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

The orbitofrontal cortex (ORB), a region crucial for stimulus-reward association, decision-making, and flexible behaviors, extensively connects with other brain areas. However, brain-wide inputs to projection-defined ORB neurons and the distribution of inhibitory neurons postsynaptic to neurons in specific ORB subregions remain poorly characterized. Here we mapped the inputs of five types of projection-specific ORB neurons and ORB outputs to two types of inhibitory neurons. We found that different projection-defined ORB neurons received inputs from similar cortical and thalamic regions, albeit with quantitative variations, particularly in somatomotor areas and medial groups of the dorsal thalamus. By counting parvalbumin (PV) or somatostatin (SST) interneurons innervated by neurons in specific ORB subregions, we found a higher fraction of PV neurons in sensory cortices and a higher fraction of SST neurons in subcortical regions targeted by medial ORB neurons. These results provide insights into understanding and investigating the function of specific ORB neurons.
Animals ; Neurons/physiology* ; Mice ; Prefrontal Cortex/cytology* ; Parvalbumins/metabolism* ; Brain Mapping/methods* ; Neural Pathways/physiology* ; Somatostatin/metabolism* ; Male ; Interneurons/physiology* ; Mice, Inbred C57BL ; Thalamus/physiology* ; Mice, Transgenic

Objective:To explore the feasibility of deep learning-based restoration of obscured thyroid ultrasound images.Methods:A total of 358 images of thyroid nodules were retropectively collected from January 2020 to October 2021 at Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, and the images were randomly masked and restored using DeepFillv2. The difference in grey values between the images before and after restoration was compared, and 6 sonographers (2 chief physicians, 2 attending physicians, 2 residents) were invited to compare the rate of correctness of judgement and detection of image discrepancies. The ultrasound features of thyroid nodules (solid composition, microcalcifications, markedly hypoechoic, ill-defined or irregular margins, or extrathyroidal extensions, vertical orientation and comet-tail artifact) were extracted according to the Chinese Thyroid Imaging Reporting and Data System (C-TIRADS). The consistency of ultrasound features of thyroid nodules before and after restoration were compared.Results:The mean squared error of the images before and after restoration ranged from 0.274 to 0.522, and there were significant differences in the rate of correctness of judgement and detection of image discrepancies between physicians of different groups(all P<0.001). The overall accuracy rate was 51.95%, the overall detection rate was 1.79%, there were significant differences also within the chief physicians and resident groups (all P<0.001). The agreement rate of all ultrasound features of the nodules before and after image restoration was higher than 70%, over 90% agreement rate for features such as solid composition and comet-tail artifact. Conclusions:The algorithm can effectively repair obscured thyroid ultrasound images while preserving image features, which is expected to expand the deep learning image database, and promote the development of deep learning in the field of ultrasound images.

【Objective】 To investigate the predictive value of nutritional risk index (NRI), systemic immune inflammatory index (SⅡ) and triglyceride glucose (TyG) index on the condition and prognosis of patients with acute pancreatitis (AP). 【Methods】 A total of 173 AP patients were divided into mild acute pancreatitis (MAP) group (n=79), moderate acute pancreatitis (MSAP) group (n=44), and severe acute pancreatitis (SAP) group (n=50) according to their severity. All the 50 SAP patients were divided into death group (19 cases) and survival group (31 cases) according to the death situation. The NRI, SⅡ and TyG indexes of each group were recorded and compared. The values of NRI, SⅡ and TyG index in predicting the occurrence and death of SAP were analyzed with ROC curve. Pearson correlation analysis of the correlation between NRI, SⅡ, and TyG index in SAP patients was made. 【Results】 NRI was significantly lower in SAP group (89.25±4.50) than in MSAP group (93.40±6.25) and MAP group (97.62±8.60), while SⅡand TyG index in SAP group (2 706.30±1 052.74, 7.84±1.21) were significantly higher than those in MSAP group (1 937.24±983.48, 6.52±1.05) and MAP group (1 280.58±717.36, 4.65±0.58) (P<0.001). NRI in death group (86.40±3.70) was significantly lower than that in survival group (91.46±5.28), while SⅡ and TyG index in death group (3 085.73±1 192.48, 9.05±1.37) were significantly higher than those in survival group (2 270.26±994.53, 6.70±1.10) (P<0.001). The ROC curve showed that the AUC of NRI, SⅡ and TyG index jointly predicting SAP occurrence and death was 0.850 (95% CI: 0.792-0.908) and 0.905 (95% CI: 0.843-0.966), respectively. Correlation analysis showed that NRI was negatively correlated with SⅡ and TyG index in SAP patients (r=-0.761, P<0.001, r=-0.813, P<0.001), while SⅡ was positively correlated with TyG index (r=0.842, P<0.001). 【Conclusion】 NRI, SⅡ and TyG index are related to the severity and death of AP patients, and the combination of the three indexes has good value in predicting the occurrence and prognosis of SAP.

Osteoporotic vertebral compression fracture (OVCF) can lead to lower back pain and may be even accompanied by scoliosis, neurological dysfunction and other complications, which will affect the daily activities and life quality of patients. Vertebral augmentation is an effective treatment method for OVCF, but it cannot correct unbalance of bone metabolism or improve the osteoporotic status, causing complications like lower back pain, limited spinal activities and vertebral refracture. The post-operative systematic and standardized rehabilitation treatments can improve curative effect and therapeutic efficacy of anti-osteoporosis, reduce risk of vertebral refracture, increase patient compliance and improve quality of life. Since there still lack relevant clinical treatment guidelines for postoperative rehabilitation treatments following vertebral augmentation for OVCF, the current treatments are varied with uneven therapeutic effect. In order to standardize the postoperative rehabilitation treatment, the Spine Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized relevant experts to refer to relevant literature and develop the "Guideline for postoperative rehabilitation treatment following vertebral augmentation for osteoporotic vertebral compression fracture (2022 version)" based on the clinical guidelines published by the American Academy of Orthopedic Surgeons (AAOS) as well as on the principles of scientificity, practicality and advancement. The guideline provided evidence-based recommendations on 10 important issues related to postoperative rehabilitation treatments of OVCF.

Objective:To investigate the expression level and clinical value of serum miR-148a-3p and miR-551b-5p in patients with acute pancreatitis (AP).Methods:The clinical data of 152 patients with AP admitted to Danzhou people's Hospital from January 2017 to September 2020 were selected. According to the severity of their illness, they were divided into MAP group ( n=70), MSAP group ( n=40), and SAP group ( n=42). The SAP group was divided into survival group ( n=25) and death group ( n=17) according to the prognosis of the patients. Another 50 healthy people were selected as the control group. Fastening venous blood was collected on the day of onset, and the expression levels of serum miR-148a-3p and miR-551b-5p in each group were detected by real-time quantitative PCR. The receiver operating characteristic curve (ROC) was drawn and the area under the curve (AUC) was calculated. The expression levels of serum miR-148a-3p and miR-551b-5p were analyzed to evaluate the prognosis of SAP. The correlation between serum miR-148a-3p and miR-551b-5p expression levels in SAP patients was analyzed by Pearson method. Results:The expression levels of serum miR-148a-3p (3.18±1.27 vs 0.96±0.28) and miR-551b-5p (1.94±0.85 vs 0.51±0.12) in AP group were significantly higher than those in control group ( P<0.001). The expression levels of serum miR-148a-3p (4.36±1.70 vs 2.84±1.10, 2.50±0.92) and miR-551b-5p (2.80±1.04 vs 1.68±0.53, 1.42±0.45) in SAP group were significantly higher than those in MSAP group and MAP group ( P<0.001). The expression levels of serum miR-148a-3p (5.30±1.95 vs 3.47±1.40) and miR-551b-5p (3.62±1.37 vs 2.08±0.91) in death group were significantly higher than those in survival group ( P<0.001). ROC curve analysis showed that the AUC of the combination of miR-148a-3p and miR-551b-5 in judging the prognosis of SAP was significantly higher than that of the single index of miR-148a-3p and miR-551b-5[0.943(95% CI0.886-0.997) vs 0.860(95% CI0.797-0.924), 0.822(95% CI0.795-0.880)], with a sensitivity of 98.3% and specificity of 84.6%. Correlation analysis showed that there were positive correlation between the expression level of serum miR-148a-3p and miR-551b-5p in SAP patients ( r=0.835, P<0.001). Conclusions:The expression levels of miR-148a-3p and miR-551b-5p in serum of AP patients were significantly increased, and the combined detection of miR-148a-3p and miR-551b-5p had a good value in judging the prognosis of SAP.

Objective:To analyze the causes and epidemiological characteristics of an outbreak of brucellosis in Haidong City Qinghai Province, and provide a scientific basis for prevention and control of brucellosis.Methods:Using the retrospective research method, the epidemic data on brucellosis, field case investigations, serological test results in Haidong City, Qinghai Province in 2019 were collected from the "China Disease Prevention and Control Information System", and the above data were analyzed by descriptive epidemiological analysis.Results:There were 3 confirmed brucellosis patients, who were breeders of the farm; 1 case of latent infection was found in key population, who was villager from the same village as the confirmed patients; 4 people had a history of close contact with infected sheep. A total of 110 sheep serum and 7 bovine serum samples were collected in the animal breeding area, of which 26 were positive, all were sheep serum; 568 sheep serum and 17 bovine serum samples in the same village were negative.Conclusions:The key occupational groups contacted with infected sheep without protection is the main cause of this epidemic. Health education on brucellosis prevention and control should be vigorously carried out to improve the awareness of the people to prevent the disease; the monitoring of animal brucellosis by relevant departments should be strengthened to effectively control the spread of animal brucellosis, and prevent the occurrence of human brucellosis.

Objective:To summarize and analyze the clinical data of Chinese patients with colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy, and clarify the phenotypic and genetic characteristics of Chinese patients.Methods:Medical history of patients with CSF1R-related leukoencephalopathy diagnosed from April 1, 2018 to January 31, 2021 in the department of neurology of 22 hospitals in China was collected, and scores of Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment Scale (MoCA), magnetic resonance severity scale were evaluated. Group comparison was performed between male and female patients.Results:A total of 62 patients were included, and the male-female ratio was 1∶1.95. The age of onset was (40.35±8.42) years. Cognitive impairment (82.3%, 51/62) and motor symptoms (77.4%,48/62) were the most common symptoms. The MMSE and MoCA scores were 18.79±7.16 and 13.96±7.23, respectively, and the scores of two scales in male patients (22.06±5.31 and 18.08±5.60) were significantly higher than those in females (15.53±7.41 , t=2.954, P=0.006; 10.15±6.26, t=3.328 , P=0.003). The most common radiographic feature was bilateral asymmetric white matter changes (100.0%), and the magnetic resonance imaging severity scale score was 27.42±11.40, while the white matter lesion score of females (22.94±8.39) was significantly higher than that of males (17.62±8.74 , t=-2.221, P<0.05). A total of 36 CSF1R gene mutations were found in this study, among which c.2381T>C/p.I794T was the hotspot mutation that carried by 17.9% (10/56) of the probands. Conclusions:The core phenotypic characteristics of CSF1R-related leukoencephalopathy in China are progressive motor and cognitive impairment, with bilateral asymmetrical white matter changes. In addition, there exist gender differences clinically, with severer cognitive impairment and imaging changes in female patients. Thirty-six CSF1R gene mutations were found in this study, and c.2381T>C/p. I794T was the hotspot mutation.

Objective To study the relationship of the tibial plateau subchondral trabecular bone (STB) microstructure and the cartilage degeneration with the lower limb alignment based on individual trabecula segmentation (ITS) and histology analysis in knee osteoarthritis (OA). Methods Hip-knee-ankle (HKA) angles were measured on the full-length lower extremity films of patients before total knee arthroplasty (TKA). The tibial plateau excised from the TKA were collected for micro-CT scanning and ITS analysis. The cartilage degeneration was evaluated by histology. The relationship between the HKA angle and the changes in microstructural parameters of STB and cartilage degeneration were analyzed. ResultsThe plate, rod and axial bone trabecular volume fraction (BV/TV, pBV/TV, pBV/TV), ratio of trabecular plate versus rod (P/R), plate trabecular number density (pTb.N), plate trabecular thickness (pTb.Th), trabecular plate surface area (pTb.S), trabecular rod length (rTb.L), and plate-plate and plate-rod junction density (P-P Junc.D, P-R Junc.D) of the subchondral bone of the tibial plateau were significantly related to the cartilage degeneration OARSI score and the HKA angle. The greater the deviation of the lower limb alignment, the greater the number of subchondral trabeculae, the thicker the trabeculae, the greater the bone mass, the stronger the connectivity, especially the plate trabeculae on the affected side of tibial plateau, and the higher the OARSI score of cartilage degeneration. Conclusions Abnormal lower limb alignment may cause abnormal microstructure of the plate and rod STB of the tibial plateau by changing the stress distribution of the knee, especially the significant increase and thickening of the plate trabecular and axial trabecular bone, which may be an important risk factor that further aggravates the degeneration of articular cartilage and the progress of OA. Therefore, lower limb alignment correction with surgical intervention and improving STB with bone metabolism agents may efficiently contribute to preventing cartilage damage and mitigate OA progression.

Objective:To investigate the reproducibility of inflow-based vascular-space-occupancy (iVASO)-MRI in quantifying skeletal muscle perfusion and its potential clinical value in patients with dermatomyositis (DM).Methods:Totally 15 consecutive patients with DM and 15 healthy volunteers were enrolled in this prospective study from December 2018 to April 2019 at Nanfang Hospital, Southern Medical University. All subjects underwent T 1WI, short-tau inversion recovery (STIR) T 2WI, and iVASO-MRI of thigh on a 3.0 T MR scanner. According to findings on T 1WI and STIR T 2WI, the muscles were divided into normal, unaffected, edematous and atrophic or fat-infiltrated groups. Maximum arteriolar muscular blood volume (MBVa_max) and mean MBVa (MBVa_mean) of these 4 groups of muscles were obtained by 2 radiologists independently. In order to evaluate the reproducibility of iVASO, the repeated scan was performed 3 days later in 17 subjects (12 healthy volunteers and 5 DM patients), and the MBVa values were measured to calculate the intraclass correlation coefficients (ICC). The MBVa_max and MBVa_mean among the 4 groups were compared by using Kruskal-Wallis H test and the differences of each 2 groups was compare by using Mann-Whitney U test. Results:The ICC between the 2 observers was 0.95 and 0.96 for MBVa_max and MBVa_mean, respectively. The ICC between repeated tests was 0.87 and 0.89 for MBVa_max and MBVa_mean, respectively.There was significant difference among normal muscles, unaffected muscles, edematous muscles and atrophic or fat-infiltrated muscles ( P<0.001). Post hoc comparisons of MBVa_max and MBVa_mean showed that compared to normal muscles, unaffected muscles, edematous muscles and atrophic or fat-infiltrated muscles had a significant decrease of MBVa ( P<0.05). Unaffected muscles and edematous muscles showed no significant difference in terms of MBVa_max and MBVa_mean (both P=0.99), which were significantly higher than those of atrophic or fat-infiltrated muscles ( P<0.05). Conclusions:iVASO-MRIcan reliably quantify the MBVa of thigh muscular arteriolar, and it is potentially valuable in the diagnosis of DM.