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 evaluate the role of lactate dehydrogenase in diabetic neuropathic pain (DNP) and the relationship with peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in mice.Methods:SPF-grade healthy male C57BL/6J mice, aged 6-8 weeks, weighing 18-22 g, were used to establish diabetes mellitus model by intraperitoneal injection of streptozotocin (STZ) 120 mg/kg. Twenty-four mice with diabetes mellitus were divided into 2 groups ( n=12 each) using a random number table method: DNP group and DNP + oxamate group (OXA group). Another 12 SPF-grade healthy male C57BL/6J mice were selected as control group (C group). In OXA group, oxamate 750 mg/kg was intraperitoneally injected once a day for 28 consecutive days. The equal volume of normal saline was given instead in C group and DNP group. The mechanical paw withdrawal threshold (MWT), blood glucose and body weight were measured at 3 days before STZ injection and at 1, 2, 3 and 4 weeks after STZ injection (T 0-4). After the last behavioural test was completed, blood samples were collected from the posterior orbits of anesthetized mice for determination of serum lactate concentrations. The animals were then sacrificed and the tissues from the prefrontal cortex of the brain were taken for determination of lactate content, mitochondrial membrane potential (by the JC-1), content of reactive oxygen species (ROS) (using dihydroethidium probes), and level of histone lactylation and expression of PGC-1α (by Western blot). Results:Compared with C group, the MWT was significantly decreased at T 2-4, the serum lactate concentrations, contents of lactate and ROS and level of histone lactylation were increased, the mitochondrial membrane potential was decreased, and the expression of PGC-1α was down-regulated in DNP and OXA groups ( P<0.05). Compared with DNP group, no significant change was found in blood glucose and body weight ( P>0.05), the MWT was significantly increased at T 2-4, the serum lactate concentrations, contents of lactate and ROS and level of histone lactylation were decreased, the mitochondrial membrane potential was increased, and the expression of PGC-1α was up-regulated in OXA group ( P<0.05). Conclusions:Lactate dehydrogenase promotes the development of DNP, and the mechanism is related to promotion of increase in histone lactfication and down-regulation of PGC-1α expression in the prefrontal cortex of mice.

ObjectiveTo explore the syndrome elements and evolving patterns of patients with hepatitis B virus-related acute on chronic liver failure （HBV-ACLF） at different stages. MethodsClinical information of 1,058 hospitalized HBV-ACLF patients， including 618 in the early stage， 355 in the middle stage， and 85 in the late stage， were collected from 18 clinical centers across 12 regions nationwide from January 1， 2012 to February 28， 2015. The “Hepatitis B-related Chronic and Acute Liver Failure Chinese Medicine Clinical Questionnaire” were designed to investigate the basic information of the patients， like the four diagnostic information （including symptoms， tongue， pulse） of traditional Chinese medicine （TCM）， and to count the frequency of the appearance of the four diagnostic information. Factor analysis and cluster analysis were employed to determine and statistically analyze the syndrome elements and patterns of HBV-ACLF patients at different stages. ResultsThere were 76 four diagnostic information from 1058 HBV-ACLF patients， and 53 four diagnostic information with a frequency of occurrence ≥ 5% were used as factor analysis entries， including 36 symptom information， 12 tongue information， and 5 pulse information. Four types of TCM patterns were identified in HBV-ACLF， which were liver-gallbladder damp-heat pattern， qi deficiency and blood stasis pattern， liver-kidney yin deficiency pattern， and spleen-kidney yang-deficiency pattern. In the early stage， heat （39.4%， 359/912） and dampness （27.5%， 251/912） were most common， and the pattern of the disease was dominated by liver-gallbladder damp-heat pattern （74.6%， 461/618）； in the middle stage， dampness （30.2%， 187/619） and blood stasis （20.7%， 128/619） were most common， and the patterns of the disease were dominated by liver-gallbladder damp-heat pattern （53.2%， 189/355）， and qi deficiency and blood stasis pattern （27.6%， 98/355）； and in the late stage， the pattern of the disease was dominated by qi deficiency （26.3%， 40/152） and yin deficiency （20.4%， 31/152）， and the patterns were dominated by qi deficiency and blood stasis pattern （36.5%， 31/85）， and liver-gallbladder damp-heat pattern （25.9%， 22/85）. ConclusionThere are significant differences in the distribution of syndrome elements and patterns at different stages of HBV-ACLF， presenting an overall trend of evolving patterns as "from excess to deficiency， transforming from excess to deficiency"， which is damp-heat → blood stasis → qi-blood yin-yang deficiency.

Objective:To evaluate the role of spinal cord neuron Src-associated-in-mitosis-68-kDa (SAM68)-transient receptor potential vanilloid-1 channel (TRPV1) signaling pathway in diabetic neuropathic pain (DNP) in mice.Methods:Forty SPF male C57BL/6 mice, aged 8 weeks, weighing 18-22 g, were used in this study. Diabetes mellitus was induced by intraperitoneal streptozotocin 0.12 mg/g, and successful DNP model was defined as decrease in the mechanical paw withdrawal threshold (MWT) of the hind limb≥50% of the baseline value. Twenty-four mice with DNP at 4 weeks after developing the model were divided into 3 groups ( n=8 each) using a simple random sampling: DNP group, SAM68 knocked down group (KD group) and virus control group (VC group). Eight diabetic mice with decrease in MWT <50% were randomly selected as non-DNP group (ND group), and 8 normal mice were randomly selected as control group (NC group). At 4 weeks after developing the diabetes mellitus model, SAM68 gene silencing virus and empty virus were injected into the lumbar enlargement of the spinal cord in KD group and VC group, respectively. MWT was measured before developing the diabetes mellitus model and at 4 and 6 weeks after developing the diabetes mellitus model. The mice were sacrificed after the end of MWT measurement at week 6 after developing the model, spinal cord tissues were collected and the expression of SAM68 and TRPV1 was detected by Western blot, and their localization in the spinal cord was observed by immunofluorescence. Results:Compared with NC and ND groups, the MWT was significantly decreased at 4 and 6 weeks after developing the model, and the expression of SAM68 and TRPV1 in spinal cord tissues was up-regulated in DNP group ( P<0.05). Compared with DNP group, the MWT was significantly increased at 6 weeks after developing the model, the expression of SAM68 and TRPV1 in spinal cord tissues was down-regulated, and no significant change was found in the parameters mentioned above in VC group ( P>0.05). SAM68 and TRPV1 were expressed in neurons in the same region of the spinal cord. Conclusions:Activation of SAM68-TRPV1 signaling pathway in spinal cord neurons is involved in the pathophysiological mechanism of DNP in mice.

Objective:To analyze the status of respiratory pathogen detection and the clinical features in children with Mycoplasma pneumoniae pneumonia (MPP). Methods:A prospective, multicenter study was conducted to collect clinical data, including medical history, laboratory examinations and multiplex PCR tests of children diagnosed with MPP from 4 hospitals in China between November 15 th and December 20 th, 2023. The multiplex PCR results and clinical characteristics of MPP children in different regions were analyzed. The children were divided into severe and mild groups according to the severity of the disease. Patients in the severe group were further divided into Mycoplasma pneumoniae (MP) alone and Multi-pathogen co-detection groups based on whether other pathogens were detected besides MP, to analyze the influence of respiratory pathogen co-detection rate on the severity of the disease. Mann-Whitney rank sum test and Chi-square test were used to compare data between independent groups. Results:A total of 298 children, 136 males and 162 females, were enrolled in this study, including 204 children in the severe group with an onset age of 7.0 (6.0, 8.0) years, and 94 children in the mild group with an onset age of 6.5 (4.0, 7.8) years. The level of C-reactive protein, D-dimer, lactic dehydrogenase (LDH) were significantly higher (10.0 (5.0, 18.0) vs. 5.0 (5.0, 7.5) mg/L, 0.6 (0.4, 1.1) vs. 0.5 (0.3, 0.6) mg/L, 337 (286, 431) vs. 314 (271, 393) U/L, Z=2.02, 2.50, 3.05, all P<0.05), and the length of hospitalization was significantly longer in the severe group compared with those in mild group (6.0 (6.0, 7.0) vs. 5.0 (4.0, 6.0) d, Z=4.37, P<0.05). The time from onset to admission in severe MPP children was significantly shorter than that in mild MPP children (6.0 (5.0, 9.5) vs. 9.0 (7.0, 13.0) d, Z=2.23, P=0.026). All patients completed the multiplex PCR test, with 142 cases (47.7%) MPP children detected with 21 pathogens including adenovirus 25 cases (8.4%), human coronavirus 23 cases (7.7%), rhinovirus 21 cases (7.0%), Streptococcus pneumoniae 21 cases (7.0%), influenza A virus 18 cases (6.0%). The pathogens with the highest detection rates in Tianjin, Shanghai, Wenzhou and Chengdu were Staphylococcus aureus at 10.7% (8/75), adenovirus at 13.0% (10/77), adenovirus at 15.3% (9/59), and both rhinovirus and Haemophilus influenzae at 11.5% (10/87) each. The multi-pathogen co-detection rate in severe MPP children was significantly higher than that in mild MPP group (52.9% (108/204) vs. 36.2% (34/94), χ2=10.62, P=0.005). Among severe MPP children, there are 89 cases in the multi-pathogen co-detection group and 73 cases in the simple MPP group. The levels of LDH, D-dimer and neutrophil counts in the multi-pathogen co-detection group were significantly higher than those in the simple MPP group (348 (284, 422) vs. 307 (270, 358) U/L, 0.8 (0.5, 1.5) vs. 0.6 (0.4, 1.0) mg/L, 4.99 (3.66, 6.89)×10 9vs. 4.06 (2.91, 5.65)×10 9/L, Z=5.17, 4.99, 6.11, all P<0.05). Conclusions:The co-detection rate of respiratory pathogens, LDH and D-dimer in children with severe MPP were higher than those with mild MPP. Among severe MPP children the stress response of children in co-detection group was more serious than that of children with simple MPP.

Objective:To observe the role of Huaiqihuang Granules (HQ) in the long-term management of bronchial asthma in young children, and the effective effect on concomitant rhinitis.Methods:A prospective real-world multicenter study was conducted in children aged 2-5 years with asthma diagnosed in the outpatient department (from April 2016 to March 2019)who received either inhaled corticosteroid (ICS)/leukotriene receptor antagonist (LTRA)(control group); inhaled ICS/LTRA plus HQ(combination group), or HQ alone(HQ group). All patients were followed up at week 4, 8, 12 after treatment. The number of days with asthma symptoms, the frequency of severe asthma attacks, the level of asthma control, and the days with rhinitis symptoms in the last 4 weeks were recorded. Differences before and after treatment, and those among groups after treatment were compared using Kruskal- Wallis H test or Wilcoxon rank-sum test. Results:A total of 2 234 eligible patients were recruited, and 2 147 cases completed followed-up visits, including 477, 1 374 and 296 cases in the control group, combination group, and HQ group, respectively. After the treatment, all 3 groups showed significant declines in the days with asthma symptoms, frequency of severe asthma attack and the days with rhinitis symptoms (all P<0.01), and the rate of well-controlled asthma increased significantly ( P<0.01). It lasted until the end of follow-up. Among groups, patients in the combination group showed significantly less days of asthma symptoms than those of the other 2 group at week 8 and 12[0(0, 0.9) d vs.0(0, 0.3) d, P<0.05; 0(0, 0.1) d vs. 0(0, 1.0) d, P<0.01]. Patients in the combination group and HQ group showed a significantly lower rate of severe asthma attacks than that of the control group at week 12 [0(0, 1), 0(0, 1), 0(0, 2), all P<0.05]. The well-controlled rate of asthma in the combination group was significantly higher than that of the control group and HQ group at week 8 and 12 (89.6% vs. 85.9% vs.82.1%, H=15.28; 90.9% vs. 84.1% vs. 81.8%, χ2=29.32, all P<0.01). Conclusions:HQ can significantly alleviate symptoms of asthma and rhinitis, severe attack of asthma, and increase the control rate of asthma when used as an additional treatment or used alone.

Objective:To explore the risk factors of acute kidney injury(stage 3)developed within 48 hours in elderly patients with sepsis, and to use them to develop a risk prediction model and then evaluate and externally validate the model.Methods:Clinical data of all elderly patients(age≥ 60 years)with sepsis in the intensive care medicine information database(MIMIC-Ⅳ v1.0)were extracted.Independent risk factors were determined by multivariate logistic regression analysis.A risk prediction model was constructed, a nomogram was drawn, and the receiver operating characteristic curve(ROC)and the Hosmer-Lemeshow(H-L)test were used to evaluate the model's prediction accuracy and R-squared.Clinical data of elderly patients(age≥ 60 years)with sepsis admitted to the Department of Critical Care Medicine of the Second People's Hospital of Hefei from May 2019 to October 2021 were retrospectively collected and fed into the prediction model to conduct external validation.Results:A total of 1 977 elderly patients with sepsis were screened out from the MIMIC-IV database and included in the training set, of whom, 544 developed AKI-stage 3 within 48 hours.Univariate analysis was performed for factors that might be associated with acute kidney injury in elderly patients with sepsis.Compared with the normal group that did not progress to AKI stage 3, there were statistically significant differences in 28 indicators, such as the duration of ICU stay, intravenous fluid intake in 24 hours, and use of vasoactive drugs[5(3, 9)d vs.7(4, 12)d; 2.05(1.17, 3.27)ml·kg -1·h -1vs.2.37(1.47, 4.10)ml·kg -1·h -1; 761(53.11%) vs.375(68.93%), P<0.001]. Based on the results of multivariate logistic regression analysis, a prediction model was finally constructed with 9 variables: albumin( OR=0.983, 95% CI: 0.966-0.999, P=0.040), aspartate transaminase( OR=1.000, 95% CI: 1.000-1.000, P<0.001), APTT( OR=1.005, 95% CI: 1.001-1.009, P=0.028), total bilirubin( OR=1.003, 95% CI: 1.001-1.004, P=0.001), serum creatinine( OR=1.005, 95% CI: 1.004~1.007, P<0.001), Charlson score( OR=1.117, 95% CI: 1.061-1.177, P<0.001), intravenous fluid intake in 24 hours( OR=1.101, 95% CI: 1.034-1.173, P=0.003), weight( OR=1.023, 95% CI: 1.018-1.029, P<0.001), and mechanical ventilation( OR=2.412, 95% CI: 1.843-3.157, P<0.001). Then a nomogram was generated.The area under the ROC curve(AUC)of the prediction model was 0.755(95% CI: 0.731-0.780), and the H-L test was conducted( χ2=10.89, P=0.208>0.05), indicating a good fit.Data from 102 elderly patients were included in the validation set, with 27 cases that had developed AKI-stage3 within 48 hours, and were fed into the prediction model, with an AUC of 0.778(95% CI: 0.676-0.880)and χ2=3.72 and P=0.882>0.05 from the H-L test, consistent with the results of the training set. Conclusions:The model has some predictive value for acute kidney injury in elderly patients with sepsis.

Objective:To evaluate the effect of metformin preconditioning on adenosine monophosphate-activated protein kinase(AMPK)/PTEN-induced putative protein kinase(PINK1) signaling pathway during ischemia-reperfusion (I/R) injury in diabetic rats.Methods:Thirty-six clean-grade healthy male Sprague-Dawley rats, aged 6 weeks, weighing 120-160 g, were divided into 3 groups ( n=12 each) by the random number table method: diabetic sham operation group (DS group), diabetic myocardial I/R group (DI/R group) and diabetic myocardial I/R+ metformin preconditioning group(DI/R+ Met group). After 4 weeks of feeding a high-fat and high-glucose diet, the model of type 2 diabetes mellitus was induced by a single intraperitoneal injection of 1% streptozotocin 40 mg/kg. The myocardial I/R injury was induced by blocking the anterior descending branch of the left coronary artery for 30 min followed by 120-min reperfusion in anesthetized animals. In DI/R+ Met group, metformin 200 mg/kg was given by intragastric gavage once a day within 1 week before myocardial ischemia. Blood samples from the femoral vein were collected at 120 min of reperfusion for determination of the serum creatine kinase isoenzymes (CK-MB) and cardiac troponin I (cTnI) concentrations by enzyme-linked immunosorbent assay. Then the rats were sacrificed and myocardial tissues were obtained for examination of the pathological changes(by HE staining) and for determination of the percentage of myocardial infarct size (by the double staining of Ewan blue and TTC) and expression of myocardial autophagy-related protein Beclin-1, PTEN-induced putative kinase 1 (PINK1), phosphorylated 5′-adenosine monophosphate-activating protein kinase (p-AMPK), and ratio of microtubule-associated protein 1 light chain 3Ⅱ/Ⅰ (LC3Ⅱ/Ⅰ) (by Western blot). Results:Compared with DS group, the percentage of myocardial infarct size and serum CK-MB and cTnI concentrations were significantly increased, the expression of Beclin-1, p-AMPK and PINK1 in myocardial tissues was up-regulated, the ratio of LC3II/I was increased( P<0.05), and the pathological changes were aggravated in DI/R group and DI/R+ Met group. Compared with DI/R group, the percentage of myocardial infarct size and serum CK-MB and cTnI concentrations were significantly decreased, the expression of Beclin-1, p-AMPK and PINK1 in myocardial tissues was up-regulated, the ratio of LC3Ⅱ/Ⅰ was increased ( P<0.05), and the pathological changes were significantly reduced in DI/R+ Met group. Conclusions:The mechanism by which metformin preconditioning reduces myocardial I/R injury is related to activation of AMPK/PINK1 signaling pathway and up-regulation of mitochondrial autophagy in diabetic rats.

Hypoxemia is a common complication of pneumonia, asthma, and bronchopulmonary dysplasia in children.Rapid identification of hypoxemia is of great significance for the disposal and management of critical children.Pulse oximetry is recognized by the World Health Organization as the best way to monitor hypoxemia in children, and it can monitor pulse oxygen saturation noninvasively and continuously.Based on the related literature at home and abroad, combined with the clinical needs of pediatrics, the " Expert consensus on clinical application of pulse oximetry in children" is formulated to improve the understanding of pediatricians and nurses on the application in pediatric clinical practice, principle, operation techniques, and limitations of pulse oximetry.

Objective:To investigate the knowledge, attitudes, and practices (KAP) of pulse oximetry among pediatric healthcare providers in China and analyze the factor influencing the KAP.Methods:A self-developed questionnaire was used for an online research on the KAP of 11 849 pediatric healthcare providers from 31 provinces, autonomous regions, and municipalities of China from March 11 to 14, 2022.The factors influencing the KAP of pulse oximetry among pediatric healthcare providers were examined by Logistic regression. Results:The scores of KAP, of pulse oximetry were 5.57±0.96, 11.24±1.25 and 11.19±4.54, respectively.The corresponding scoring rates were 69.61%, 74.95%, and 55.99%, respectively. Logistic regression results showed that the gender and working years of pediatric healthcare providers, the region they were located, and whether their medical institution was equipped with pulse oximeters were the main factors affecting the knowledge score (all P<0.05). Main factors influencing the attitude score of pediatric healthcare providers included their knowledge score, gender, educational background, working years, region, medical institution level, and whether the medical institution was equipped with pulse oximeters (all P<0.05). For the practice score, the main influencing factors were the knowledge score, gender, age, and whether the medi-cal institution was equipped with pulse oximeters (all P<0.05). Conclusions:Chinese pediatric healthcare providers need to further improve their knowledge about and attitudes towards pulse oximetry.Pulse oximeters are evidently under-used.It is urgent to formulate policies or guidelines, strengthen education and training, improve knowledge and attitudes, equip more institutions with pulse oximeters, and popularize their application in medical institutions.