Mechanism of Yi-xin-yin oral liquid according to homotherapy for heteropathy theory based on UHPLC-Q-TOF/MS combined with network pharmacology and molecular docking techniques / 中国临床药理学与治疗学

AIM: To predict the core targets and related signaling pathways of Yi-xin-yin oral liquid for the treatment of arrhythmia, heart failure and myocarditis based on UHPLC-Q-TOF/MS, network pharmacology, molecular docking methods, cell experiments, according to the“homotherapy for heteropathy”theory in traditional Chinese medicine. METHODS: UHPLC-Q-TOF / MS was used to analyze and identify the chemical composition of Yi-xin-yin oral liquid Extract and the blood-absorbing components of rats oral administrated with Yi-xin-yin oral liquid extract, which compounds were applied in the databases searching for the potential targets (TCMSP, SwissTargetPrediction) and disease targets (OMIM, Genecard). Venn diagram was used for target intersection, and the subsequent protein-protein interaction network obtained core targets by STRING11.5 database, and then construct a "disease-component-target" network by cytoscape3.9.0. Finally, DAVID database was used to analysis GO function and KEGG enrichment analysis of core targets, and molecular docking validation was performed using Autodock vina software. And, validated with H9c2 cells for potential active ingredients and targets. RESULTS: A total of 156 compounds were identified from Yi - xin-yin Oral Liquid extract; 34 compounds were identified from rat serum, including 6-gin-gerol, isoliquiritigenin, glycyrrhizic acid and other compounds, and 139 intersecting targets were obtained. The KEGG pathway enrichment analysis mainly involved the TNF signaling pathway, IL-17 signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway and so on. The TNF and IL-6 targets were selected for molecular docking with the main compounds, and the docking results were good (less than -5 kcal/mol). In vitro cellular experiments have shown that Yi-xin-yin oral liquid can exert therapeutic effects by regulating TNF and IL-6. CONCLUSION: The main potential active ingredients of Yi-xin-yin oral liquid may be isoliquiritigenin, glycyrrhetinic acid, calycosin-7-glucoside, salvianolic acid B, and 6-gingerol, which mainly act on TNF, IL-6 and other targets to regulate specific signaling pathways and exert therapeutic effects.

Limonin inhibits apoptosis, promotes autophagy and improves non-alcoholic fatty liver disease by promoting oxidative metabolism of fatty acids through PPARα / 药学学报

Non-alcoholic fatty liver disease (NAFLD) is a very common chronic liver disease in clinic, which can further develop into liver fibrosis, cirrhosis, eventually hepatocellular carcinoma and liver failure. Limonin is a natural triterpenoid compound containing furan rings. Previous studies have found that limonin has good anti-inflammatory, analgesic and liver protective functions. However, the mechanism of action of limonin on NAFLD has not been clarified. Based on the background, C57BL/6J male mice were fed with high fat diet (HFD) to establish NAFLD model (the experiment was approved by the Animal Ethics Committee of Hefei University of Technology, the approval number is HFUT20220429001), and limonin was added to the mice for administration by intragastric administration (i.g.). The results showed that HFD can induce typical NAFLD phenotypes, including impaired liver function, increased fat accumulation, and increased serum aspartate amino transferase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) levels in mice. Mice were treated with limonin (50 and 100 mg·kg-1) for 10 weeks, and it was found that limonin could restore dyslipidemia and improve fat accumulation in liver cells of mice. In addition, we conducted in vitro experiments with human hepatoma cell line HepG2 cells, and found that limonin can promote the expression of oxidative metabolism and autophagy related genes and inhibit apoptosis in HepG2 cells. Mechanistically, limonin improves high-fat food-induced NAFLD by promoting the expression of oxidative metabolism genes transcriptional coactivator of peroxisome proliferator activating receptor γ (PPARγ) (PGC1α) and carnitine palmitoyl transferase 1 alpha (CPT1α) through peroxisome proliferator activates receptor alpha (PPARα). These results indicate that limonin can inhibit apoptosis, promote autophagy and improve NAFLD by promoting oxidative metabolism of fatty acids through PPARα.

Comparative study on the methods to determine disintegration time of oral soluble films / 药学学报

Disintegration time is a key parameter that affects the palatability and compliance of oral soluble films. At present, there is no standard method to determine the disintegration time of oral soluble films. In this study, we compared the six methods (pharmacopoeial disintegration method, petri dish method, sponge surface method, slide frame and ball method, partially immersed into liquid (without weight attached) and partially immersed into liquid (with weight attached)) to determine the in vitro disintegration time of oral soluble films with different thickness, and evaluated the correlation with the in vivo disintegration time. The results showed that the repeatability and correlation of pharmacopoeial disintegration method and the partially immersed into liquid method (with weight attached) were excellent, with the endpoint of disintegration testing easy to determine. Partially immersed into liquid method (with weight attached), properly simulating the physiological condition in oral cavity, showed strong operability, good repeatability and in vitro-in vivo correlation, and was suitable for in vitro disintegration evaluation of oral soluble film dosage form. The adult sensory evaluation study was a research-based clinical trial conducted with informed consent from all subjects in accordance with the ethical requirements of Good Clinical Practice.

Formulation optimization and analysis of taste-masking effect of licorzine granules based on sensory evaluation and electronic tongue method / 药学学报

Licorzine granules are common preparations for children zinc deficiency. Considering the long course of treatment, the taste of licorzine granules may become a main factor affecting medication adherence. To date there have been no taste evaluation research into licorzine granules yet. In this study, both sensory evaluation and electronic tongue method were utilized to optimize licorzine granules formulations, evaluate the tastes of licorzine, excipients, optimized formulation in vivo and in vitro. As the results show, bitterness and astringency are the main unpleasant tastes generating from licorzine. Xanthan gum is the main taste-masking excipient, lowering down the bitterness and astringency of licorzine by at least one grade. Good correlation exists between the results of sensory evaluation and electronic tongue method, and an integrated combination of the two helps to obtain objective and rational research conclusions. The adult sensory evaluation study was a research-based clinical trial conducted with informed consent from all subjects in accordance with the ethical requirements of Good Clinical Practice.

Follow-up and retrospective investigation of pneumoconiosis cases in a county of Ningbo City from 1974 to 2019 / 环境与职业医学

Background Pneumoconiosis is one of the most common and widespread prescribed occupational diseases in China, and there is no cure for it at present. The Healthy China 2030 underlines that the prevention and treatment of pneumoconiosis are the critical element of promoting occupational health. Objective To understand the basic characteristics, social security, and death causes of pneumoconiosis cases in Ninghai County, and to provide a basis for scientific prevention and treatment of pneumoconiosis. Methods Information on pneumoconiosis cases in Ninghai County from 1974 to 2019 was obtained by consulting occupational disease and occupational health information monitoring systems, occupational disease diagnosis institutions, and employers, which may retain original data on occupational pneumoconiosis diagnosis, as well as specialized epidemiological survey projects on pneumoconiosis. Telephone or face-to-face follow-up visits were conducted based on relevant information to complete or verify relevant information such as length of service with dust exposure, type, stage, and diagnosis date of pneumoconiosis. ANOVA, chi-square test, and rank-sum test were used to analyze age of diagnosis and age of death, entitlement to social security and mortality rate of cases/length of service. Results As of the end of 2019, a total of 420 cases of pneumoconiosis were diagnosed among workers exposed to dust in Ninghai County, with 409 cases (97.38%) followed up and 11 cases (2.62%) lost to follow-up. Since the first case of pneumoconiosis was reported in 1974, 39 cases, 278 cases, and 101 cases of pneumoconiosis were reported before 2000, from 2000 to 2009, and from 2010 to 2019, respectively. Two other cases of pneumoconiosis were diagnosed with an unknown year, one as a dead case and one as a lost case. There were 294 surviving pneumoconiosis cases, who mainly lived in Sangzhou Town. The mean age of diagnosis was (58.68±15.37) years old, and the median length of service with exposure to dust was 8.0 (4.0, 15.7) years. The age of diagnosing stage III pneumoconiosis was less than that of stage I and stage II, and the difference between the age of diagnosing stage III and stage II pneumoconiosis was significant (P <0.05). There were 231 cases (78.57%) aged ≥ 60 years, while there were 74 cases aged ≥ 80 years (25.17%). There were 160 cases (54.42%) whose length of service was < 10 years. There were 12.59% and 7.82% of the total cases compensated by work injury insurance and civil compensation by employers, respectively. From the perspective of diagnosis period, the proportion of patients who collected work-related injury insurance and civil compensation from employers in the 2010—2019 year group was higher than that in the <2000 year group or the 2000—2009 year group (P<0.01). There were 115 fatal pneumoconiosis cases, and the fatality rates of stage I, II , and III pneumoconiosis were 23.86%, 18.18%, and 50.75%, respectively. The fatality rate of stage III pneumoconiosis was higher than that of stage I or II (P <0.05). The age of diagnosis and age of death of stage III pneumoconiosis cases were lower than those of stage I and II (P <0.05). The cause of death was definite in 65 patients, including 25 cases (38.46%) of respiratory diseases (except lung cancer) and 28 cases (43.07%) of tumors, and lung cancer accounted for 1/2 of the pneumoconiosis cases that died due to tumors. Conclusion The surviving pneumoconiosis cases in Ninghai are mainly older than 60 years old and largely live in Sangzhou Town. Constructing local rehabilitation stations should be taken as an opportunity to actively prevent and treat pneumoconiosis complications, further improving the quality of life of pneumoconiosis patients.

Application of Familial Y-STR Haplotype Mismatch Tolerance in Genealogy Inference / 法医学杂志

OBJECTIVES@#To provide a guideline for genealogy inference and family lineage investigation through a study of the mismatch tolerance distribution of Y-STR loci in Chinese Han male lineage.@*METHODS@#Three Han lineages with clear genetic relationships were selected. YFiler Platinum PCR amplification Kit was used to obtain the typing data of 35 Y-STR loci in male samples. The variation of Y-STR haplotypes in generation inheritance and the mismatch tolerance at 1-7 kinship levels were statistically analyzed.@*RESULTS@#Mutations in Y-STR were family-specific with different mutation loci and numbers of mutation in different lineages. Among all the mutations, 66.03% were observed on rapidly and fast mutating loci. At 1-7 kinship levels, the number of mismatch tolerance ranged from 0 to 5 on all 35 Y-STR loci, with a maximum step size of 6. On medium and slow mutant loci, the number of mismatch tolerance ranged from 0 to 2, with a maximum step size of 3; on rapidly and fast mutant loci, the number of mismatch tolerance ranged from 0 to 3, with a maximum step size of 6.@*CONCLUSIONS@#Combined use of SNP genealogy inference and Y-STR lineage investigation, both 0 and multiple mismatch tolerance need to be considered. Family lineage with 0-3 mismatch tolerance on all 35 Y-STR loci and 0-1 mismatch tolerance on medium and slow loci can be prioritized for screening. When the number of mismatch tolerance is eligible, family lineages with long steps should be carefully excluded. Meanwhile, adding fast mutant loci should also be handled with caution.

Short term follow-up of unstable femoral neck fractures in young adults treated with femoral neck system and cannulated compression screws / 中国骨伤

OBJECTIVE@#To investigate the clinical efficacy of femoral neck system(FNS) and three cannulated compression screws(CCS) in the treatment of unstable femoral neck fractures in young adults.@*METHODS@#The clinical data of 52 young and middle-aged patients with unstable femoral neck fractures admitted from August 2018 to August 2021 were reviewed and analyzed. All patients were divided into two groups according to the internal fixation method, 25 cases were treated with FNS fixation, 27 cases were treated with closed reduction and 3 CCS inverted triangular distribution. The operation time, incision length, intraoperative bleeding, hospitalization expenses and fracture reduction quality of two groups were recorded and compared;The patients were followed up regularly after operation. The fracture healing time, complete weight-bearing time and postoperative complications(nonunion, femoral neck shortening, femoral head necrosis) of two groups were compared. The Harris score was used to evaluate hip function 6 months after surgery.@*RESULTS@#The operation was successfully completed in both groups. The patients in FNS group had more bleeding, longer incision length and higher hospitalization cost than CCS group(P<0.01). There ware no significant difference in operation time and Garden index between two groups(P>0.05). Patients in both groups were followed up for 6 to 32 months.The fracture healing time in FNS group was less than that in CCS group, the time of complete weight bearing after surgery was earlier than that in CCS group, and the hip Harris score was higher than that in CCS group (P<0.01). There were no internal fixation fracture complications in two groups during follow-up. In the FNS group, there were 4 cases of avascular necrosis of the femoral head and 2 cases of femoral neck shortening, of which 3 cases underwent total hip replacement due to avascular necrosis of the femoral head. In the CCS group, there were 2 cases of nonunion, 9 cases of avascular necrosis of the femoral head, and 11 cases of femoral neck shortening, among which 5 cases underwent total hip replacement due to nonunion and avascular necrosis of the femoral head.@*CONCLUSION@#With simple operation, rotational stability and angular stability, FNS enables patients to start functional exercise as early as possible and reduces the incidence of postoperative complications of unstable femoral neck fracture. It is a new choice for the treatment of unstable femoral neck fracture in young adults.

Angiotensin-(1-7) improves endothelium-dependent vasodilation in rats with monocrotaline-induced pulmonary arterial hypertension / 生理学报

In this study, we used a rat model of pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT) to investigate the role and mechanism of angiotensin (Ang)-(1-7) in regulating pulmonary artery diastolic function. Three weeks after subcutaneous injection of MCT or normal saline, the right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI) of rats were detected using a right heart catheter. Vascular endothelium-dependent relaxation was evaluated by acetylcholine (ACh)-induced vasodilation. The relaxation function of vascular smooth muscle was evaluated by sodium nitroprusside (SNP)-induced vasodilation. Human pulmonary artery endothelial cells (HPAECs) were incubated with Ang-(1-7) to measure nitric oxide (NO) release levels. The results showed that compared with control rats, RVSP and RVHI were significantly increased in the MCT-PAH rats, and both ACh or SNP-induced vasodilation were worsened. Incubation of pulmonary artery of MCT-PAH rats with Ang-(1-7) (1 × 10-9-1 × 10-4 mol/L) caused significant vaso-relaxation. Pre-incubation of Ang-(1-7) in the pulmonary artery of MCT-PAH rats significantly improved ACh-induced endothelium-dependent relaxation, but had no significant effect on SNP-induced endothelium-independent relaxation. In addition, Ang-(1-7) treatment significantly increased NO levels in HPAECs. The Mas receptor antagonist A-779 inhibited the effects of Ang-(1-7) on endothelium-dependent relaxation and NO release from endothelial cells. The above results demonstrate that Ang-(1-7) promotes the release of NO from endothelial cells by activating Mas receptor, thereby improving the endothelium-dependent relaxation function of PAH pulmonary arteries.

Research on the establishment of standard limits for perfluorooctanoic acid and perfluorooctane sulfonate in the "Standards for Drinking Water Quality（GB5749-2022）"in China / 中华预防医学杂志

Perfluorinated compounds, especially Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), are widely detected in water environments in China. Considering the potential health risks of drinking water exposure routes, PFOA and PFOS have been added to the water quality reference index of the newly issued "Standards for Drinking Water Quality (GB5749-2022)", with limit values of 40 and 80 ng/L, respectively. This study analyzed and discussed the relevant technical contents for determining the limits of the hygiene standard, including the environmental existence level and exposure status of PFOA and PFOS, health effects, derivation of safety reference values, and determination of hygiene standard limits. It also proposed prospects for the future direction of formulating drinking water standards.

Identification of Human Body Fluid Stains and Non-Biological Stains by Three-Dimensional Fluorescence Spectroscopy / 法医学杂志

OBJECTIVES@#To establish a rapid and nondestructive identification method for human body fluid stains and non-biological stains using three-dimensional fluorescence spectroscopy.@*METHODS@#The collected three-dimensional fluorescence spectrum data of human saliva, 3% blood, coffee and Fanta® stains were processed with dimensionality reduction. After wavelet transform, spectral denoising and feature extraction, the classification formula was established. The Fisher discriminant was used for spectrum matching and recognition to establish the analysis method to distinguish stain types.@*RESULTS@#According to the results of data training and comparison, all the recognition accuracies of Fanta®, coffee, saliva and blood were more than 91.39%. Among them, saliva reached 100% recognition accuracy.@*CONCLUSIONS@#Three-dimensional fluorescence spectroscopy is a potential method for rapid and nondestructive identification of biological and non-biological stains.

Clinical characteristics and treatment of patients with acute acquired concomitant esotropia in different refractive status / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To analyze the clinical characteristics and treatment of patients with acute acquired concomitant esotropia(AACE)in different refractive status.METHODS: A retrospective analysis was conducted on 110 patients with non-type I AACE treated from January 2020 to January 2022. The non-myopic group(30 cases, spherical equivalent&#x003E;-0.5D)and the myopic group(80 cases, spherical equivalent≤-0.5D)were divided according to the refractive status. The degree of deviation, accommodative convergence and accommodation ratio(AC/A), visual function, and surgical methods were observed. RESULTS: The non-myopic group had no difference in the degree of near deviation [(47.13±23.54)△] and the degree of distant deviation [(48.90±22.59)△](P&#x003E;0.05); near deviation [(40.49±26.09)△] of myopic group was less than distant deviation [(50.09±25.41)△](P&#x003C;0.001); and there was no difference in the same distance between the two groups(P&#x003E;0.05). AC/A in the non-myopic group(5.40±2.23)was higher than that in the myopic group(3.14±3.10; P&#x003C;0.05). Patients in the myopic group had better near stereopsis than the non-myopic group(P&#x003C;0.05). The non-myopic group had a variety of surgical methods, while the myopic group mostly used lateral rectus resection or/and medial rectus recession.CONCLUSION: AACE can occur in different refractive status. Non-myopic patients have the same degree of distant and near strabismus, high AC/A, and varied surgical methods. However, myopic patients have less degree of near deviation than distant deviation and have normal AC/A and better near stereopsis, and lateral rectus resection or/and medial rectus recession are commonly used.

Value of generalized equivalent uniform dose optimization in radiotherapy for chest malignant tumors / 中国辐射卫生

Objective To explore the value of generalized equivalent uniform dose (gEUD) optimization in radiotherapy for chest malignant tumors. Methods Sixty patients with chest malignant tumors who were treated in Center for Tumor Radiotherapy, Chizhou Municipal People’s Hospital, Anhui Province, China from October 2021 to June 2022 were enrolled; each patient underwent tumor localization with a conventional fixed computed tomography scan. The patients were divided into two groups using the same field direction and weight in the Varian Eclipse 15.6 planning system. The first group was planned using the conventional physical dose-volume objective function plus the Upper gEUD objective function, with organs at risks (OARs) optimized with the EUD values suggested by the Varian Eclipse 15.6 planning system. The second group only adopted the conventional physical dose-volume objective function for OARs optimization. The two groups were compared for the radiation doses delivered to the OARs. Results Compared with the conventional physical dose-volume objective function alone, the addition of Upper gEUD objective function resulted in no significant difference in lung V5Gy, but resulted in significant reductions in V20Gy and mean dose in the lungs; some reductions in V30Gy, V40Gy, and mean dose in the heart; and significant reductions in the maximum dose in the spinal cord. Conclusion The gEUD objective optimization can effectively protect the normal tissue in the radiotherapy for chest malignant tumors and thus is recommended in radiotherapy planning.

The impact of image quality on the diagnostic performance of CT-derived fractional flow reserve / 中华放射学杂志

Objective:To explore the impact of coronary CT angiography (CCTA) image quality and related factors on the diagnostic performance of CT-derived fractional flow reserve (CT-FFR).Methods:Based on the CT-FFR CHINA trial, the prospective multicenter trial enrolled patients with suspected coronary artery disease who underwent CCTA, CT-FFR and FFR measurement. The subjective and objective assessments of CCTA image were performed on a per-vessel level. The objective assessments included the enhancement degree of coronary artery, the signal-to-noise ratio (SNR) of the aortic root. We used χ 2 test and DeLong test to compare the diagnostic performance of CT-FFR with FFR as the reference standard in different subjective groups (non-artifact vs. artifact), enhancement degree of coronary artery groups (≤400 vs. 401-500 vs.>500 HU), SNR of the aortic root groups (≤16.9 vs.>16.9), body mass index (BMI) groups (<25 kg/m 2 vs.≥25 kg/m 2) and heart rate groups (<75 bpm vs.≥75 bpm). FFR and CT-FFR values≤0.80 was identified as myocardial ischemia. Results:The study enrolled 317 patients with 366 vessels. All target vessels in CCTA images were successfully analyzed by CT-FFR. The accuracy, sensitivity, specificity, positive predictive value, negative predictive value and AUC of the non-artifact group were 90.45%, 86.75%, 93.10%, 90.00%, 90.76% and 0.928, respectively, and those of the artifact group were 83.23%, 87.21%, 79.01%, 81.52%, 85.33% and 0.869, respectively. The differences in accuracy and specificity were statistically significant (χ 2=4.23, P=0.040; χ 2=8.55, P=0.003). The diagnostic efficacy of CT-FFR had no statistically significant differences among different objective groups (all P>0.05). Conclusions:The artifact of CCTA image has an effect on CT-FFR in the diagnosis of myocardial ischemia. The degree of vascular enhancement, SNR, BMI, and heart rate have no significant effect on the diagnostic performance of CT-FFR.

Comparison of efficacy of modified single-incision and traditional double-incision for flexor hallucis longus tendon transfer in the treatment of Myerson type III chronic Achilles tendon ruptures in the middle-aged and elderly patients / 中华创伤杂志

Objective:To compare the efficacy of modified single-incision and traditional double-incision for flexor hallucis longus tendon transfer in the treatment of Myerson type III chronic Achilles tendon ruptures in the middle-aged and elderly patients.Methods:A retrospective cohort study was conducted to analyze the clinical data of 106 patients with Myerson type III chronic Achilles tendon ruptures admitted to Ningbo No.6 Hospital from January 2015 to May 2021, including 54 males and 52 females; aged 48-82 years [(67.2±8.4)years]. Flexor hallucis longus tendon transfer was assigned to 60 patients using modified single-incision (modified single-incision group) and to 46 patients using traditional double-incision (traditional double-incision group). The operation time, intraoperative blood loss as well as American foot and ankle society (AOFAS) ankle-hindfoot score, foot and ankle outcome score (FAOS), visual analogue score (VAS) before operation, at postoperative 12 months and at the last follow-up were compared between the two groups. Time to recover walking and self-care ability, and incidence of complications were compared as well.Results:All patients were followed up for 16-52 months [(37.4±9.5)months]. The operation time and intraoperative blood loss were (51.6±7.4)minutes and (16.6±3.9)ml in modified single-incision group compared to (72.8±7.5)minutes and (32.9±5.2)ml in traditional double-incision group (all P<0.01). There was no significant difference in the AOFAS ankle-hindfoot score, FAOS and VAS between the two groups before operation (all P>0.05). At postoperative 12 months and at the last follow-up, AOFAS ankle-hindfoot score and VAS were not significantly different between the two groups (all P>0.05), but FAOS in modified single-incision group [(112.6±3.0)points, (114.4±3.1)points] was improved significantly compared with traditional double-incision group [(110.8±4.1)points, (112.7±4.3)points] ( P<0.05 or 0.01). At postoperative 12 months and at the last follow-up, the AOFAS ankle-hindfoot score, FAOS and VAS in both groups were improved or decreased significantly compared with those before operation (all P<0.05). All patients recovered their pre-injury daily activities. The time to recover walking and self-care ability were (9.6±2.0)weeks and (12.7±1.7)weeks in modified single-incision group compared to (10.8±1.8)weeks and (13.7±1.9)weeks in traditional double-incision group (all P<0.01). In modified single-incision group, superficial incision infection ( n=1) was found and cured after oral antibiotics. In traditional double-incision group, superficial incision infection ( n=2), deep incision infection ( n=1), deep venous thrombosis ( n=1) and medial plantar nerve injury ( n=1) were found and cured after symptomatic internal medical therapy; claw toe deformity ( n=2) was found and relieved after wearing customized insoles and functional exercise. The incidence of complications was 1.7% (1/60) in modified single-incision group compared to 15.2% (7/46) in traditional double-incision group ( P<0.01). Conclusion:In contrast with traditional double-incision surgery, modified single-incision for flexor longus tendon transfer in the treatment of Myerson type III chronic Achilles tendon ruptures in the middle-aged and elderly patients has advantages such as shorter operation time, less intraoperative blood loss, better functional recovery, faster postoperative recovery and less complications.

Synergistic effects of lipopolysaccharide and rote-none on dopamine neuronal damage in rats / 中国药理学与毒理学杂志

OBJECTIVE The etiology of Parkinson disease(PD)is still unknown.Until now,oxidative stress and neuroinflammation play a crucial role in the patho-genesis of PD.However,the specific synergistic role of oxidative stress and neuroinflammation in the occurrence and development of PD remains unclear.METHODS The changes in motor behavior,dopamine(DA)neurons quantification and their mitochondrial respiratory chain,glial cells activation and secreted cytokines,Nrf2 signal-ing pathway,and redox balance in the brain of rats were evaluated.RESULTS Lipopolysaccharide(LPS)-induced neuroinflammation and rotenone(ROT)-induced oxidative stress synergistically aggravated motor dysfunc-tion,DA neuron damage,activation of glial cells,and release of related mediators,activation of Nrf2 signaling and destruction of oxidative balance.In addition,further studies indicated that after ROT-induced oxidative stress caused direct damage to DA neurons,LPS-induced inflammatory effects had stronger promoting neurotoxic effects on the above aspects.CONCLUSION Neuroinflammation and oxidative stress synergistically aggravated DA neuronal loss.Furtherly,oxidative stress followed by neuroinflammation caused more DA neuro-nal loss than neuroinflammation followed by oxidative stress.

Heat-killed Lactobacillus murinus confers neuropro-tection against dopamine neuronal loss by targeting NLRP3 inflammasome / 中国药理学与毒理学杂志

OBJECTIVE In this study,the effects of live Lactobacillus murinus(L.m)and heat-killed L.muri-nus(H-k L.m)on DA neuronal damage in rats and the underlying mechanisms were investigated.METHODS Male SD rats were randomly divided into five groups:vehicle group,L.m/H-k L.m(1×109 cfu)group,6-OHDH group,6-OHDH + L.m/H-k L.m(1×107 cfu)group,and 6-OHDH + L.m/H-k L.m(1×109 cfu)group.Wild-type and NLRP3 knockout mice were divided into three groups:sham(vehicle),6-OHDH,and 6-OHDH + H-k L.m(1×109 cfu).The model was established after five weeks of pre-administration.Motor ability of experimental mice was assessed by rotarod,mine,and stepping experiments;the expression of dopaminergic neuron markers—tyro-sine hydroxylase(TH),microglial cell markers—ionized calnexin 1(IBA-1),and NOD-like receptor family protein 3(NLRP3)in the substantia nigra was detected by immunohistochemistry and immunofluorescence experi-ments.The expression changes of TH,IBA-1,NLRP3,apoptosis-associated microparticle protein(ASC),cas-pase 1,and inflammatory factors such as interleukin-1β(IL-1β),IL-18,and tumor necrosis factor-α(TNF-α)were detected by immunoblotting experiments.RESULTS H-k L.m ameliorated 6-OHDH-induced motor dysfunctions and loss of substantia nigra DA neurons,while no protec-tion was shown in live L.m treatment.At the same time,H-k L.m reduced the activation of NLRP3 inflammasome in microglia and the secretion of pro-inflammatory factors,thus inhibiting the development of neuroinflammation.Fur-thermore,H-k L.m failed to display its original neuropro-tective properties in NLRP3 inflammasome knockout mice.CONCLUSION H-k L.m conferred neuroprotec-tion against DA neuronal loss via the inhibition of microglial NLRP3 inflammasome activation,these findings provide a promising potential for future applications of L.m,and also beneficial strategy for PD treatment.

The role and mechanism of MMP13 and LRP1 in abnormal autophagy function of articular chondrocytes in patients with Kashin-Beck disease / 中华地方病学杂志

Objective:To investigate the impact of matrix metalloproteinase 13 (MMP13) and low-density lipoprotein receptor-related protein 1 (LRP1) on autophagy of articular chondrocytes in patients with Kashin-Beck disease (KBD).Methods:Human articular cartilage samples obtained from 4 KBD patients and 4 control subjects were collected from Shaanxi Institute for Endemic Disease Prevention and Control, and the expression levels of MMP13 and LRP1 in cartilage tissue were determined using immunohistochemistry (IHC). Chondrocytes were extracted and cultured in vitro, the mRNA and protein expression levels of LRP1 and the autophagy related genes [Beclin 1 (BECN1), microtubule associated protein 1 light chain 3 (LC3)], cartilage injury related genes [MMP13, caspase-3 (CASP3)], chondrocyte differentiation related genes [collagen type Ⅱ alpha 1 chain (COL2A1), and SRY-box transcription factor 9 (SOX9)] were detected by real-time fluorescence quantitative PCR (qRT-PCR) and Western blot (WB), respectively. Chondrocytes from 3 KBD patients were extracted, and MMP13 gene silencing experiment was performed by RNA interference (RNAi) technology, the mRNA and protein expression levels of the above genes were detected by qRT-PCR and WB, respectively. In addition, the antagonist receptor associated protein (RAP) of LRP1 was used to block the LRP1 of human normal chondrocytes (C28/I2 cells), and qRT-PCR and WB were used to detect the mRNA and protein expression levels of LRP1, chondrocyte autophagy, differentiation and cartilage injury related genes, respectively. Results:The IHC results showed that the expression levels of MMP13 (1.67 ± 0.21, 0.59 ± 0.15, 0.51 ± 0.12) in the surface, middle, and deep layers of cartilage tissue of KBD patients were significantly higher than those of control subjects (0.25 ± 0.03, 0.26 ± 0.04, 0.06 ± 0.01), and the differences were statistically significant ( t = - 11.38, P < 0.001; t = - 3.82, - 6.26, P = 0.019, 0.003). The expression levels of LRP1 (0.10 ± 0.02, 0.03 ± 0.01, 0.17 ± 0.03) were significantly lower than those of control subjects (1.63 ± 0.40, 0.44 ± 0.12, 0.34 ± 0.08), and the differences were statistically significant ( t = 6.61, 5.61, 3.64, P = 0.003, 0.005, 0.022). The mRNA and protein expression levels of MMP13, CASP3, SOX9 in chondrocytes of KBD patients were significantly higher than those of control subjects, and the differences were statistically significant ( P < 0.05). The mRNA expression levels of LRP1, LC3, COL2A1 were significantly lower than those of control subjects, and the differences were statistically significant ( P < 0.05). After silencing the MMP13 gene in chondrocytes of KBD patients, there were no significant differences in the mRNA and protein expression levels of LRP1, BECN1, LC3, CASP3, COL2A1, and SOX9 ( P > 0.05). After blocking LRP1 with RAP, the protein expression levels of LRP1, BECN1, LC3, MMP13, COL2A1 and SOX9 in chondrocytes were significantly lower than those in control group ( P < 0.05). Conclusions:There is no direct correlation between MMP13 and abnormal autophagy of articular chondrocytes in KBD patients. After blocking LRP1, the expression of the autophagy related genes BECN1 and LC3 in chondrocytes is decreased.

Effects of ADAM12 abnormal expression on chondrocyte injury and IGFBP-related genes in patients with Kashin-Beck disease / 中华地方病学杂志

Objective:To investigate the role of a disintegrin and metalloprotease 12 (ADAM12) gene in chondrocyte injury in patients with Kashin-Beck disease (KBD) and its impact on genes related to insulin-like growth factor binding protein (IGFBP).Methods:Articular cartilage samples were obtained from 5 patients with KBD and 5 control subjects admitted to Honghui Hospital Affiliated to Xi'an Jiaotong University. Chondrocytes were extracted and cultured in vitro. Quantitative real-time PCR (qRT-PCR) and Western blotting were used to detect the expression levels of ADAM12 mRNA and protein in chondrocytes of patients with KBD and control subjects, respectively. Subsequently, ADAM12 gene overexpression was performed using lentivirus in chondrocytes of patients with KBD. MTT assay was used to detect changes in cell viability after ADAM12 gene overexpression, and qRT-PCR was used to detect the mRNA expression levels of chondrocyte differentiation related genes SRY-box transcription factor 9 (SOX9) and type Ⅱ collagen (COLⅡ), apoptosis-related gene B-cell lymphoma/leukaemia-2-associated X protein (BAX), and anabolic related genes IGFBP3 and IGFBP5. Results:The expression levels of ADAM12 mRNA and protein in chondrocytes of patients with KBD (0.57 ± 0.05, 0.81 ± 0.07) were significantly lower than those of control subjects (1.00 ± 0.00, 1.00 ± 0.00), and the differences were statistically significant ( t = - 24.50, - 3.61, P < 0.05). The results of MTT assay showed that the cell viability of chondrocytes in ADAM12 overexpression group (1.09 ± 0.05) was higher than that in empty vector control group (1.00 ± 0.08), and the difference was statistically significant ( t = 4.12, P = 0.031). The results of qRT-PCR showed that compared with empty vector control group, the mRNA expression levels of IGFBP3 (2.35 ± 0.79 vs 0.96 ± 0.25), IGFBP5 (2.13 ± 0.30 vs 0.98 ± 0.34), SOX9 (2.92 ± 0.51 vs 0.94 ± 0.36) and COLⅡ (6.45 ± 2.81 vs 0.87 ± 0.19) in ADAM12 overexpression group were significantly increased, and the differences were statistically significant ( t = 3.19, 5.16, 6.27, 4.10, P < 0.05); while the expression level of BAX mRNA (0.31 ± 0.06 vs 1.02 ± 0.22) was significantly decreased, and the difference was statistically significant ( t = - 11.16, P < 0.001). Conclusion:The ADAM12 gene may have a role in inhibiting apoptosis and promoting differentiation in chondrocyte injury in patients with KBD, and its overexpression can increase expression of IGFBP3 and IGFBP5.

Microvascular perfusion and cardiac function after revascularization assessed by myocardial contrast echocardiography in patients with acute ST-segment elevation myocardial infarction / 中华心血管病杂志

Objectives: To evaluate microvascular perfusion and left ventricular function in patients with acute ST-segment elevation myocardial infarction after revascularization using myocardial contrast echocardiography (MCE), and to explore clinical influencing factors of abnormal microvascular perfusion in these patients. Methods: This is a cross-sectional study. The analysis was performed among patients admitted to Peking University People's Hospital for acute ST-segment elevation myocardial infarction (STEMI) from June 2018 to July 2021. All patients underwent percutaneous coronary intervention (PCI) and completed MCE within 48 hours after PCI. Patients were divided into normal myocardial perfusion group and abnormal perfusion group according to the myocardial perfusion score. The echocardiographic indexes within 48 hours after PCI, including peak mitral valve flow velocity (E), mean value of early diastolic velocity of left ventricular septum and lateral mitral annulus (Em), left ventricular global longitudinal strain (GLS) and so on, were analyzed and compared between the two groups. Multivariate logistic regression analysis was used to evaluate the influencing factors of myocardial perfusion abnormalities. Results: A total of 123 STEMI patients, aged 59±13 years with 93 (75.6%) males, were enrolled. There were 50 cases in the normal myocardial perfusion group, and 73 cases in the abnormal myocardial perfusion group. The incidence of abnormal myocardial perfusion was 59.3% (73/123). The left ventricular volume index ((62.3±18.4)ml/m2 vs. (55.1±15.2)ml/m2, P=0.018), wall motion score index (WMSI) (1.59 (1.44, 2.00) vs. 1.24(1.00, 1.47), P<0.001) and mitral E/Em (17.8(12.0, 24.3) vs. 12.2(9.2, 15.7), P<0.001) were significantly higher whereas left ventricular global longitudinal strain (GLS) ((-10.8±3.4)% vs. (-13.8±3.5)%, P<0.001) was significantly lower in the abnormal myocardial perfusion group than those in the normal myocardial perfusion group. Multivariate logistic regression analysis showed that left anterior descending (LAD) as culprit vessel (OR=3.733, 95%CI 1.282-10.873, P=0.016), intraoperative no/low-reflow (OR=6.125, 95%CI 1.299-28.872, P=0.022), and peak troponin I (TnI) (OR=1.018, 95%CI 1.008-1.029, P=0.001) were independent risk factors of abnormal myocardial perfusion. As for ultrasonic indexes, deceleration time of mitral E wave (OR=0.979, 95%CI 0.965-0.993, P=0.003), mitral E/Em (OR=1.100, 95%CI 1.014-1.194, P=0.022) and WMSI (OR=7.470, 95%CI 2.630-21.222, P<0.001) were independently related to abnormal myocardial perfusion. Conclusions: The incidence of abnormal myocardial perfusion after PCI is high in patients with acute STEMI. Abnormal myocardial perfusion is related to worse left ventricular systolic and diastolic function. LAD as culprit vessel, intraoperative no/low-reflow and peak TnI are independent risk factors of abnormal myocardial perfusion.

Effect of experiential health education on diet control of college students with type 2 pre diabetes mellitus / 中国学校卫生

Objective@#To understand the influence of experiential health education on diet control of college students with pre diabetes mellitus, and to provide reference for healthy eating habits promotion among college students.@*Methods@#According to the method of random number table, 78 pre diabetic college students screened from Changzhi Medical College from September 2020 to June 2021 were randomly assigned to observation group and control group (39 students in each group). The control group received routine health education for 10 months, once a week for 1 hour each time; On the basis of the above, the observation group received experiential health education once a week for 1 hour, including diet experience, exercise experience, blood sugar test experience and chronic complications experience. Blood glucose and lipids level, body mass index (BMI), dietary control as well as the stages of change for dietary control behavior were compared between the two groups.@*Results@#There was significant difference between the observation group and the control group in the stages of change for dietary control behavior 10 months after intervention ( χ 2=8.92, P <0.05). The compliance score of the observation group was significantly higher than that of the control group in the same period 10 months after the intervention ( t =3.74, P <0.01), the score of the knowledge of diet control in the observation group 10 months after intervention was significantly higher than that in the control group ( t =11.51, P <0.05). The levels of BMI, TG and TC in the observation group were significantly lower than those in the control group at 5 and 10 months after intervention, and the differences were statistically significant ( P <0.05).@*Conclusion@#Experiential health education helps to promote awareness of diabete related knowledge, enhance self management behavior and good diet control habits, and is effective for blood glucose control.