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

Traumatic rib fractures are the most common injury in thoracic trauma. Previously，the patients with traumatic rib fractures were mostly treated non-surgically，of which 50%，especially those combined with flail chest presented chronic pain or chest wall deformities and over 30% had long-term disabilities，being unable to retain a full-time job. In the past two decades，thanks to the development of internal fixation material technology，the surgical treatment of rib fractures has achieved good outcomes. However，there are still some problems in clinical treatment，including inconsistency in surgical treatment and quality control in medical services. The current consensuses on the management of regional traumatic rib fractures published at home and abroad mainly focus on the guidance of the overall treatment decisions and plans，and relevant clinical guidelines abroad lacks progress in surgical treatment of rib fractures in recent years. Therefore，the Chinese Society of Traumatology affiliated to Chinese Medical Association and Chinese College of Trauma Surgeons affiliated to Chinese Medical Doctor Association，in conjunction with national multidisciplinary experts，formulate the Chinese Consensus for Surgical Treatment of Traumatic Rib Fractures（2021）following the principle of evidence-based medicine，scientific nature and practicality. This expert consensus puts forward some clear，applicable，and graded recommendations from aspects of preoperative imaging evaluation，surgical indications，timing of surgery，surgical methods，rib fracture sites for surgical fixation，internal fixation methods and material selections，treatment of combined injuries in rib fractures，in order to provide references for surgical treatment of traumatic rib fractures.

Objective To assess the efficacy and safety of 100 mg or 200 mg yimitasvir phosphate combined with sofosbuvir in patients with non-cirrhotic chronic hepatitis C virus ( HCV) genotype 1 infection who were treatment-na?ve or had a virologic failure to prior interferon-based treatment.Methods A multicenter, randomized, open-label, phase 2 clinical trial was conducted.The patients were randomly assigned to yimitasvir phosphate 100 mg+sofosbuvir 400 mg group (Group 100 mg) and yimitasvir phosphate 200 mg+sofosbuvir 400 mg group ( Group 200 mg) in a 1∶1 ratio with the stratified factors of " treatment-naive" or"treatment-experienced" for 12 weeks and followed up for 24 weeks after the end of treatment.During the clinical trial, HCV RNA was tested in all patients.Resistance of virus in patients who didn′t achieved sustained virological response (SVR) was monitored.Safety and tolerability were assessed by monitoring adverse events , physical examination , laboratory examination, electrocardiogram, and vital signs during the study.The primary end point was SVR12 after the end of therapy.Descriptive statistics were used for categorical variables and eight descriptive statistics were used for continuous variables.Descriptive statistics were used and summarized according to HCV genotypes and treatment groups.Safety data were presented using descriptive statistics and summarized according to treatment groups.Results A total of 174 subjects were screened from July 31, 2017 to September 26, 2018.One hundred and twenty-nine patients were successfully enrolled and received treatment , and 127 completed the study.There were 64 patients and 65 patients assigned to Group 100 mg and Group 200 mg, respectively.Among the 129 patients who underwent randomization and were treated , 18.6% were treatment-experienced and: 100%were HCV genotype 1b infection.The total SVR rate was 98.4%(127／129), with 98.4%(63／64, 95%confidence interval [CI]: 91.60%-99.96%) in the Group 100 mg, and 98.50%(64／65, 95%CI: 91.72%-99.96%) in the Group 200 mg.There was no significant difference between the two groups (χ2 ＝0.000 2, P＝0.989 2).The SVR rates in treatment-naive group and treatment-experienced group were 98.10%(95%CI: 93.29%-99.77%) and 100.00%(24／24, 95%CI: 85.75%-100.00%), respectively.Virological failure during treatment ( including breakthrough , rebound and poor efficacy) and relapse after treatment did not occur during the trial.By Sanger sequencing , 11.6%(15／129) patients had baseline NS5A Y93H／Y or Y93H resistance-associated substitutions ( RAS), 1.6%( 2／129) patients had baseline NS5A L31M RAS.No mutation was observed in NS5B S282 at baseline.There was no S282 mutation in HCV NS5B.A total of 100 (77.5%) subjects had adverse events.No adverse events ≥Grade 3 or severe adverse events related to the study treatment.No patient prematurely discontinued study treatment owing to an adverse event.No life-threatening adverse event was reported.Conclusion Twelve weeks of yimitasvir phosphate 100 mg or 200 mg combined with sofosbuvir 400 mg daily is a highly effective and safe regimen for patients without cirrhosis with HCV genotype 1b infection who had not been treated previously or had a virologic failure to prior interferon-based treatment.

Objective To expound emphatically the application of nuclear medical examination in primary hyperparathyroidism.Methods 22 patients (19 adenomas,3 hyperplasia) with primary hyperparathyroidism confirmed by clinical examination and surgery underwent the detection of parathormone (PTH) by immunoradiometric assay (IRMA) and double phase 99 Tcm-MIBI parathyroid imaging,of whom 15 performed 99 TcmO-4 thyroid imaging and 8 99 Tcm-MDP bone imaging.Results The level of serum PTH in all patients (428.21±256.48) was significantly higher as compared to normal value and in cases with adenomas (781.83±194.56) was markedly elevated.The sensitivity of 99 Tcm-MIBI early and delayed phase imaging in detecting lesions of parathyroid adenomas was 84.2% and 100%,respectively.The sensitivity in detecting lesions of hyperplasia was only 33.3%.With 99 Tcm-O-4 thryoid imaging,the cold nodules were present in 2 and normality in 13.As to bone imaging,the scans were abnormal in 7.Their severities on bone scintigraph were correlated with the duration of the disease.Conclusions The level of serum PTH detected by IRMA and double phase 99 Tcm-MIBI parathyroid imaging are both sensitive methods in qualitative diagnosis and localization of hyperthyroidism.99Tcm-MIBI imaging has limited value for detecting the hyperplasia.The thyroid and bone imaging may well improve the diagnostic sensitivity and accuracy,and reflect the stage and progress of hyperparathyroidism.

AIM: The aim of this study was to observe the cardiac performance in 2-week or 4-week levothyroxine(T4)-induced cardiac hypertrophy and to elucidate the possible underlying mechanism of cardiac hypertrophy transition to heart failure in T4 treatment rats.METHODS: The blood pressure and pulse rate were measured by tail-cuff technique.The cardiac output and the preload-cardiac output were measured in working heart mode.The shortening of unloading contraction in cardiomyocytes was observed by an edge-detector system.RESULTS: Resting heart rate in T4 treatment rats increased significantly and the width of cardiomyocytes widened in T4 rats,but the length of cardiomyocytes had no difference compared with control values.The cardiac output in 2-week T4 group was higher than that in control group.The cardiac output increased when the preload increased from 5 mmHg to 15 mmHg.The unloading shortening amplitude at 1 Hz and 2 Hz increased in 2-week T4 group.No difference between 2-week T4 group and control group at 4 Hz was observed.When the stimulating frequency increased from 1 Hz to 4 Hz,the shortening amplitude also increased in control cardiomyocytes,but decreased in 2-week or 4-week T4 group.The shortening amplitude increased further in 4-week T4 group as compared with that in control.The time to peak shortening and time from peak shortening to 75% relaxation reduced at each frequency in 2-week and 4-week T4 group.The shortening and relaxation rates in 2-week or 4-week T4 group were higher than those in control group at 1 Hz and 2 Hz.The shortening and relaxation rate kept higher at 4 Hz in 2-week T4 group,but showed no difference with control at 4 Hz in 4-week T4 group.CONCLUSION: These above results suggest that shortening amplitude-frequency relationship of cardiomyocytes in 4-week T4 rats is earlier to be altered than cardiac performance in working heart.

It is kno wn that 8-Br-cAMP is one of selective bi nding site analogues for cAMP RIIα to af fect cell growth through regulation of g ene expression.The p16,p21wafl,p53 a nd Rb are antioncogenes which affect cel l growth through control of cell cycle.T he aim of this study is to investigate t he 8-Br-cAMP effect on the expression of antioncogenes in human HXO-Rb44 cells. Methods Cultured HXO-Rb44 cells in RPMI -1 640 medium were divided into two aliquot s.8-Br-cAMP (2×10-5mol/L) was added i nto one aliquot for 24h as the experime ntal group(EG),the another aliquot witho ut 8-Br-cAMP as the control group(CG).Af ter 24h,the cell suspension was dropped onto the nitrocellulose membrane.The mR NA of p16,p21wafl,wild type(w)p53,mut ant type(m) p53 and Rb were used respec tively with biotin-labeled cDNA probes b y intact cell RNA dot blot.The immunorea ctivity(IR) of P16,P21wafl,PRb,PCN A,cdk2 and cdk4 were detected respecti vely with specific monoclonal antibodies on dot blot.ResultsThe mRNA dot blot s ignals of mp53 and protein dot blot of cdk2-IR,cdk4-IR and PCNA-IR in EG were weaker than those in CG(P＜0.05～0.01). W hile,the mRNA signals of p16,p21wafl,wp53 and Rb in EG were stronger than tho se in CG(P＜0.05～0.01).The intensity of ea ch protein dot blot was consistent with that of their RNA dot blot (except for w P53-IR and mP53-IR not to be done).Conc lusions(1)8-Br-cAMP could up-regul ate expression of antioncogenes includin g p16,p21wafl,wp53,Rb,and protein exp ression of P16,P21wafl and PRb.(2) 8-Br-cAMP could down-regulate mp53 gene expression and protein expression of cd k2,cdk4 and PCNA.The results suggest t hat 8-Br-cAMP could inhibit human HXO-Rb 44 cell growth through interfering rela ted gene expression of cell cycle.

Objective To evaluate the value of measurement of the width of pars compacta of substantia nigra(SNc) and SNc's ratio to midbrain diameter in diagnosing Parkinson's disease(PD) and differentiating PD from vascular parkinsonism(VP) on routine MRI.Methods The width of SNc, midbrain diameter, and SNc's ratio to midbrain diameter were measured in 60 patients with PD (38 patients with Hoehn-Yahr stage Ⅰ～Ⅱ, 14 patients with Hoehn-Yahr stage Ⅲ, and 8 patients with Hoehn-Yahr stage Ⅳ), 60 patients with VP (26 patients with Hoehn-Yahr stage Ⅰ～Ⅱ, 20 patients with Hoehn-Yahr stage Ⅲ, and 14 patients with Hoehn-Yahr stage Ⅳ), and 60 age-matched heathly control subjects by means of routine axial T 2-weighted MRI. The results of measurement were analyzed and compared.Results Significant reduction was found in the width of SNc and SNc's ratio to midbrain diameter in PD compared those in VP and control subjects(P