Mitophagy,a critical regulator of knee joint homeostasis,its dysfunction can lead to pathological changes such as reactive oxygen species overproduction,calcium ion overload,and extracellular matrix degradation,inducing cartilage degeneration and serving as a key pathological mechanism of knee osteoarthritis(KOA)."Deficient qi stagnation"represents the core pathogenesis of KOA.Mitochondria,analogous in function to qi and serving as its microscopic manifestation,exhibit a high degree of congruence between mitophagy and the defensive functions of qi.Based on the pathogenic characteristics of"deficient qi stagnation"of KOA,and integrating modern medical explanations of mitophagy,this article believed that the deficiency of liver,spleen and kidney qi is the fundamental reason for the imbalance of mitochondrial autophagy in KOA,and the retention of pathogenic toxins is the key factor in the imbalance of mitochondrial autophagy.The basic treatment method of tonifying qi and strengthening the body,promoting blood circulation and promoting stagnation can provide clinical formula ideas for the TCM prevention and treatment of KOA.

Objective: To explore the associations of moderate to vigorous intensity physical activity (MVPA) and sedentary behavior (SB) among primary and secondary school students and their parents, so as to provide a scientific basis for formulating targeted physical activity promotion strategies for children and adolescents. Methods: From 2021 to 2022, basic information and 24 h movement behaviors of 2 484 pairs of students and their parents were collected from five primary and secondary schools in Haizhu District, Guangzhou City, with a convenient sampling combining with cluster sampling method. Component regression models were constructed to analyze the relationship between parental MVPA, SB and primary and secondary school students MVPA and SB, and a component isochronous substitution model was used to explore the effects of mutual substitution between parental MVPA, residual components (time use components other than SB during the 24 h period), and SB on the behavioral activities of MVPA and SB in primary and secondary school students. Results: Parental MVPA and SB of students in grade 1 to 3 were positively correlated with both students MVPA and SB ( β=0.06, 0.12, P <0.01). The component isochronous substitution model showed that substituting 10 and 20 minutes of MVPA for SB by parents in grade 1 to 3 was associated with an increase in MVPA of students, and substituting 10 and 20 minutes of residual ingredients for SB was associated with a decrease in SB of students, with mean changes of 0.8 (95% CI =0.4-1.2) and 1.4 (95% CI =0.7-2.2) and -1.4 (95% CI =-1.7 to -1.1) and -2.9 (95% CI =-3.4 to -2.3)( P <0.05). No statistically significant associations were observed between parents of students in grades 4 to 6 and 7 to 9 and students physical activity and sedentary behaviour ( P >0.05). Conclusions Parents of students in grades 1 to 3 increases MVPA and decrease SB are beneficial to increase MVPA and decrease SB of students. Parents could promote physical activity among primary and secondary school students, and the intervention gateway should be advanced, with the low grades as the optimal intervention period.

Mitophagy,a critical regulator of knee joint homeostasis,its dysfunction can lead to pathological changes such as reactive oxygen species overproduction,calcium ion overload,and extracellular matrix degradation,inducing cartilage degeneration and serving as a key pathological mechanism of knee osteoarthritis(KOA)."Deficient qi stagnation"represents the core pathogenesis of KOA.Mitochondria,analogous in function to qi and serving as its microscopic manifestation,exhibit a high degree of congruence between mitophagy and the defensive functions of qi.Based on the pathogenic characteristics of"deficient qi stagnation"of KOA,and integrating modern medical explanations of mitophagy,this article believed that the deficiency of liver,spleen and kidney qi is the fundamental reason for the imbalance of mitochondrial autophagy in KOA,and the retention of pathogenic toxins is the key factor in the imbalance of mitochondrial autophagy.The basic treatment method of tonifying qi and strengthening the body,promoting blood circulation and promoting stagnation can provide clinical formula ideas for the TCM prevention and treatment of KOA.

ObjectiveTo investigate the mechanism by which Liuwei Dihuang Erzhiwan combination inhibit the lung metastasis of spontaneous breast cancer in mice by regulating the recruitment of myeloid-derived suppressor cells （MDSCs）. MethodThree hundred and eighty SPF-grade 10-month-old female breeders of Kunming mouse were palpated at the mammary gland site once every 3 days. Mice that have not had a lump touched after being raised for 6 months are used as control group. After tumor development， the mice were randomized into model， positive control （paclitaxel， intraperitoneal injection at 0.01 g·kg^-1 every other day for 22 d）， Liuwei Dihuangwan （0.65 g·kg^-1·d^-1 by gavage）， Erzhiwan （5.41 g·kg^-1·d^-1 by gavage）， and Liuwei Dihuang Erzhiwan combination （6.05 g·kg^-1·d^-1 by gavage） groups. The mice were euthanised when the tumor reached a diameter of about 15 mm， and the tumor and lung tissues were collected. The survival time， tumor mass， and lung metastasis rate of tumor-bearing mice were recorded. Hematoxylin-eosin （HE） staining was used to observe the histopathological and morphological changes of mouse tumor and lung tissues. Immunofluorescence （IF） was used to detect the distribution of MDSCs in tissues of mice in each group by double-staining of MDSCs cells with lymphocyte antigen 6 complex site G6D （Ly6G） and CD11 antigen-like family member B （CD11b）. Western blot was employed to determine the protein levels of matrix metalloproteinase-9 （MMP-9）， transforming growth factor-β （TGF-β）， zinc finger transcription factor 1 （Snail1）， and E-cadherin in the tumor tissue and CC motif chemokine 9 （CCL9） and CC motif chemokine receptor 1 （CCR1） in the lung tissue. ResultDuring the modelling period， the paclitaxel group and Chinese medicine intervention groups had longer median number of days of survival and lower tumor weight， lung metastasis rate， and lung nodule than the model group （P<0.05， P<0.01）. HE staining showed an increase in tumor cell necrosis in the paclitaxel group and the Liuwei Dihuang Erzhiwan combination group. The paclitaxel group and Chinese medicine intervention groups had lower fluorescence intensity of MDSCs in the tumor tissue than the model group （P<0.05， P<0.01）. Compared with the normal control group， the model group showed increased fluorescence intensity of MDSCs in the metastatic lung tissue （P<0.01）， which， however， was decreased in the paclitaxel group and Chinese medicine intervention groups （P<0.01）. The model group showed higher protein levels of MMP-9， TGF-β， and Snail1 and lower protein level of E-cadherin in the tumor tissue than in the normal control group （P<0.01）. Compared with model group， paclitaxel and Chinese medicine interventions downregulated the protein levels of MMP-9， TGF-β， and Snail1 （P<0.05， P<0.01） and upregulated the protein level of E-cadherin in the tumor tissue （P<0.01）. Moreover， the Liuwei Dihuang Erzhiwan combination group had lower protein levels of TGF-β and Snail1 than the Liuwei Dihuangwan group and Erzhiwan group （P<0.05）. In the metastatic lung tissue， the expression of CCL9 and CCR1 was higher in the model group than in the normal control group， paclitaxel group， and Chinese medicine intervention groups （P<0.05， P<0.01）. ConclusionLiuwei Dihuang Erzhiwan combination inhibit tumor growth， prolong survival time， and reduce the occurrence of lung metastasis in the mouse model of spontaneous breast cancer by reducing the recruitment of MDSCs in the tumor and lung tissues and modulating the phenotypes of epithelial-mesenchymal transition （EMT）-related molecules and the expression of CCL9/CCR1.

Anxiety disorders are common mental disorders often accompanied by varying degrees of dysfunction. However, its causes and related pathological mechanisms are still unclear. In recent years, many studies have found abnormalities in the cerebellar structure and function of patients with anxiety disorders, with significant heterogeneity observed among different subtypes of anxiety disorders. This article reviews the studies on cerebellar imaging features in patients with different subtypes of anxiety disorders, exploring potential research directions on the pathogenesis of anxiety disorders from both structural and functional perspectives.

Opioid receptors μOR,δOR,κOR and NOPR are all G protein-coupled receptors(GPCRs),which mainly function through G protein and β-ar-restin.Recent studies have found that G protein mediates analgesia,while β-arrestin reduces anal-gesia and is related to the side effects of opioids.Oliceridine is the first biased μOR agonist approved for commerce.It mainly exerts analgesic effect by activating G protein.It has rapid onset of action and reliable analgesic effect.Due to its low activity on β-arrestin,the incidence of side effects is low,comparing to the classic opioid morphine.Oliceri-dine can be safely used in patients with liver or kid-ney insufficiency and its metabolite is inactive.This article summarizes the current progress of pharma-cological research and clinical application of oliceri-dine,aiming to provide reference for the clinical practice of oliceridine.

Anxiety disorders are common mental disorders often accompanied by varying degrees of dysfunction. However, its causes and related pathological mechanisms are still unclear. In recent years, many studies have found abnormalities in the cerebellar structure and function of patients with anxiety disorders, with significant heterogeneity observed among different subtypes of anxiety disorders. This article reviews the studies on cerebellar imaging features in patients with different subtypes of anxiety disorders, exploring potential research directions on the pathogenesis of anxiety disorders from both structural and functional perspectives.

Objective To investigate a reasonable threshold of total bilirubin for the diagnosis of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF), and to realize accurate early diagnosis. Methods A retrospective analysis was performed for the clinical data of 1232 patients with HBV-ACLF who were admitted to The Fifth Medical Center of Chinese PLA General Hospital from September 2008 to September 2018, and according to the baseline serum level of total bilirubin (TBil), the patients were divided into group A (TBil < 205.2 μmol/L) and group B (TBil ≥205.2 μmol/L). the two groups were compared in terms of clinical features and 28-day, 90-day, 1-year, and 3-year survival. The t -test or the Mann-Whitney U rank sum test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The Kaplan-Meier method was used to analyze survival rate, and the log-rank test was used for comparison. Results There were significant differences between the two groups in age( t =3.188, P =0.001) male sex( χ 2 =33.833, P < 0.001), liver failure classification( χ 2 =39.987, P < 0.001), white blood cell count( Z =6.586, P < 0.001), hemoglobin( Z =4.272, P < 0.001), platelet count( Z =3.680, P < 0.001), creatinine( Z =4.505, P < 0.001), total cholesterol( Z =8.644, P < 0.001), Na( Z =2.335, P =0.020), albumin( Z =2.592, P =0.010), HBV DNA( Z =3.703, P < 0.001), Model for End-Stage Liver Disease score( Z =11.828, P < 0.001), and MELD-Na score( Z =8.410, P < 0.001). At baseline, there were significant differences in the incidence rates of ascites and gastrointestinal bleeding between the two groups ( χ 2 =12.036、4.342, P < 0.05). Infection was the most common new-onset complication within 28 days, followed by hepatic encephalopathy, and there was a significant difference in the incidence rate of infection between the two groups ( χ 2 =5.294, P < 0.05). The 28-day transplant-free mortality rate was 21.2% in group A and 29.5% in group B( HR =1.473[95% CI : 1.151~1.886], P =0.005), which was consistent with the clinical feature of a high short-term mortality rate (> 15%) in patients with acute-on-chronic liver failure (ACLF). Although there was a difference in long-term mortality rate between the two groups, there was no significant increase in transplant-free mortality rate after 90 days in either group. Conclusion Under the premise of international normalized ratio ≥1.5, it is not recommended to increase the threshold of TBil to 205.2 μmol/L in the diagnostic criteria for HBV-ACLF, so as to ensure the early diagnosis of more ACLF patients and bring more opportunities for treatment and cure.

Objective:To investigate the clinical efficacy of proximal gastrectomy and total gastrectomy in the treatment of Siewert type Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction (AEG).Methods:The retrospective cohort study was conducted. The clinicopathological data of 170 patients with Siewert type Ⅱ and Ⅲ AEG who were admitted to Guangdong Provincial People′s Hospital from January 2010 to December 2018 were collected. There were 125 males and 45 females, aged from 30 to 85 years, with a median age of 64 years. Of the 170 patients, 82 cases undergoing proximal gastrectomy were allocated into the proximal gastrectomy group and 88 cases undergoing total gastrectomy were allocated into the total gastrectomy group. Observation indica-tors: (1) surgical and postoperative situations; (2) follow-up and survival; (3) analysis of prognostic factors. Follow-up was conducted using telephone interview and outpatient examination to detect survival of patients up to December 2021. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measure-ment data with skewed distribution were represented as M( Q1, Q3) or M(range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Comparison of ordinal data was analyzed using the rank sum test. Kaplan-Meier method was used to draw survival curves, and Log-Rank test was used for survival analysis. COX proportional hazard model was used for univariate and multivariate analyses. Variables with P<0.1 in univariate analysis were included for multivariate analysis. Results:(1) Surgical and postoperative situations. Cases with surgical approach as transthoracic or thoraco-abdominal approach, transabdominal approach, the operation time, cases with volume of intra-operative blood loss ≤100 mL or >100 mL, cases with length of proximal margin ≤1.5 cm or >1.5 cm, cases with radical surgery outcome as R 0, R 1, R 2, the number of lymph nodes harvest, cases with anastomotic leakage, cases with anastomotic stricture, cases with incision infection, cases with pleural infection or effusion, cases with abdominal infection or ascites were 61, 21, (211±18)minutes, 46, 36, 44, 38, 73, 6, 3, 15(9,22), 5, 2, 2, 4, 2 in the proximal gastrectomy group, respec-tively. The above indicators were 12, 76, (263±15)minutes, 27, 61, 45, 43, 82, 4, 2, 23(18,32), 4, 1, 3, 1, 4 in the total gastrectomy group, respectively. There were significant differences in the surgical approach, operation time, volume of intraoperative blood loss and the number of lymph nodes harvest between the two groups ( χ2=63.94, t=-25.50, χ2=11.19, Z=-5.62, P<0.05). There was no significant difference in the length of proximal margin or radical surgery outcome between the two groups ( χ2=0.11, Z=-0.95, P>0.05) and there was no significant difference in the anastomotic leakage, anastomotic stricture, incision infection, pleural infection or effusion, abdominal infection or ascites between the two groups ( P>0.05). (2) Follow-up and survival. All the 170 patients were followed up for 89(64,106)months. Of the 170 patients, the 5-year overall survival rates were 43.8% and 35.5% of the Siewert type Ⅱ and Ⅲ AEG patients, respectively, showing no significant difference between them ( χ2=0.87, P>0.05). Of the patients with Siewert type Ⅱ AEG, the 5-year overall survival rates were 41.7% and 54.3% in the patients with proximal gastrectomy and the total gastrectomy, respectively, showing no significant difference between them ( χ2=1.05, P>0.05). Of the patients with Siewert type Ⅲ AEG, the 5-year overall survival rates were 31.3% and 37.5% in the patients with proximal gastrectomy and the total gastrectomy, respectively, showing no significant difference between them ( χ2=0.33, P>0.05). The 5-year overall survival rates were 39.0% and 44.2% in the proximal gastrectomy group and the total gastrectomy group, respectively, showing no significant difference between the two groups ( χ2=0.63, P>0.05). Of the patients in TNM stage Ⅰ, stage Ⅱ, stage Ⅲ, the 5-year overall survival rates were 65.3%, 36.3%, 27.1% in the proximal gastrectomy group, versus 83.3%, 48.0%, 39.7% in the total gastrectomy group, showing no signifi-cant difference between the two groups ( χ2=0.02, 1.50, 1.21, P>0.05). (3) Analysis of prognostic factors. Results of univariate analysis showed that pathological N staging, degree of tumor differen-tiation and radical surgery outcome were related factors influencing prognosis of AEG patients ( hazard ratio=1.71, 1.70, 2.85, 95% confidence interval as 1.16-2.60, 1.15-2.50, 1.58-5.14, P<0.05). Results of multivariate analysis showed that pathological N staging and radical surgery outcome were independent factors influencing prognosis of AEG patients ( hazard ratio=1.55, 2.18, 95% confidence interval as 1.05-2.31, 1.18-4.02, P<0.05). Conclusions:There is no significant difference in the prognosis of Siewert type Ⅱ and Ⅲ AEG patients undergoing proximal gastrectomy or total gastrectomy. Proximal gastrectomy can be used for the treatment of advanced Siewert type Ⅱ and Ⅲ AEG.

Objective:To establish an analytical method for measuring the concentration of glucose in saliva by ion chromatography.Methods:The proteins in saliva were removed by thermal denaturation method, CarboPac PA20 (3×30 mm) was used as a protective column and CarboPac PA20 (3×150 mm) was used as an analytical column for ion chromatography analysis. Gradient elution was carried out with A: ultra-pure water, B: 250 mmol/L NaOH solution and C: 500 mmol/L NaAc solution. Pulsed ampere detector was used for detection.Results:This method had a good linear relationship in the range of 0.04 to 0.12 mg/L, with a linear relation coefficient of 0.9967. The detection limit of glucose was 2 μg/L, the mean value of the relative standard deviation (RSD) of the repeatability measurement was 0.75%, and the average spike recovery was 103.07%.Conclusion:This method is simple, sensitive, accurate and stable, and can be used for the determination of glucose concentration in saliva.