OBJECTIVE To explore whether pachymic acid （Pac） regulates mitochondrial autophagy mediated by the PTEN- induced kinase 1 （PINK1）/Parkin RBR E3 ubiquitin-protein ligase （Parkin） signaling pathway to alleviate myocardial injury in coronary heart disease （CHD） rats. METHODS SD rats were divided into control （Con） group， CHD group， Pac low-dose group （Pac-L group）， Pac high-dose group （Pac-H group）， Pac-H+PINK1/Parkin signaling pathway inhibitor group （Pac-H+3-MA group）， with 10 rats in each group. Except for the Con group， CHD models were established in the remaining groups of rats. After successful modeling， the rats in each group were intraperitoneally injected with the corresponding drugs or normal saline. After continuous intervention for 4 weeks， the left ventricular ejection fraction （LVEF）， left ventricular end-diastolic volume （LVEDV）， left ventricular end-systolic volume （LVESV）， and mean arterial pressure （MAP） of the rats were detected. The levels of creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， cardiac troponin I （cTnI）， and cardiac troponin T （cTnT） in the serum， as well as the levels of tumor necrosis factor-α （TNF-α）， interleukin-10 （IL-10）， IL-1β， reactive oxygen species （ROS）， malondialdehyde （MDA） in the myocardial tissue， and the activities of catalase （CAT） and superoxide dismutase （SOD）， as well as the expression levels of p62， cleaved caspase-3， Parkin， PINK1 proteins and the ratio of microtubule-associated protein 1 light chain 3 Ⅱ （LC3Ⅱ）/LC3Ⅰ ratio were measured. The morphology of myocardial tissue and mitochondrial autophagic vesicles were observed， and the number of mitochondrial autophagic vesicles per unit area and the rate of cardiomyocyte apoptosis were counted. RESULTS Compared with CHD group， LVEF， MAP， IL-10 levels， CAT and SOD activities， p62， Parkin， PINK1 protein expressions， LC3Ⅱ/LC3Ⅰ ratio， the numbers of mitochondrial autophagic vesicles per unit area in the Pac-L and Pac-H E-mail：hzdpft@163.com groups were increased significantly （P＜0.05）； the levels of LVEDV， LVESV， CK-MB， LDH， cTnI， cTnT， TNF-α， IL-1β， ROS and MDA， cell apoptosis rates， and protein expression of cleaved caspase-3 were all decreased significantly （P＜0.05）； and the changes in various indicators were more pronounced in the Pac-H group （P＜0.05）； both groups showed varying degree of improvement in myocardial histopathological morphology. Compared with the Pac-H group， the aforementioned indicators in rats from the Pac-H+3-MA group were all significantly reversed （P＜0.05）. CONCLUSIONS Pac may promote mitochondrial autophagy in cardiomyocytes of CHD rats by activating the PINK1/ Parkin signaling pathway， thereby reducing inflammatory responses and oxidative stress and improving myocardial injury.

BACKGROUND:The development of steroid-induced osteonecrosis of the femoral head is a complex process involving multiple mechanisms.There is still no standard therapeutic drug for early intervention of this disease.Current studies have shown that baicalein has various pharmacological activities such as regulating lipid metabolism,bone metabolism,apoptosis and anti-oxidative stress,which provides an idea for the prevention and treatment of steroid-induced osteonecrosis of the femoral head. OBJECTIVE:To observe the preventive effect of baicalein against steroid-induced osteonecrosis of the femoral head and to investigate its possible mechanism. METHODS:Thirty-six 10-week-old male Sprague-Dawley rats were randomly divided into three groups(n=12 per group):blank control group,model group,and baicalein intervention group.In the model group and baicalein intervention group,intraperitoneal lipopolysaccharide and intramuscular injection of methylprednisolone sodium succinate were performed for modeling,while normal saline was used as a substitute for the modeling drug in the blank control group.Baicalein 300 mg/kg was administered by gavage(once a day for 6 weeks)at the time of initial intramuscular glucocorticoid injection in the baicalein intervention group,and baicalein was replaced by normal saline in the other two groups.The serum level of malondialdehyde in rats was detected at 2 weeks of the experiment.Blood lipid indicators and bone formation metabolic markers were detected at 6 weeks of the experiment,the histomorphometric changes of the femoral head were analyzed by hematoxylin-eosin staining,anti-tartaric acid phosphatase staining and TUNEL staining,and the femoral head was subjected to Micro-CT scanning and three-dimensional reconstruction of the bone in order to analyze the alterations of bone tissue structure and parameters. RESULTS AND CONCLUSION:The serum levels of malondialdehyde,triglyceride,β-collagen type Ⅰ carboxy-terminal peptide were increased and the serum levels of bone specific alkaline phosphatase and pre-collagen type Ⅰ amino-terminal peptide were decreased in the model group compared with the blank control group(P＜0.05).The serum level of malondialdehyde decreased in the baicalein intervention group compared with the model group(P＜0.05),but there was no significant difference between the baicalein intervention group and blank control group(P＞0.05).The serum level of triglyceride was higher in the baicalein intervention group than the blank control group(P＜0.05),but had no significant difference between the baicalein intervention group and model group(P＞0.05).There were also no significant differences in the levels of bone specific alkaline phosphatase and β-collagen type Ⅰ carboxy-terminal peptide between the baicalein intervention group and the other two groups(P＞0.05).The serum level of the baicalein intervention group was lower in the baicalein intervention group than the blank control group(P＜0.05)but had no significant difference between the baicalein intervention group and model group(P＞0.05).Histomorphological analysis of the femoral head showed that the rate of bone empty lacuna,osteoclast counting and cell apoptosis rate in the femoral head of model group rats were significantly higher than those of the other two groups(P＜0.05).There was a significant increase in the number of adipocytes in the bone marrow cavity of the femoral head,bone trabeculae were thinned and sparsely arranged with more disruptions in the continuity.The incidence of osteonecrosis was higher in the model group(75%)than in the baicalein intervention group(25%;bilateral and unilateral exact significance results were both 0.05).There was also an increase in the number of adipocytes in the bone marrow cavity of the femoral head in the baicalein intervention group,and the trabecular changes were roughly similar to those in the model group.Micro-CT results showed that bone volume fraction,trabecular thickness,trabecular number,and bone mineral density decreased and trabecular separation increased in the model group compared with the blank control group(P＜0.05).Overall significant bone mass loss was observed in the model group.Bone tissue parameters in the baicalein intervention group were significantly improved than those in the model group,which were reflected in bone volume fraction,trabecular thickness and trabecular separation(P＜0.05),and trabecular number and bone mineral density had no significant difference between the baicalein intervention group and blank control group(P＞0.05).Although baicalein failed to significantly ameliorate dyslipidemia and promote bone formation in rats with steroid-induced osteonecrosis of the femoral head,it could reduce the incidence of steroid-induced osteonecrosis of the femoral head by reducing oxidative stress damage,decreasing cell apoptosis,inhibiting osteoclasts,suggesting its effectiveness in the early prevention of steroid-induced osteonecrosis of the femoral head.

Aural vertigo frequently encountered in the otolaryngology department of traditional Chinese medicine （TCM） mainly involves peripheral vestibular diseases of Western medicine， such as Meniere's disease， benign paroxysmal positional vertigo， vestibular neuritis， and vestibular migraine， being a hot research topic in both TCM and Western medicine. Western medical therapies alone have unsatisfactory effects on recurrent aural vertigo， aural vertigo affecting the quality of life， aural vertigo not relieved after surgery， aural vertigo with complex causes， and children's aural vertigo. The literature records and clinical practice have proven that TCM demonstrates unique advantages in the treatment of aural vertigo. The China Association of Chinese medicine sponsored the "17th youth salon on the diseases responding specifically to TCM： Aural vertigo" and invited vertigo experts of TCM and Western medicine to discuss the difficulties and advantages of TCM diagnosis and treatment of aural vertigo. The experts deeply discussed the achievements and contributions of TCM and Western medicine in the diagnosis and treatment of aural vertigo， the control and mitigation of the symptoms， and the solutions to disease recurrence. The discussion clarified the positioning and advantages of TCM treatment and provided guidance for clinical and basic research on aural vertigo.

Objective:To describe and analyze suicide risk of patients with schizophrenia,major depressive disorder,and bipolar disorder.Methods:A total of 2 016 patients with schizophrenia,903 patients with major de-pressive disorder,and 381 patients with bipolar disorder from inpatients,clinics,or communities who met the diag-nostic criteria of the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition were recruited.All patients were interviewed by psychiatrists using the Mini International Neuropsychiatric Interview to diagnose mental disor-ders and assess suicide risk,as well as Clinical-Rated Dimensions of Psychosis Symptom Severity(CRDPSS)to as-sess symptoms.Differences and risk factors of suicide risk among three types of mental disorders were explored u-sing multivariate logistic regression analysis.Results:In the past one month,37 patients with schizophrenia(1.8％),516 patients with major depressive disorder(57.1％),and 102 patients with bipolar disorder(26.8％)had suicide risk.Compared with patients with schizophrenia,suicide risk in patients with major depressive disorder(OR=36.50)and bipolar disorder(OR=20.10)increased.Female(OR=1.87),smoking(OR=1.76),family history of suicide(OR=5.09),higher score of CRDPSS hallucination(OR=1.80),and higher score of CRDPSS depression(OR=1.54)were risk factors of suicide risk of patients.Conclusions:Suicide risk of patients with ma-jor depressive disorder and bipolar disorder is higher than that of patients with schizophrenia.In clinical practice,it is important to regularly assess suicide risk of patients.Patients who experience symptoms of hallucination and de-pression should be paid more attention to.

Objective:To explore the clinical characteristics and related socio-demographic factors of schizo-phrenia patients with different ages of onset.Methods:Totally 2 016 patients with schizophrenia aged 15 to 70 were selected according to the diagnostic criteria for schizophrenia in the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition.All of the patients were interviewed by psychiatrists using the Mini International Neuropsy-chiatric Interview to diagnose schizophrenia,Clinical-Rated Dimensions of Psychosis Symptom Severity(CRDPSS)and the Positive and Negative Syndrome Scale(PANSS)to assess symptoms.The cut-off points were 18 and 25 years old for three age groups,i.e.early onset(EOS),youth onset(YOS)and adult onset(AOS).Statistical analy-ses were performed by analysis of variance Pearson correlation analysis,and multivariate linear regression.Results:The early-onset patients had the highest total PANSS score(73.8±28.0)and CRDPSS score(11.7±5.4).Fe-male gender,high education level,Han ethnicity,early onset age,and slower onset of illness were negatively corre-lated with the total and dimension score of PANSS scale and CRDPSS scale(standardized regression coefficient:0.04-0.47),and income level and smoking were negatively correlated with those score(standardized regression coefficient:-0.04--0.14).Conclusion:Early-onset schizophrenia patients have more severe symptoms,and fe-male,high education level,early-onset disease,and chronic onset are the risk factors of symptom severity in patients with schizophrenia.

In order to establish the isolation,culture and identification method of cow bone marrow-derived macrophages,three different media(RPMI-1640,DMEM,DMEM/F12)were added with 20％fetal bovine serum(FBS),2.4％chlorine-streptomycin,1.2％glutamine(Gln),and M-CSF(20 ng/mL),respectively,to induce the monocytes extracted from the bone marrow of dairy cows to become macrophages.The induced M0 macrophages were polarized into M1-type macrophages by adding lipopolysaccharide(LPS).The morphology of macrophages was observed by optical mi-croscope at day 1,4 and 7,and the differences of differentiated macrophages between the three media were compared.The effects of prostaglandin D2(PGD2)-DP2 receptor pathway on the secre-tion of cytokines(IL-6,TNF-α)induced by Escherichia coli and phagocytosis of macrophages were also investigated.The results showed that the morphological changes of cells cultured in the medium of RPMI-1640 were the most obvious and the number was large.A large number of char-acteristic markers of mononuclear macrophages were detected(M0 markers:CD1 1b,CD14;M1 markers:CD11b,CD80)expression,M0 and M1 macrophage purity were 79.9％and 93.5％,re-spectively.COX-2 and H-PGDS gene expressions were significantly increased in E.coli group com-pared with the blank control group.The secretion of PGD2also increased significantly(P＜0.000 1).DP2 receptor inhibitors(CAY10471,CAY10595)could significantly inhibit the secretion of E.coli in-duced pro-inflammatory cytokines(IL-6,TNF-α)and significantly enhance the killing effect of macrophages on E.coli.The above results showed that the induced cells had the characteristic mor-phology and immunophenotype of macrophages.E.coli can induce the production of PGD2 in mac-rophages,and the PGD2-DP2 pathway regulates the secretion of cytokines in E.coli infected macro-phages.

Aim To explore the improvement effect of Bazi Bushen capsule on thymic degeneration in SAMP6 mice and the possible mechanism.Methods Twenty 12 week old male SAMP6 mice were randomly divided into the model group(SAMP6)and the Bazi Busheng capsule treatment group(SAMP6+BZBS).Ten SAMR1 mice were assigned to a homologous control group(SAMR1).The SAMP6+BZBS group was oral-ly administered Bazi Bushen capsule suspension(2.8 g·kg-1)daily,while the other two groups were orally administered an equal amount of distilled water.After nine weeks of administration,the morphology of the thymus in each group was observed and the thymus in-dex was calculated;HE staining was used to observe the structural changes of thymus tissue;SA-β-gal stai-ning was used to detect thymic aging;flow cytometry was used to detect the proportion of thymic CD3+T cells in each group;Western blot was used to detect the levels of p16,Bax,Bcl-2,and cleaved caspase-3 proteins in thymus;immunofluorescence was applied to detect the proportion of cortical thymic epithelial cells in each group;ELISA was employed to detect IL-7 lev-els in thymus.Results Compared with the SAMP6 group,the thymic index of the SAMP6+BZBS group significantly increased(P＜0.05);the disordered thy-mic structure was significantly improved;the positive proportion of SA-β-gal staining significantly decreased(P＜0.01);the proportion of CD3+T cells apparently increased(P＜0.05);the level of p16 protein signifi-cantly decreased(P＜0.05);the level of Bcl-2 pro-tein significantly increased(P＜0.05),while the lev-el of cleaved caspase-3 protein markedly decreased(P＜0.05);the proportion of cortical thymic epithelial cells evidently increased;the level of IL-7 significantly increased(P＜0.01).Conclusions Bazi Bushen capsule can delay thymic degeneration,inhibit cell ap-optosis in thymus and promote thymic cell development in SAMP6 mice,which may be related to increasing the proportion of cortical thymic epithelial cells and promoting IL-7 secretion.

In order to improve the poor photostability of nifedipine, this study designed a cocrystal based on the principles of crystal engineering and prepared nifedipine-imidazole cocrystal by suspension method. The new cocrystal was characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TG) and infrared spectroscopy (IR) to confirm the formation of the cocrystal. The photostability of nifedipine and its cocrystal was measured by powder X-ray diffraction and high-performance liquid chromatography (HPLC). The results showed that the nifedipine-imidazole cocrystal improved the photostability of nifedipine to a certain extent. This study provides guidance for the development of nifedipine cocrystals and the improvement of its druggability.

BACKGROUND/OBJECTIVES: The study examined the association between homocysteine and diabetes mellitus in patients with H-type hypertension and assessed the possible effect modifiers. SUBJECTS/METHODS: This cross-sectional study included 1,255 eligible participants in the ‘H-type Hypertension Management and Stroke Prevention Strategic International Science and Technology Innovation Cooperation Project’ among rural Chinese people with H-type hypertension. A multivariate logistic regression model was used to evaluate the relationship between homocysteine and diabetes mellitus. RESULTS: The mean level of total homocysteine (tHcy) in the diabetes mellitus population was 19.37 μmol/L, which was significantly higher than the non-diabetic patients (18.18 μmol/L). When tHcy was analyzed as a continuous variable, the odds ratio (OR) of diabetes was 1.17 (95% confidence interval [CI], 1.01–1.35; per interquartile range). When tHcy was stratified according to the quintile, the ORs for diabetes were 2.86 (95% CI, 1.22–6.69) in the highest quintile (tHcy ≥ 20.60 μmol/L) compared to the reference group (tHcy < 12.04 μmol/L). When tHcy was grouped by 15 μmol/L and 20 μmol/L, patients with tHcy ≥ 20 μmol/L had a significantly (P = 0.037) higher risk of diabetes (OR, 2.03; 95% CI, 1.04–3.96) than in those with tHcy < 15 μmol/L. Subgroup analysis showed that the tHcy-diabetes association was unaffected by other variables. CONCLUSION In this study of rural Chinese people with H-type hypertension, the tHcy levels showed a positive association with diabetes mellitus. This independent association is unaffected by other potential risk factors.

OBJECTIVE: Clinical characteristics and outcome in COVID-19 with brucellosis patients has not been well demonstrated, we tried to analyze clinical outcome in local and literature COVID-19 cases with brucellosis before and after recovery. METHODS: We retrospectively collected hospitalization data of comorbid patients and prospectively followed up after discharge in Heilongjiang Infectious Disease Hospital from January 15, 2020 to April 29, 2022. Demographics, epidemiological, clinical symptoms, radiological and laboratory data, treatment medicines and outcomes, and follow up were analyzed, and findings of a systematic review were demonstrated. RESULTS: A total of four COVID-19 with brucellosis patients were included. One patient had active brucellosis before covid and 3 patients had nonactive brucellosis before brucellosis. The median age was 54.5 years, and all were males (100.0%). Two cases (50.0%) were moderate, and one was mild and asymptomatic, respectively. Three cases (75.0%) had at least one comorbidity (brucellosis excluded). All 4 patients were found in COVID-19 nucleic acid screening. Case C and D had only headache and fever on admission, respectively. Four cases were treated with Traditional Chinese medicine, western medicines for three cases, no adverse reaction occurred during hospitalization. All patients were cured and discharged. Moreover, one case (25.0%) had still active brucellosis without re-positive COVID-19, and other three cases (75.0%) have no symptoms of discomfort except one case fell fatigue and anxious during the follow-up period after recovery. Conducting the literature review, two similar cases have been reported in two case reports, and were both recovered, whereas, no data of follow up after recovery. CONCLUSION These cases indicate that COVID-19 patients with brucellosis had favorable outcome before and after recovery. More clinical studies should be conducted to confirm our findings.
Female ; Humans ; Male ; Middle Aged ; Brucellosis ; COVID-19 ; Retrospective Studies ; SARS-CoV-2 ; Treatment Outcome ; Case Reports as Topic