Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

Objective:To detect the expression level of tRF-31-PER8YP9LON4VD in the serum of breast cancer patients and to explore its effect on the function of breast cancer cells.Methods:The serums of 57 breast cancer patients, 39 breast benign tumor patients and 40 normal physical examination patients in the Affiliated Cancer Hospital of Nanjing Medical University from April to August in 2022 were collected. Real-time quantitative polymerase chain reaction(RT-qPCR) to detect the expression level of tRF-31-PER8YP9LON4VD in breast cancer cell lines and serum of breast cancer patients. Cell invasion assay, migration assay and CCK-8 proliferation assay were used to analyze the effect of tRF-31-PER8YP9LON4VD on breast cancer cell function. The receiver operating characteristic curve (ROC) curve was used to analyze the diagnostic efficacy of tRF-31-PER8YP9LON4VD in serum in breast cancer. The chi-square test was used to analyze the correlation between tRF-31-PER8YP9LON4VD and clinical features.Results:The expression levels of tRF-31-PER8YP9LON4VD in breast cancer cell lines MDA-MB-231 (0.50±0.22 vs 1.00±0.01), T-47D (0.33±0.02 vs 1.00±0.01) and MCF-7 (0.50±0.02 vs 1.00±0.01) were significantly lower than those in normal mammary epithelial cell lines (1.00±0.01), and the difference was statistically significant (all P<0.05). The expression level of tRF-31-PER8YP9LON4VD in the serum of breast cancer patients (1.35±1.25) was lower than that in the serum of patients with normal physical examination (6.42±3.13) and patients with benign breast tumors (9.57±2.11), and the difference was statistically significant (both P<0.001). Compared with the control group, the invasiveness of overexpressing tRF-31-PER8YP9LON4VD T-47D (86.67±12.22 vs 532.00±22.68, P<0.001) and MDA-MB-231 (535.33±99.12 vs 1 055.67±24.00, P=0.002) was weaker, and that of T-47D (442.67±81.79 vs 1 210.67±115.02, P=0.002) and MDA-MB-231 (278.67±108.40 vs 571.33±95.37, P=0.015) had weaker migration ability, and T-47D and MDA-MB-231 had weaker proliferative ability (all P<0.05). The area under the curve of serum tRF-31-PER8YP9LON4VD for the diagnostic efficacy of breast cancer was 0.743 (95% CI 0.644-0.842), and the sensitivity and specificity were 89.50% and 53.10%, respectively. Conclusion:tRF-31-PER8YP9LON4VD is low expressed in the serum of breast cancer patients, and it may inhibit the proliferation, migration and invasion of breast cancer cells.

Post-amputation pain causes great suffering to amputees, but still no effective drugs are available due to its elusive mechanisms. Our previous clinical studies found that surgical removal or radiofrequency treatment of the neuroma at the axotomized nerve stump effectively relieves the phantom pain afflicting patients after amputation. This indicated an essential role of the residual nerve stump in the formation of chronic post-amputation pain (CPAP). However, the molecular mechanism by which the residual nerve stump or neuroma is involved and regulates CPAP is still a mystery. In this study, we found that nociceptors expressed the mechanosensitive ion channel TMEM63A and macrophages infiltrated into the dorsal root ganglion (DRG) neurons worked synergistically to promote CPAP. Histology and qRT-PCR showed that TMEM63A was mainly expressed in mechanical pain-producing non-peptidergic nociceptors in the DRG, and the expression of TMEM63A increased significantly both in the neuroma from amputated patients and the DRG in a mouse model of tibial nerve transfer (TNT). Behavioral tests showed that the mechanical, heat, and cold sensitivity were not affected in the Tmem63a^-/- mice in the naïve state, suggesting the basal pain was not affected. In the inflammatory and post-amputation state, the mechanical allodynia but not the heat hyperalgesia or cold allodynia was significantly decreased in Tmem63a^-/- mice. Further study showed that there was severe neuronal injury and macrophage infiltration in the DRG, tibial nerve, residual stump, and the neuroma-like structure of the TNT mouse model, Consistent with this, expression of the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β all increased dramatically in the DRG. Interestingly, the deletion of Tmem63a significantly reduced the macrophage infiltration in the DRG but not in the tibial nerve stump. Furthermore, the ablation of macrophages significantly reduced both the expression of Tmem63a and the mechanical allodynia in the TNT mouse model, indicating an interaction between nociceptors and macrophages, and that these two factors gang up together to regulate the formation of CPAP. This provides a new insight into the mechanisms underlying CPAP and potential drug targets its treatment.
Animals ; Mice ; Amputation, Surgical ; Chronic Pain/pathology* ; Disease Models, Animal ; Ganglia, Spinal/pathology* ; Hyperalgesia/etiology* ; Ion Channels/metabolism* ; Macrophages ; Neuroma/pathology*

Humans ; Lymphoma, T-Cell, Cutaneous/complications* ; Neuroglia ; Pruritus/pathology* ; Skin Neoplasms/complications* ; Spinal Cord/pathology* ; Sympathetic Nervous System

Objective:To analyze the efficacy and safety of Daratumumab for the treatment of primary AL light chain systemic amyloidosis.Methods:Twenty one patients who were diagnosed as primary AL light chain systemic amyloidosis and treated with Daratumumab from 7 centers were retrospectively analyzed. Daratumumab was administrated as first line therapy in seven patients and 14 patients with relapsed settings. Hematological response, safety and survival were analyzed.Results:All 7 patients achieved very good partial response (VGPR) or better with first-line application of daratumumab. Three patients died, and the other four achieved organ remission. Among 14 relapsed patients, 2 patients had a difference of free light chain (dFLC) less than 20 mg/L before treatment, and 9 with a dFLC of more than 50 mg/L. All patients reached partial response (PR) or better, including 4 patients with complete response (CR), 3 with VGPR and 2 with PR. The response rate was 100% in 3 patients with dFLC 20-50 mg/L at baseline. The organ remission rate was 50% in patients with heart involvement and 58.3% in patients with kidney impairment. The overall median follow-up period was 5.3 months, and 11 months in surviving patients. One patient died of severe infection and disseminated intravascular coagulation (DIC) with stable amyloidosis. One patient switched to other regimens because dFLC elevated but did not fulfill progressive disease after 2 year application. As to safety, no grade 3/4 infusion reaction developed, and grade 1 infusion reaction occurred in 3 cases during the first infusion. Lymphocytopenia was seen in 75% patients including grade 3 or more in 30% patients.Conclusion:Daratumumab is effective to eliminate serum free light chain in both newly diagnosed and relapsed patients with systemic amyloidosis.

Objective: To explore the clinical effect of Huoxue Qing Gong decoction in the treatment of vaginal bleeding after medical abortion. Methods: From May 2016 to June 2017, 90 cases of vaginal bleeding after drug abortion in the People's Hospital of Dongping County were divided into the observation group and the control group according to the digital table, with 45 cases in each group.The two groups were all treated with drug abortion to terminate pregnancy, and the control group was treated with metronidazole tablets + carbazochrome tablets after the termination of pregnancy.The observation group was treated with Huoxue Qing Gong decoction on the basis of the control group.The effect of abortion, bleeding time and bleeding volume after drug abortion, the time of menstrual recovery and menstrual duration after treatment in the two groups were observed and compared. Results: The total abortion rate in the observation group was 95.6%, which was significantly higher than that in the control group(84.4%), the difference was statistically significant(χ²=5.620, P<0.05). The proportion of bleeding time≤7d after abortion in the observation group was 37.8%, which was significantly higher than that in the control group(11.1%), the difference was statistically significant(χ²=5.628, P<0.05). The proportion of bleeding time 8~14d of the observation group was 60%, which was significantly lower than that of the control group(73.3%), the difference was statistically significant(χ²=6.571, P<0.05). The proportion of bleeding time more than 15d after drug abortion of the observation group was 2.2%, which was significantly lower than that of the control group(15.6%), the difference was statistically significant(χ²=5.028, P<0.05). The proportion of vaginal bleeding volume2=6.021, P<0.05). The proportion of amount of vaginal bleeding=previous menstrual volume after drug abortion in the observation group was 22.2%, which was significantly lower than that in the control group(26.7%), the difference was statistically significant (χ²=5.114, P<0.05). The proportion of vaginal bleeding volume>previous menstrual volume after drug abortion of the observation group was 17.8%, which was significantly lower than that of the control group(44.4%), the difference was statistically significant(χ²=6.375, P<0.05). The period of menstrual recovery of the observation group was (29.5±4.2)d, which was significantly shorter than that of the control group[(37.9±4.3)d](t=5.028, P<0.05). The duration of menstruation in the observation group was (5.0±1.1)d, which was significantly shorter than that in the control group[(6.9±1.2)d], the difference was statistically significant(t=3.229, P<0.05). Conclusion Huoxue Qing Gong decoction in the treatment of vaginal bleeding after drug abortion can significantly shorten the time of vaginal bleeding, reduce the amount of vaginal bleeding, improve the rate of complete abortion, and has no obvious effect on the first menstrual cycle and menstrual period after the drug flow.

Objective To explore the mechanisms of ligament of Marshall (LOM) initiat and sustain atrial fibrillation (AF).Methods The electrophysiologic properties of canine LOM were investigated using multipolar catheter mapping(normal canines,n =4,group A;AF canines,n =5,group B).The programmed stimulation were performed in the LOM,PV-left atrium(LA)junction and LA,respectively.Activations maps of LOM were analyzed from episodes of spontaneous onset of AF and initiation of induced AF by a single extrastimulus.The effectives refractory period of each part was compared and statistically analyzed among three parts in each group and between the two groups.LOM were cutted with surgical incision technology.The inducing rate of AF and the mapping rate of double potential and fragmented electrocardiogram were compared and statistically analyzed pro and post isolation of LOM.Results The incidence of abnormal potential of LOM in the two groups was significantly different(P ＜0.01),re-entry cycle(group A 25％ vs.B group 80％),tachycardia(group A 25％ vs.B 100％),double potential(group A 25％ vs.group B 80％),fragmentation potential(group A 25％ vs.group 80％).There was a significant difference in the rate of LOM tachycardia induction before and after LOM intervention in group B (P ＜ 0.05,before 100％ vs.after 20％).Conclusion There are two possible mechanisms of LOM involved in the occurrence and maintenance of AF:one is that LOM induces AF through spontaneous excitation,the other is that LOM participates in the reentry of left atrium and pulmonary vein in the form of bypass to induce and maintain AF.

Objective To explore the status quo of workplace bullying and job satisfaction among clinical nurses, and to explore the mediating effect of peer support among nurses in the relationship between the above two elements.Methods By convenience sampling, from November 2015 to April 2016, 207 clinical nurses in a comprehensive classⅢ grade A hospital in Fuzhou, were selected and surveyed by a questionnaire on general information, a peer support scale, the negative acts questionnaire-revised (NAQ-R), and job satisfaction scale for nurses. Correlation analysis and regression analysis were conducted to the data collected.Results Workplace bullying was significantly negatively related with peer support among nurses(r=-0.395,P<0.01), and job satisfaction (r=-0.338,P<0.01). Peer support among nurses was positively correlated with job satisfaction (r=0.611, P<0.01). Among nurses, peer support was the mediating variable between workplace bullying and job satisfaction. After introduction of peer support among nurses, influence of workplace bullying on job satisfaction was statistically meaningless (β=-0.148,t=-1.716,P>0.05).Conclusions In the relationship between workplace bullying and job satisfaction, peer support among nurses plays a role as a full mediation. Nursing managers should actively introduce the idea of peer support among nurses, lower workplace bullying, and improve job satisfaction among nurses.

Objective To observe effects of problem-based learning(PBL) combined with case-based study (CBS)teaching mode in clinical teaching in intensive care unit(ICU). Methods Students from ICU of Fangcun Branch of Guangdong Provincial Hospital of Traditional Chinese Medicine from March 2011 to February 2012 were divided into treatment group (31 cases, with PBL combined with CBS teaching mode) and control group (34 cases, with the traditional teaching mode). Scores of two groups were compared and analyzed and questionnaire survey was conducted in treatment group. Data were processed by SPSS 13.0 statistical software. Measurement data were compared by t-test and data of heterogeneous variance were compared by rank-sum test. Results Treatment group achieved better scores ((85.26 ±5.96) in theory examination and (80.59 ±7.33) in case-analyzing examination) compared with those of control group ((79.17 ±7.31) in theory examination and (76.02 ±9.27) in case-analyzing examination)(P<0.05). PBL combined with CBS teaching mode can stimulate learning interests but it was lack of systematization; most students did not volunteer to speak. Conclusion PBL combined with CBS teaching mode has certain advantages in ICU clinical teaching.

Objective To observe the seroreversion of serological tests for syphilis in neonates born to mothers with syphilis and to evaluate the influence of antisyphilitic treatment on the time of seroreversion in uninfected neonates.Methods A total of 115 neonates born to mothers with syphilis were recruited in this study,and underwent toluidine red unheated serum test (TRUST),Treponema pallidum particle assay (TPPA)and 19S IgM-TPPA at birth.Follow up was scheduled at 1,3,6,9,12,18 and 24 months of age,and cancelled as soon as both TRUST and TPPA became negative during the 24 months.Both TRUST and TPPA were carried out at each follow-up visit.Kaplan-Meiter survival analysis and Wilcoxon rank-sum test were conducted to assess these data by using SPSS 13.0 software.Results At birth,TPPA was positive in all (100％) of the neonates,TRUST in 97 neonates (84.3％) with the titer ranging from 1 ∶ 1 to 1 ∶ 256,19S IgM-TPPA in 3 neonates who were diagnosed with congenital syphilis (CS).CS was ruled out in the other 112 neonates with negative 19S IgM-TPPA after follow up.Of the 3 neonates with CS,all became negative for TRUST within 12-18 months after birth,2 remained positive for TPPA at 24 months of age,1 remained positive for TPPA at 20 months of age,and all were still followed at the time of this writing.The cumulative seroreversion rate was 82.2％,98.9％ and 100％for TRUST at 0-3,4-6 and 7-9 months of age,respectively in 90 uninfected neonates,3.1％,30.2％,85.4％ and 100％ for TPPA at 0-3,4-6,7-9 and 10-12 months of age,respectively in 96 uninfected neonates.Of 16 neonates who missed some follow-up visits,all turned negative for TRUST and TPPA within 15 months after birth.As far as the TP-seropositive uninfected neonates were concerned,no statistical differences were observed in the seroreversion time of TRUST or TPPA between neonates receiving antisyphilitic treatment and those without antisyphilitic treatment (x2 =0.54,2.41,respectively,both P ＞ 0.05).The seroreversion of TRUST occurred earlier than that of TPPA (Z =10.45,P ＜ 0.01).Conclusions Most uninfected neonates born to syphilitic mothers turn negative for TRUST within 6 months after birth,and for TPPA within 12 months.And the seroreversion of TRUST usually occurs earlier than that of TPPA.Antisyphilitic treatment shows no significant influence on the seroreversion time of TRUST or TPPA in these seropositive uninfected infants.