BACKGROUND:In recent years,numerous studies have shown that autophagy and mitophagy play an important role in the regulation of bone metabolism.Under non-physiological conditions,mitophagy breaks the balance of bone metabolism and triggers metabolism disorders,which affect osteoblasts,osteoclasts,osteocytes,chondrocytes,bone marrow mesenchymal stem cells,etc. OBJECTIVE:To summarize the mechanism of mitophagy in regulating bone metabolic diseases and its application in clinical treatment. METHODS:PubMed,Web of Science,CNKI,WanFang and VIP databases were searched by computer using the keywords of"mitophagy,bone metabolism,osteoblasts,osteoclasts,osteocytes,chondrocytes,bone marrow mesenchymal stem cells"in English and Chinese.The search time was from 2008 to 2023.According to the inclusion criteria,90 articles were finally included for review and analysis. RESULTS AND CONCLUSION:Mitophagy promotes the generation of osteoblasts through SIRT1,PINK1/Parkin,FOXO3 and PI3K signaling pathways,while inhibiting osteoclast function through PINK1/Parkin and SIRT1 signaling pathways.Mitophagy leads to bone loss by increasing calcium phosphate particles and tissue protein kinase K in bone tissue.Mitophagy improves the function of chondrocytes through PINK1/Parkin,PI3K/AKT/mTOR and AMPK signaling pathways.Modulation of mitophagy shows great potential in the treatment of bone diseases,but there are still some issues to be further explored,such as different stages of drug-activated mitophagy,and the regulatory mechanisms of different signaling pathways.

OBJECTIVE: To investigate the effects of Huayu Tongluo (transforming stasis and unblocking collaterals) moxibustion on cognitive function and insulin resistance in patients with type 2 diabetes mellitus (T2DM) and cognitive decline. METHODS: Ninety patients with T2DM and cognitive decline were randomly divided into a moxibustion group (n=45, 3 cases dropped out, 2 cases were eliminated) and a waiting moxibustion group (n=45, 2 cases dropped out). Both groups received routine hypoglycemic treatment for 12 weeks. The moxibustion group additionally received Huayu Tongluo moxibustion at Baihui (GV20), Shenting (GV24), and Dazhui (GV14). Pressing moxibustion was applied to Baihui (GV20) for 20 min, while suspended moxibustion was applied to Shenting (GV24) and Dazhui (GV14) for 20 min each. Treatments of moxibustion were administered every other day (three times per week) for 12 weeks. All patients were followed up for 12 weeks, during which their original hypoglycemic medication regimen was maintained. Before treatment, after 12 weeks of treatment, and at the 12-week follow-up, the scores of Montreal cognitive assessment (MoCA), mini-mental state examination (MMSE), Addenbrooke's cognitive examination Ⅲ (ACE-Ⅲ), symbol digit modalities test (SDMT), and Athens insomnia scale (AIS) and the insulin resistance index (HOMA-IR) were observed in the two groups. RESULTS: Compared with before treatment, the MoCA scores, MMSE scores, ACE-Ⅲ subscale scores (attention, memory, language fluency, language, visuospatial ability) and total scores, and SDMT scores were increased (P<0.01), while the AIS scores were decreased (P<0.05) in the moxibustion group after treatment and at follow-up. Compared with before treatment, the MMSE score, ACE-Ⅲ subscale scores (memory, attention) and total score after treatment, as well as the ACE-Ⅲ subscale scores (language, memory, attention) and total score, and SDMT score at follow-up were increased (P<0.05, P<0.01) in the waiting moxibustion group. Compared with before treatment, HOMA-IR was decreased in both groups after treatment and at follow-up (P<0.01). At follow-up, ACE-Ⅲ subscale scores (attention, memory), and the total score in the moxibustion group were lower than those after treatment (P<0.05, P<0.01), and the ACE-Ⅲ language subscale score, total ACE-Ⅲ score, and SDMT score in the waiting moxibustion group were higher than those after treatment (P<0.01, P<0.05). After treatment and at follow-up, compared with the waiting moxibustion group, the moxibustion group had higher MoCA scores, MMSE scores, SDMT scores, ACE-Ⅲ subscale scores (attention, memory, language fluency) and total scores (P<0.05, P<0.01), and lower HOMA-IR (P<0.05). CONCLUSION Huayu Tongluo moxibustion can effectively improve cognitive function in patients with T2DM and cognitive decline. This improvement may be associated with the reduction in insulin resistance.
Humans ; Insulin Resistance ; Diabetes Mellitus, Type 2/complications* ; Male ; Female ; Moxibustion ; Middle Aged ; Aged ; Cognition ; Acupuncture Points ; Adult ; Cognitive Dysfunction/therapy*

Sigma-1 receptor (σ ₁R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K _i < 4 nmol/L) and selective σ ₁R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ ₁R in relation to σ ₂R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ ₁R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.

Objective To study the protective effect of Wedelolactone(WEL)against inflammatory injury in human umbilical vein endothelial cells(HUVECs)and its molecular mechanism by inducing PI3K/Akt/mTOR.Methods The model of atherosclerosis(AS)oxidative stress injury in HUVECs was induced with 200 μmol·L-1 of hydrogen peroxide for 24 h.The experimental groups were as follows:normal control group,DMSO(dimethyl sulfoxide)group,H2O2 group,and WEL group.MTT was used to measure the cell survival rate of each group;flow cytometry was used to assess intracellular ROS levels;fluorescence microscopy was used to detect the expression of p62 protein;immunoblotting assay was used to determine the protein expression levels for apoptosis-related proteins associated with PI3K/Akt/mTOR signaling pathway and autophagy-related proteins.Results Compared with the H2 O2 group,the HUVEC cell survival rate was significantly inhibited in the WEL group(P＜0.05).ROS production was significantly lower,and the protein expressions of SOD1 and p62 were significantly increased in the WEL group as compared to the hydrogen peroxide group.The protein expression of p-mTOR,p-Akt,and p-PI3K was significantly decreased in hydrogen peroxide(P＜0.01);In the WEL experiment,p-mTOR,p-Akt,and p-PI3K were increased significantly in the post-injury HUVECs(P＜0.01).Conclusion Wedelolactone inhibits HUVECs'autophagy by suppressing H2O2-induced inflammatory damage in HUVECs,which may be related to the fact that WEL promotes the phosphorylation of PI3K,Akt,and mTOR proteins,inhibits autophagy and thus resists oxidative stress damage in HUVECs cells.

Objective To investigate the effect of Yu's Qingre Huoxue prescription enema on colonic mucosa in rats with ulcerative colitis(UC).Methods A total of 30 Wistar rats were randomly divided into blank control group,model group,mesalazine group,Chinese medicine high-dose,medium-dose and low-dose groups(5 rats in each group).After successful modeling with trinitrobenzene sulfonic acid,the rats were given 14 days enema with distilled water,mesalazine suspension,and high,medium and low concentration Yu's Qingre Huoxue prescription.The general condition and weight changes of rats were recorded daily,and colon macroscopic damage index(CMDI)and mucosal injury score under microscope of rats in each group were compared.Results Compared with blank control group,the weight of rats in model group decreased significantly(P<0.05).The blank control group had normal water and food intake and activity,glossy fur and normal stool.The rats in model group and each administration group were found to have anal fouling,residual blood in stool,decreased appetite,messy fur,dim luster and other conditions,and the above conditions were gradually improved after enema treatment.Compared with blank control group,the CMDI and mucosal injury scores of model group were significantly increased(P<0.05).Compared with model group,CMDI and mucosal injury scores of mesalazine group and Chinese medicine high-dose,medium-dose and low-dose groups were significantly decreased(P<0.05).Conclusion Yu's Qingre Huoxue prescription can effectively improve the clinical symptoms of diarrhea,mucous,pus and blood stools in UC model rats,reduce the damage of colonic mucosa,promote mucosal repair,and have a good effect on the treatment of UC in rats.

Objective:To observe the 95% effective dose (ED95) of Propofol mono-sedation for successfully inserting the gastroscope in healthy adults by biased coin design up-and-down sequential method.Methods:Using prospective study method, a total of 40 patients proposed for painless gastroscopy in Beijing Friendship Hospital, Capital Medical University from April to May 2021 were selected. There were 15 males and 25 females. American Society of Anesthesiologists (ASA) classification: grade I 26 cases, grade Ⅱ 14 cases. The mean age was (50.80±9.14) years, and the mean body mass index was (24.08±2.65) kg/m 2. Propofol mono-sedation was used in all patients. The initial dose of Propofol was set as 1.6 mg/kg, adjusted with 0.1 mg/kg as a step size. The biased coin design up-and-down sequential method was used in this study. The Propofol dose of subsequent patients was determined by the response to gastroscope insertion of the previous patient. If the gastroscopy insertion reaction of the previous patient was positive, the Propofol dose of the next patient was increased by one level (0.1 mg/kg); if the gastroscopy insertion reaction of the previous patient was negative, the biased coin random was performed, and the Propofol dose used by the next patient was reduced by one level (0.1 mg/kg) with 5% probability and remained unchanged with 95% probability. Changes of mean arterial pressure, heart rate and pulse oxygen saturation were recorded at different time points, and adverse reactions such as perioperative hypotension, bradycardia, tachycardia and hypoxemia were recorded. Measurement data were expressed as mean ± standard deviation ( ± s), and t-test was used for comparison between different time points. The ED95 and 95% CI of Propofol in inhibiting the response to gastroscope insertion was calculated by Probit regression analysis. Results:All 40 patients successfully completed the gastroscopy. The calculated ED95 of Propofol mono-sedation for successfully inserting the gastroscope was 2.58 mg/kg with 95% CI of 2.40-3.31 mg/kg. The mean arterial pressure before anesthesia, after propofol injection, at the time of gastroscopy going through throat and immediately after examination was (97.33±13.34) mmHg, (93.15±11.35) mmHg, (78.95±9.30) mmHg, (79.38±9.94) mmHg (1 mmHg=0.133 kPa), respectively. The mean arterial pressure at the time of gastroscopy going through throat and immediately after examination decreased significantly, the difference was statistically significant ( P<0.01). There were no significant differences in heart rate and pulse oxygen saturation compared with those before anesthesia ( P>0.05). Conclusion:The ED95 of Propofol mono-sedation for successfully inserting the gastroscope is determined as 2.58 mg/kg (95% CI: 2.40-3.31 mg/kg) by biased coin design up-and-down sequential method.

Objective To rationally allocate pharmaceutical and healthcare human resources,and to explore the feasibility of implementing the system of licensed assistant pharmacists in retail pharmacies.Methods Through literature review,questionnaire surveys,and statistical analysis of exam scores,the training status of pharmacy technicians with secondary vocational education,the employment situation in retail pharmacies,and the results of the licensed pharmacist qualification examination were deeply understood.Results Every year,a certain number of graduates with a secondary vocational education in pharmacy entered society,and retail pharmacies were willing to recruit pharmacy technicians with this educational background,their professional competence were recognized.Pharmacy technicians with secondary vocational education can obtain the professional qualification of practicing pharmacists through hard work,and demonstrated the basic competency for working as licensed assistant pharmacists.Conclusion The implementation of the licensed assistant pharmacist system among pharmacy technicians with secondary vocational education in retail pharmacies is feasible.This system can fully leverage the role of pharmacy technicians with secondary vocational education,make up for the shortage of professional personnel in certain regions,promote the construction of the pharmaceutical care system in retail pharmacies,and ensure drug quality and medication safety.

Objective To investigate the design of cuffed pediatric tracheal tubes and compare the effects of different tracheal intubation depth placement strategies on the position of the tracheal tube tip and cuff of 5 tracheal tube brands.Methods A total of 180 children who were admitted to Tianjin Children's Hospital from October 2020 to December 2021,with endotracheal intubation under general anesthesia,aged 1-6 years,were enrolled.The length of the subglottic airway was measured by electronic bronchoscopy.Dimensional data from 5 cuffed pediatric tracheal tube brands were recorded,including the length of the tracheal tube cuff,the distance from the tip of the tracheal tube to the upper edge of the cuff,and the tip of the tracheal tube to the lower edge of the tube glottis marker line the distance.Calculation of the required cuffed endotracheal tube internal diameter(ID)for 180 pediatric patients was performed based on the Motoyama formula,the positions of tracheal tube tip and upper cuff border were calculated for each of the 180 tracheas using depth mark to based tracheal tube placement,placement of the tracheal tube tip at 2 cm above the carina,and mid-tracheal tube placement.Results There were differences in the dimensional data of the 5 cuffed pediatric tracheal tube brands.Depth mark-based tracheal tube placement resulted in the incidence rate of tube tip to carina placement less than 1 cm was 3.9%-67.8%,and the highest incidence of bronchial intubation is Ruijing,up to 17.8%.The tracheal tube tip was placed 2 cm above the carina,and no improper placement of the tracheal tube cuff and tube tip was found in all brands.Mid-tracheal tube placement led to 100%subglottic and supraglottic tracheal tube cuff positions,except Weili.Conclusions There are differences in design between different brands of cuffed pediatric tracheal tube,and some of the design deficiencies may lead to the risk of airway complications.The method used to guide the insertion depth and the brand of cuffed tracheal tubes can affect the tracheal tube position.Placement of the tracheal tube tip at 2 cm above the carina allowed safe tracheal tube placement in children aged 1-6 years.

Objective:This study aimed to explore the clinical value of myostatin(MST) and follistatin(FST) as biological biomarkers in evaluating sarcopenia in elderly women.Methods:This was a retrospective cross-sectional study that enrolled 350 females aged 20-89 years who underwent physical examinations in Shanghai Huadong Hospital in 2021. Demographic characteristics, muscle mass, fat mass, bone mineral density, hand grip strength, gait speed, and serum indices of MST and FST were collected.Results:The serum levels of MST did not change significantly with age. However, the serum levels of FST increased with age. In women aged≥60 years, MST was positively correlated with total lean mass and appendicular skeletal muscle index(ASMI; r=0.236, P=0.041; r=0.289, P=0.014), while FST was negatively correlated with ASMI( r=-0.265, P=0.030). In multivariate stepwise regression analysis, after adjusting for age, body mass index, hip bone mineral density, and total fat mass, only FST was independently correlated with ASMI( β=-0.238, P=0.006), while MST was not correlated with ASMI. The receiver operating characteristic curve was plotted using muscle mass reduction as the state variable and serum FST level as the test variable. The area under the curve was 0.753. And when the FST cutoff value was 17.49 ng/mL, the maximum Jordan index was 0.46, with a sensitivity of 77.3% and a specificity of 68.7%. Women aged ≥60 years were divided into three groups based on serum FST levels. Compared to the upper third of the serum FST level group, the low third of the FST level group had a significantly reduced risk of suffering from sarcopenia( OR=0.098, P =0.036). Conclusions:Serum FST lever has a better correlation with muscle mass among elderly women, making it a promising biomarker for evaluating muscle mass.