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

Background/Aims: The shortage of donor liver hinders the development of liver transplantation. This study aimed to clarify the poor outcomes of functionally marginal liver grafts (FMLs) and provide evidence for the improvement of ischemia-free liver transplantation (IFLT) after FML transplantation. Methods: Propensity score matching was used to control for confounding factors. The outcomes of the control group and FML group were compared to demonstrate the negative impact of FMLs on liver transplantation patients. We compared the clinical improvements of the different surgical types. To elucidate the underlying mechanism, we conducted bioinformatic analysis based on transcriptome and single-cell profiles. Results: FMLs had a significantly greater hazard ratio (HR: 1.969, P=0.018) than did other marginal livers. A worse 90-day survival (Mortality: 12.3% vs. 5.0%, P=0.007) was observed in patients who underwent FML transplantation. Patients who received FMLs had a significant improvement in overall survival after IFLT (Mortality: 10.4% vs 31.3%, P=0.006). Pyroptosis and inflammation were inhibited in patients who underwent IFLT. The infiltration of natural killer cells was lower in liver grafts from these patients. Bulk transcriptome profiles revealed a positive relationship between IL-32 and Caspase 1 (R=0.73, P=0.01) and between IL-32 and Gasdermin D (R=0.84, P=0.0012). Conclusions FML is a more important negative prognostic parameter than other marginal liver parameters. IFLT might ameliorate liver injury in FMLs by inhibiting the infiltration of NK cells, consequently leading to the abortion of IL-32, which drives pyroptosis in monocytes and macrophages.

Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.

Disorders of sex development (DSD) are a group of rare complex clinical syndromes with multiple etiologies. Distinguishing the various causes of DSD is quite difficult in clinical practice, even for senior general physicians because of the similar and atypical clinical manifestations of these conditions. In addition, DSD are difficult to diagnose because most primary doctors receive insufficient training for DSD. Delayed diagnoses and misdiagnoses are common for patients with DSD and lead to poor treatment and prognoses. On the basis of the principles and algorithms of dynamic uncertain causality graph (DUCG), a diagnosis model for DSD was jointly constructed by experts on DSD and engineers of artificial intelligence. "Chaining" inference algorithm and weighted logic operation mechanism were applied to guarantee the accuracy and efficiency of diagnostic reasoning under incomplete situations and uncertain information. Verification was performed using 153 selected clinical cases involving nine common DSD-related diseases and three causes other than DSD as the differential diagnosis. The model had an accuracy of 94.1%, which was significantly higher than that of interns and third-year residents. In conclusion, the DUCG model has broad application prospects as a computer-aided diagnostic tool for DSD-related diseases.

Objective : To observe the changes of soft tissue in patients with Angle class Ⅱ division Ⅰ malocclusion during mixed dentition treated with MRC functional appliance. Methods : Twenty patients with Class Ⅱ division Ⅰ malocclusion of Angle were treated with functional MRC. The facial features before and after treatment were measured by software and the results were analyzed statistically. Results: The patients′soft tissue profiles were improved significantly before and after treatment, The OE-Prn-Pos angle, OE-N′-B′ angle, OE-N′-Pos angle, OE-Prn-N′angle, Cm-Sn-UL angle, and N′-Sn-Pos angle increased significantly (P < 0.05). The OE-Sn-UL angle, and Sn-N′-B′ angle decreased significantly (P < 0.05); the distance between the lateral soft tissue line and the middle Sn-H line, UL-E line and LL-E line were significantly different (P < 0.05). The distances were all reduced, and the difference was statistically significant (P < 0.05). Conclusion The application of an MRC functional appliance can improve the relationship among nasolabial soft tissue, upper and lower lip soft tissue, and chin-lip soft tissue, thus improving the protrusion profile of patients.

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 investigate the efficacy and safety of IA regimen which contains idarubicin (IDA) 8 mg/m², 10 mg/m² or 12 mg/m² as induction chemotherapy for adult patients with de-novo acute myeloid leukemia (AML) . Methods: A total of 1 215 newly diagnosed adult AML patients, ranging from May 2011 to March 2015 in the First Affiliated Hospital of Soochow University and other 36 clinical blood centers in China were enrolled in the multicenter, single-blind, non-randomized, clinical controlled study. To compare the response rate of complete remission (CR) , adverse events between different dose idarubicin combined with cytarabine (100 mg/m²) as induction chemotherapy in newly diagnosed patients of adult AML. Results: Of 1 207 evaluable AML patients were assigned to this analysis of CR rate. The CR rates of IDA 8 mg/m² group, IDA 10 mg/m² group and IDA 12 mg/m² group were 73.6% (215/292) , 84.1% (662/787) and 86.7% (111/128) , respectively (P<0.001) . After adjusted for age, blast ratio of bone marrow, FAB classification and risk stratification, the odds ratios (95% CI) of IDA 10 mg/m² group and IDA 12 mg/m² group were 0.49 (0.34-0.70) and 0.36 (0.18-0.71) , as compared with the IDA 8 mg/m² group (P<0.001, P=0.003) . In the intermediate and favorable groups, CR rates was 76.5% (163/213) , 86.9% (506/582) and 86.1% (68/79) in different doses of IDA (P=0.007) . Interestingly, IA regimen with IDA 10 mg/m² was the only beneficial factor affecting CR in this group after adjusted for age, blast ratio of bone marrow and FAB classification[OR=0.47 (95% CI 0.31-0.71) , P<0.001]. CR rates in adverse group was 50.0% (18/36) , 60.6% (43/71) and 81.8% (18/22) respectively (P=0.089) . However, the odds ratios (95% CI) of IDA 12 mg/m² when compared with the IDA 8 mg/m² was 0.22 (0.06-0.80) , after adjusted for age, blast ratio of bone marrow and FAB classification. The median time (days) of neutrophil count less than 0.5×10⁹/L in IDA 8 mg/m² group, IDA 10 mg/m² group and IDA 12 mg/m² group were 14 (11-18) , 15 (11-20) and 18 (14-22) , respectively (P=0.012) and of platelet count lower than 20×10⁹/L were 14 (7-17) , 15 (11-20) and 17 (15-21) , respectively (P=0.001) . The incidences of lung infection in the three groups were 9.8%, 13.5% and 25.2%, respectively (P<0.001) . Conclusions For young adult patients (aged 18-60 years) with AML in China, intensifying induction therapy with idarubicin 10 mg/m² is clinically superior to IDA 8 mg/m² and IDA 12 mg/m² in favorable intermediate AML subgroup. However, idarubicin 12 mg/m² is more suitable to adverse AML subgroup.

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 investigate the effect of interferon-γ(IFN-γ) on the expression of indoleamine 2,3-dioxygenase(IDO),and tryptophanyl-tRNA-synthetase (TTS) in thyrocytes; and to study the relevant immunopathological significance in Graves' disease.Methods The expressions of IDO and TTS genes in IFN-γ stimulated Nthy-ori3-1 cell line and human thyrocytes,as well as in human thyroid tissues were determined by realtime quantitative PCR.Results IDO and TTS genes were expressed slightly in both Nthy-ori3-1 cell line and human thyrocytes,and were significantly up-regulated after IFN-γ stimulation(P＜0.01).Compared to healthy controls,TTS mRNA level was higher in thyroid tissues of patients with Graves' disease (P =0.018 2),while IDO mRNA level showed no difference,but was notably correlated with IFN-γ mRNA level (R2 =0.716,P =0.002).Conclusion In the early stage of Graves' disease,thyrocytes may decompose local tryptophan by enhancing the expression of IDO and TTS under IFN-γstimulation,thus inhibit auto-reactive function of lymphocytes and balance excessive autoimmune reaction.

Objective To seauch the ideal management for gross hematuria in autosomal dominant polycystic kidney disease (ADPKD).Methods ADPKD patients who were ever hospitalized and followed up in our department since 1993 were enrolled in the study.Demographic and clinical data were colloected,such as gender,age of gross hematuria,level of renal function,causative factors,management strategies,duration of gross hematuria,blood platelet count,activated partial thromboplastin time,prothrombin time,international normalized ratio,size of kidney cyst and so on.ADPKD patients were divided into different groups according to causative factors or management.The clinical data were compared among groups.Results A total of 905 ADPKD patients were screened,among whom 279 patients ever had gross hematuria (male/female:150/129),One hundred and forty-six patients had integrated therapeutic process records,while only 101patients could provide relevant laboratory examination results.In these 101 patients,gross hematuria was found in any stage of chronic kidney disease (CKD); the average eGFR was (56.4±44.1) mml·min-1 ·(1.73 m2)-1; the duration of gross hematuria was (8.8±8.0) d; no significant difference between male and female in duration of gross hematuria existed [(8.2±7.3) d vs (9.5±8.8) d,P=0.426]; coagulation parameters were all normal.The platelet count was also normal in 91 patients.Duration of gross hematuria among groups divided according to different causative factors was significantly different (P＜0.05).The patients in bed rest group had significantly shorter duration of gross hematuria compared with other groups (P＜0.05).The platelet count,prothromhin time and international normalized ratio were all at similar level in different groups.Conclusions The causative factors in ADPKD patients with gross hematuria should be confirmed as the first step of management strategies.Bed rest is the key point in management.Antifibrinolytic agent is a proper choice in the cases receiving bemostatic drugs.It is unnecessary to use antibiotic agent for prevention.