, quality evaluation and waste recycling, so as to provide a certain reference for promoting the high-quality development of P. emblica industry in China.
China ; Medicine ; Medicine, Traditional ; Phyllanthus emblica ; Plant Breeding ; Plant Extracts

Acupuncture Points ; Acupuncture Therapy ; Animals ; Autophagy-Related Proteins ; Depression/therapy* ; Hippocampus ; Phosphatidylinositol 3-Kinase ; Phosphatidylinositol 3-Kinases/genetics* ; Proto-Oncogene Proteins c-akt ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Stroke/therapy* ; TOR Serine-Threonine Kinases

Professor - successively followed famous doctors of acupuncture and spleen-stomach disease, such as -, inherited their academic thoughts and clinical experience, and studied the classics to summarize and propose the clinical academic proposition regulating spleen-stomach differentiating meridians-collaterals. In clinical practice, professor focuses on individual differences of patients, carefully examines syndrome and refines acupoint selection; he pays attention to regulating spleen-stomach, and actively uses Zusanli (ST 36); he simultaneously uses acupuncture-moxibustion and acupoints with efficacy; he inherits traditional reinforcing and reducing methods, and extends the scope of acupoint diagnosis and treatment, while he emphasizes keeping spirit and treating spirit, and the combination of mind and , in order to improve clinical diagnosis and treatment effect.
Acupuncture Points ; Acupuncture Therapy ; Humans ; Male ; Meridians ; Moxibustion ; Spleen ; Stomach

OBJECTIVE: To observe the effects on hippocampal neuronal structure and hippocampal monoamine neurotransmitters such as norepinephrine (NE), 5-hydroxytryptamine (5-HT) and dopamine (DA) with acupuncture for promoting the circulation of the governor vessel and regulating the mental state ( acupuncture) in rats with post-stroke depression and explore the underlying effect mechanism of acupuncture on post-stroke depression. METHODS: A total of 48 clean-grade SD rats were randomized into a sham-operation group, a model group, a Tongdu Tiaoshen acupuncture group and a non-meridian-non-acupoint group, 12 rats in each one. In the model group, the Tongdu Tiaoshen acupuncture group and the non-meridian-non-acupoint group, the compound method of cerebral medial arterial occlusion and the chronic unpredictable mild stress was adopted to prepare the model of post-stroke depression. In the sham-operation group, skin was opened and the fascia muscle was separated, after artery exposed, no ligation was operated and the incision was sutured directly. In the sham-operation group and the model group, no any intervention was performed. In the Tongdu Tiaoshen acupuncture group, acupuncture was applied to "Baihui" (GV 20), "Shuigou" (GV 26), "Shenting" (CV 24) and "Dazhui" (GV 14) for 40 min in each treatment and the needles were manipulated at the acupoints once in 20 min. The treatment was given once a day, 6 times a week for 4 weeks consecutively. In the non-meridian-non-acupoint group, the depression between the 3rd and 4th metatarsal bones on the dorsum of the forelimb was selected in intervention and the needling technique was same as the Tongdu Tiaoshen acupuncture group. The behavioral changes were observed after intervention in each group. Using transmission electron microscopy, the ultrastructure of hippocampal CA 1 neurons was observed in the rats of each group. Using high performance liquid chromatography, the contents of NE, 5-HT and DA were determined. RESULTS: Compared with the sham-operation group, the Zea-longa neurobehavioral score was increased (<0.01), the sucrose water consumption was reduced (<0.01), the number of times of horizontal movement and vertical movement in open-field test were reduced (both <0.01), the damage of the ultrastructure of hippocampal CA 1 neurons was aggravated and the contents of NE, 5-HT and DA were reduced in the model group (<0.01). Compared with the model group, the Zea-Longa neurobehavioral score was reduced (<0.01), the sucrose water consumption was increased (<0.01), the number of times of horizontal movement and vertical movement in open-field test were increased (both <0.01), the damage of the ultrastructure of hippocampal CA 1 neurons was alleviated and the contents of NE, 5-HT and DA were increased in the Tongdu Tiaoshen acupuncture group (<0.01, <0.05). Compared with the non-meridian-non-acupoint group, the Zea-Longa neurobehavioral score was reduced (<0.01), the sucrose water consumption was increased (<0.01), the number of times of horizontal movement and vertical movement in open-field test were increased (both <0.01), the damage of the ultrastructure of hippocampal CA 1 neurons was alleviated and the contents of NE, 5-HT and DA were increased in the Tongdu Tiaoshen acupuncture group (<0.01, <0.05). CONCLUSION The acupuncture improves the behavior of the model rats with post-stroke depression, repairs hippocampal neuronal damage, which is probably related to the contents of hippocampal monoamine neurotransmitters (NE, 5-HT and DA).
Acupuncture Therapy ; Animals ; Depression ; Hippocampus ; Neurons ; Neurotransmitter Agents ; Rats ; Rats, Sprague-Dawley ; Stroke