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 summarize the clinical characteristics and outcomes of corona virus disease 2019(COVID-19)in patients with adrenal insufficiency(AI),and analyze the risk factors of outcomes.Methods The clinical data of COVID-19 patients with AI in Peking Union Medical College Hospital in December 2022 were ana-lyzed retrospectively and the patients were followed up to collect outcomes of their diseases.Results Among 28 COVID-19 patients with AI,20 cases(71.4%)received basal corticosteroid replacement.Among the 18 patients with community-acquired COVID-19,11 cases(61.1%)increased the corticosteroid dosage proactively at home.The most common symptoms of COVID-19 were fever(96.4%),gastrointestinal symptoms(82.1%)and con-sciousness disturbance(78.6%).Occurrence of severe consciousness disturbance was associated with older age and lower basal corticosteroid replacement dose(P＜0.05). Adrenal crisis(AC)occurred in 20 patients(71.4%),which was associated with lower basal corticosteroid replacement dose,hypochloremia,lower eosinophil,lower platelet,and longer activated partial thromboplastin time(APTT)(P＜0.05). 2 patients died during hospitalization.26.3%(5/19)of surviving patient's recovered consciousness longer than 48 hours.Delayed recovery of conscious-ness was associated with lower systolic pressure,higher blood creatinine,and higher fibrinogen(P＜0.05).Long COVID-19 symptoms such as fatigue and poor appetite occurred in 48.0%(12/25)of patients.Among patients with increased corticosteroid dosage,50.0%(12/24)had their dose reduced to baseline within 3 weeks.Conclusions COVID-19 patients with AI have a high frequency of consciousness disturbance and AC.AI patients are lack of awareness of adjusting corticosteroid dosage proactively in case of infection stress,thus education of"sick day rules"for AI patients should be strengthened in clinical practice.

Objective There are 6 leads of limb lead ECG,and the cardiac electrical axis can be estimated by any combination of two leads.In this paper,the estimation accuracy of all 15 pairs of limb-lead combinations was compared.Methods Using the open database of 12-lead electrocardiograms(at a sampling frequency of 500 Hz with duration of 10 seconds during resting state)from PhysioNet,totally 21 306 ECG records were extracted with age≥18 years which labeled as single sinus type(axis normal),including 6 153 records with Sinus Rhythm,10 916 records with Sinus Bradycardia,3 466 records with Sinus Tachycardia,and 771 records with Sinus Irregularity.Moreover,totally 2 323 axis deflection recordings with age≥18 years were extracted,including 1 526 records with Axis left shift,and 797 records with Axis right shift.Cardiac electrical axis was estimated with the net amplitude(or area)of QRS complex(algebraic sum of positive and negative amplitude or area)by any pair of leads from{Ⅰ,Ⅱ},{Ⅰ,Ⅲ},{Ⅰ,aVR},{Ⅰ,aVL},{Ⅰ,aVF},{Ⅱ,Ⅲ},{Ⅱ,aVR},{Ⅱ,aVL},{Ⅱ,aVF},{Ⅲ,aVR},{Ⅲ,aVL},{Ⅲ,aVF},{aVR,aVL},{aVR,aVF},{aVL,aVF},respectively.Results For the amplitude-based method,the recognition accuracy for the normal,left and right axes from{Ⅰ,Ⅱ}and{Ⅱ,aVL}is 93.56%and 93.50%,respectively,which is better than that of the traditional classical method{I,aVF}(92.93%).For the area-based method,the recognition accuracy from{Ⅲ,aVR},{Ⅰ,aVR},{Ⅰ,Ⅱ},{aVR,aVF},{Ⅱ,aVL}and{Ⅱ Ⅲ}is 92.66%,92.53%,92.29%,92.19%,92.10%and 91.91%,respectively,which is better than the traditional classical method{Ⅰ,aVF}(91.82%).Conclusion The accuracy of amplitude-based method is higher than that of area-based method.Lead pair{Ⅰ,Ⅱ}and{Ⅱ,aVL}have higher accuracy than traditional classical{Ⅰ,aVF}in automatic estimation of cardiac electrical axis for both amplitude and area method.

Objective:To analyze the disease burden in middle-aged and elderly population aged ≥55 in Shenzhen from 2016 to 2030 and provide evidence for the development of healthy aging strategies.Methods:The years of life lost (YLL), years lost due to disability (YLD), and the disability-adjusted life year (DALY) in this population from 2016 to 2022 were calculated. Joinpoint log-linear regression model was used to analyze the time trend. Bayesian age-period-cohort model and grey system model were used to predict YLL, YLD, and DALY in this population in 2030.Results:From 2016 to 2022, the crude DALY rate showed a transient fluctuation in age group 55-74 years, but a pronounced increase in age group ≥85 years. The proportions of YLL and YLD due to non-communicable diseases in all age groups was considerably higher than those due to communicable and nutritional diseases and injuries. In 2022, in all age groups, the YLL due to neoplasms (55-74 years old) and cardiovascular disease (≥75 years old) ranked first, and the YLD due to musculoskeletal disorder ranked first. By 2030, the causes of YLL and YLD ranking first in each age group would be remained, while the ranks of some causes would increase.Conclusions:The age specific characteristics of current and predicted disease burden differed in individuals aged ≥55 years. Therefore, it is necessary to allocate social and medical resources according to the disease burden pattern.

The orphan nuclear receptor Nur77 is emerging as an attractive target for cancer therapy, and activating Nur77's non-genotypic anticancer function has demonstrated strong therapeutic potential. However, few Nur77 site B ligands have been identified as excellent anticancer compounds. There are no co-crystal structures of effective anticancer agents at Nur77 site B, which greatly limits the development of novel Nur77 site B ligands. Moreover, the lack of pharmaceutical ligands restricts Nur77's therapeutic proof of concept. Herein, we developed a first-in-class Nur77 site B ligand (NB1) that significantly inhibited cancer cells by mediating the Nur77/Bcl-2-related apoptotic effect at mitochondria. The X-ray crystallography suggests that NB1 is bound to the Nur77 site B with a distinct binding mode. Importantly, NB1 showed favorable pharmacokinetic profiles and safety, as evidenced by its good oral bioavailability in rats and lack of mortality, bodyweight loss, and pathological damage at the 512.0 mg/kg dose in mice. Furthermore, oral administration of NB1 demonstrated remarkable in vivo anticancer efficacy in an MDA-MB-231 xenograft model. Together, our work discovers NB1 as a new generation Nur77 ligand that activates the Nur77/Bcl-2 apoptotic pathway with a safe and effective cancer therapeutic potency.

Post-traumatic stress disorder (PTSD) is a psychiatric disease that seriously affects brain function. Currently, selective serotonin reuptake inhibitors (SSRIs) are used to treat PTSD clinically but have decreased efficiency and increased side effects. In this study, nasal cannabidiol inclusion complex temperature-sensitive hydrogels (CBD TSGs) were prepared and evaluated to treat PTSD. Mice model of PTSD was established with conditional fear box. CBD TSGs could significantly improve the spontaneous behavior, exploratory spirit and alleviate tension in open field box, relieve anxiety and tension in elevated plus maze, and reduce the freezing time. Hematoxylin and eosin and c-FOS immunohistochemistry slides showed that the main injured brain areas in PTSD were the prefrontal cortex, amygdala, and hippocampus CA1. CBD TSGs could reduce the level of tumor necrosis factor-

OBJECTIVE：To study the prepar ation technology of gastric floating tablets of Schisandra chinensis total lignans （SCTL），and evaluate the quality of prepared tablets. METHODS ：Based on single factor test ，the orthogonal experiment was conducted to optimize the formulation of SCTL gastric floating tablets with the contents of hydroxypropylmethylcellulose （HPMC） K15M，NaHCO3 and microcrystalline cellulose as the factors ，using starting time ，holding time and cumulative release rate of gastric floating tablets as evaluation indexes. The properties ，weight difference ，floatability and accumulative release rate of the prepared SCTL gastric floating tablets were determined. The gastric floating tablets were qualitatively identified by TLC ，and the contents of schisandrin A and total lignans were determined by HPLC and UV spectrophotometry. RESULTS ：The optimal formulation of SCTL gastric floating tablets was made up of 23％ SCTL extract ，20％ HPMC K 15M，40％ microcrystalline cellulose，15％ sodium bicarbonate ，1％ octadecyl alcohol and 1％ polyvinylpyrrolidone. The results of detection of this preparation were in line with the related provisions of “0101 tablet”stated in 2015 edition of Chinese Pharmacopoeia （part Ⅳ）. TLC indicated that the chromatogram of the test sample showed the main spots of same color as the corresponding positions of the chromatogram of schizandrol A control ，Schisandra chinensis reference substance and raw material ，while the negative control has no interference. Content determination results shows that the average content of schizandrol A and total lignans in SCTL gastric floating tablets is 3.187，19.617 mg. It was preliminarily formulated that the content limitation of schizandrol A in one tablet should not be less than 2.50 mg，and the content of total lignans （calculated by schizandrol A ）should not be less than 15.50 mg. CONCLUSIONS：The preparation technology of SCTL gastric floating tablets is stable ，feasible and controllable in quality.

OBJECTIVETo observe the regulatory effects of acupoint electric stimulation on the analgesic substances and the relevant indices of nerve-immunity-endocrine system in the patients undergoing general anesthesia anorectal operation.

METHODSOne hundred and fifty-six patients undergoing hemorrhoids and anal fistula operation were randomized into three groups, 146 cases were included in the analysis. In the No.1 group (48 cases), the conventional intravenous general anesthesia was applied. In the No.2 group (50 cases), besides the conventional intravenous general anesthesia, the acupoint transcutaneous electric stimulation was combined at Neiguan (PC 6), Shenmen (HT 7), Shangliao (BL 31) and Ciliao (BL 32). operation in the No.2 and No.3 groups were lower apparently than that in the No.1 group (<0.05,<0.01).

CONCLUSIONSDuring the general anesthesia anorectal operation, the acupoint transcutaneous electric stimulation achieves analgesic anesthesia through effectively promoting the release of body analgesic substance and reducing the stress level in the operation. With the comprehensive acupoint selection as Neiguan (PC 6) and Shenmen (HT 7) and the local acupoints, the therapeutic effects are better in comparison with the simple selection of local acupoints. In the No.3 group (48 cases), besides the conventional intravenous general anesthesia, the acupoint transcutaneous electric stimulation was combined at Shangliao (BL 31) and Ciliao (BL 32). The electric stimulation was maintained till the end of operation. The patients' saliva was collected 0.5 h before operation and 1 h after operation separately. The indices that reflect the body pain regulation and nerve-immune-endocrine secretion were detected, such as opiophin protein (OPI), secretory immunoglobulin A (SIgA), saliva amylase (sAA), cortisol (Cor) and tumor necrosis factor α (TNF-α). The pain degree was observed 1 h after operation.

RESULTSIn the No.2 group, OPI after operation was higher than that before operation (<0.05). The difference value of OPI in the No.2 group was higher apparently than that in the No.1 group and the No.3 group (both<0.05). SIgA after operation was higher than that before operation in the No.1 group (<0.05). The difference values of SIgA, sAA, Cor in the No.2 group were lower apparently than those in the No.1 group (<0.05,<0.01). TNF-αbefore and after operation and its difference value among the groups were not significant statistically (all>0.05). The pain degrees in 1 h after.

Objective:To detect the effect of microRNA-7 ( miR-7 ) knockdown on pathology in murine acute lung injury ( ALI) model,and preliminarily explore its significance.Methods:Murine ALI model was performed by intraperitoneal injection of Li-popolysaccharide (LPS) (10 mg/kg) into miR-7KD mice and wild-type (wild type,WT) mice respectively.Then,the pathologic injury of lung tissue were observed by HE staining.And total cell count of bronchoalveolarlavage(BAL) was calculated.The relative expression of related cytokines in lung tissue was analyzed by Real-time PCR assay.Furthermore,the changes on proportion of innate immune cells (γδT cell and F4/80 macrophages cell) and adaptive immune cell ( CD4+T cell and CD8+T cell) were analyzed by FACS.Meanwhile, the expression of CD62L and CD69,as well as the absolute number,in CD4+T cell were also analyzed.Results: Compared with WT mice,pathological damage in lung tissues was significantly alleviated in miR-7KD mice.Real-time PCR analysis showed that the relative expression of IL-6 was obviously reduced (P<0.01),conversely,relative expression of IL-4 and TGF-βwere obviously increased (P<0.05).Furthermore,the total cell number in BAL also reduced significantly (P<0.05).Importantly,FACS analysis showed that the proportion and the absolute number of F4/80+Mφcells obviously reduced (P<0.05);however,the proportion of γδT cells increased (P<0.05).Moreover,the proportion and the absolute number of CD4+T cells and CD8+T cells were significantly reduced (P<0.05). Finally, the proportion and the absolute number of CD62L+in CD4+T cells were upregulated vigorously,contrastly,the proportion and the absolute number of CD69+in CD4+T cells were notably up-regulated (P<0.05).Conclusion:miR-7 defeciency could significantly ameliorate the pathology of murine ALI,suggesting that it may play an important regulatory role in the development of ALI.

Objective To apply the virtual reality in balance function training for Parkinson's Disease (PD). Methods From October, 2013 to January, 2016, 31 patients with balance disorders after PD were divided into two groups:the treatment group (n=17) received virtual reality balancing games training, while the control group (n=14) received routine balance training. They were assessed with Berg Balance Scale (BBS), Timed Up and Go Test (TUGT), static fall index (SFI), limits of stability (LOS), dynamic fall index (DFI) and modified Barth-el Index (MBI) before and four weeks after treatment. The frequency of falls in the next six weeks was recorded. Results The scores of BBS, TUGT, SFI, LOS, DFI and MBI improved significantly in both groups after treatment (P<0.05), and improved more in scores of BBS (t=2.095), TUGT (t=-2.091), DFI (t=-2.182), LOS scores (t=2.202) and MBI (t=3.036) in the treatment group than in the control group (P<0.05). There was positive correlation between scores of BBS and MBI (r=0.899, P<0.001). The frequency of falls was less in the treatment group than in the control group (P<0.05). Conclusion Virtual reality balance training can improve the balance function for PD.