Boosting synergism of chemo- and immuno-therapies via switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis by bisphosphonate coordination lipid nanogranules

Conventional chemotherapy based on cytotoxic drugs is facing tough challenges recently following the advances of monoclonal antibodies and molecularly targeted drugs. It is critical to inspire new potential to remodel the value of this classical therapeutic strategy. Here, we fabricate bisphosphonate coordination lipid nanogranules (BC-LNPs) and load paclitaxel (PTX) to boost the chemo- and immuno-therapeutic synergism of cytotoxic drugs. Alendronate in BC-LNPs@PTX, a bisphosphonate to block mevalonate metabolism, works as both the structure and drug constituent in nanogranules, where alendronate coordinated with calcium ions to form the particle core. The synergy of alendronate enhances the efficacy of paclitaxel, suppresses tumor metastasis, and alters the cytotoxic mechanism. Differing from the paclitaxel-induced apoptosis, the involvement of alendronate inhibits the mevalonate metabolism, changes the mitochondrial morphology, disturbs the redox homeostasis, and causes the accumulation of mitochondrial ROS and lethal lipid peroxides (LPO). These factors finally trigger the ferroptosis of tumor cells, an immunogenic cell death mode, which remodels the suppressive tumor immune microenvironment and synergizes with immunotherapy. Therefore, by switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis, BC-LNPs@PTX provides new insight into the development of cytotoxic drugs and highlights the potential of metabolism regulation in cancer therapy.

Prognostic value of different health-related indicators in elderly patients with diabetes mellitus and coronary heart disease / 公共卫生与预防医学

Objective To analyze the influence of different health-related indicators on the prognosis of elderly patients with diabetes mellitus complicated with coronary heart disease, and to provide theoretical basis for the diagnosis and treatment of diabetes mellitus complicated with coronary heart disease. Methods Among of 456 elderly patients with diabetes mellitus complicated with coronary heart disease admitted to our hospital from December 2018 to December 2020 were selected. According to the occurrence of Major adverse cardiovascular events (MACE) within 1 year after discharge, patients were divided into the control group (no MACE) and the observation group (MACE). The Clinical data of patients including age, gender, BMI, smoking, alcohol consumption, diabetes course, degree of coronary artery stenosis and number of lesions, were collected from the medical record system. Univariate analysis and logistic regression were used to analyze the influence of health indicators such as systolic blood pressure, LEVF, HbA1c, LDL-C, LDH and ALP on the occurrence of MACE in patients with diabetes and coronary heart disease. Spearman correlation analysis was used to analyze the correlation between different health-related indicators and the occurrence of MACE in elderly patients with diabetes mellitus and coronary heart disease. Results A total of 456 elderly patients with diabetes mellitus and coronary heart disease, 122 cases (26.75%) developed MACE. There were no differences in age, male proportion, BMI, smoking and drinking of diabetes course between the two groups (P>0.05). The degree and number of coronary artery stenosis in the observation group were significantly higher than those in the control group (P7.0% (OR=2.617), LDL-C>2.6 mmol/L (OR=2.976) and BUA >420μmol/L (OR=2.341) were independent risk factors for MACE in elderly patients with diabetes mellitus and coronary heart disease (P7.0%, LDL-C >2.6 mmol/L and BUA >420 μmol/L, active treatment should be conducted to improve the prognosis of patients.

Application of artificial intelligence assists bone marrow cytomorphology analysis in the diagnosis and treatment of acute myeloid leukemia / 中华检验医学杂志

Objective:To investigate the value of artificial intelligence (AI) cytomorphologic analysis system in the cytomorphological diagnosis and therapeutic evaluation of acute myeloid leukemia (AML).Methods:Bone marrow smear samples were collected from 150 patients with newly diagnosed and treated acute myeloid leukemia who were inpatients and outpatients at the Department of Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from June 1, 2021 to July 31, 2022 for retrospective analysis. Among them, there were 50 patients in the newly diagnosed group, including 28 males and 22 females, with the onset age of 43.5(32.3,58.8)years. There were 100 patients in the post-treatment group, including 36 males and 64 females, with the onset age of 34.5(23.0,47.0)years. The results from cytomorphology expert were used as the gold standard and the Python 3.6.7 was used for analysis to evaluate the accuracy, sensitivity, and specificity of the AI cytomorphologic analysis system for blast cell recognition in AML diagnosis and treatment.Results:The proportion of blasts in AI analysis of 50 samples in the newly diagnosed group was≥20%, which met the diagnostic criteria of AML. AI analysis of blasts had an accuracy of 90.3%, sensitivity of 85.5%, and specificity of 98.0%. The correlation coefficient between AI and the proportion of blasts analyzed by experts was positively correlated( r=0.882, P<0.001). Meanwhile, in the post-treatment group, the sensitivity and specificity of AI analysis of blasts were 89.7% and 99.2%, respectively. The correlation coefficient between AI and the proportion of blasts analyzed by experts was positively correlated( r=0.957, P<0.001). According to AI analysis data, there are 8 samples in this group whose AI efficacy evaluation results on AML are inconsistent with expert analysis. Conclusion:AI cytomorphologic analysis system has high accuracy, sensitivity and specificity for blast cell recognition in AML morphological diagnosis and therapeutic evaluation.

Reflection on Improving College Students’ Health Literacy from the Perspective of Health Ethics / 中国医学伦理学

Contemporary college students have low levels of health literacy, facing problems such as weak awareness of health care, unhealthy diet habits, insufficient physical activity, and inadequate emergency response to public health emergencies. The reasons may be related to weak personal awareness of health literacy, imperfect health education system, shortage of health literacy education talents, lack of family health literacy education, and the insufficient social investment in health literacy cultivation. Faced with this current situation, the government, universities, families, individuals, and society should respond to the call of "Healthy China 2030" Plan Outline, regard improving college students’ health literacy level as their own responsibility, help them eliminate or reduce the risk factors affecting health, improve their health literacy level and quality of life, and contribute to the Healthy China strategy.

Effect of needle-knife on chondrocyte apoptosis of knee joint in rabbits with knee osteoarthritis based on CircSERPINE2-miR-1271-5P-ERG axis / 中国针灸

OBJECTIVE@#To observe the effect of needle-knife on the chondrocyte apoptosis of knee joint in rabbits with knee osteoarthritis (KOA) based on the CircSERPINE2-miR-1271-5P-E26 specific transformation-related gene (ERG) axis, and to explore the mechanism of needle-knife for KOA.@*METHODS@#Thirty-six New Zealand white rabbits were randomly divided into a normal group, a model group, a needle-knife group and a sham needle-knife group, 9 rabbits in each group. The rabbits in the model group, the needle-knife group and the sham needle-knife group were treated with modified Videman method to prepare KOA model. After successful modeling, the rabbits in the needle-knife group were treated with needle-knife at cord adhesion and nodules near quadriceps femoris tendon and internal and external collateral ligament on the affected knee joint; the rabbits in the sham needle-knife group were treated with sham needle-knife baside the needle insertion point of the needle-knife group (needle-knife was only inserted, without any operation). The treatment was given once a week, 3 times in total. The Lequesne MG behavioral score was used to evaluate the knee joint damage in each group before and after intervention. After intervention, HE staining and transmission electron microscopy were used to observe the cartilage tissue morphology and ultrastructure of chondrocytes in the knee joint in each group; TUNEL method was used to detect the level of chondrocyte apoptosis in the knee joint; real-time fluorescence quantitative PCR was used to detect the expression of CircSERPINE2, miR-1271-5P and ERG mRNA in knee cartilage tissue in each group.@*RESULTS@#After intervention, compared with the normal group, the Lequesne MG behavioral score in the model group was increased (P<0.01). Compared with the model group and the sham needle-knife group, the Lequesne MG behavioral score in the needle-knife group was decreased (P<0.01). In the model group and the sham needle-knife group, the number of chondrocytes and organelles was decreased, the cell nucleus was shrunk, mitochondria was swelling or disappeared; in the needle-knife group, the number of chondrocytes and organelles was increased, the cell nucleus was not obviously shrunk and the mitochondria was not obviously swelling. Compared with the normal group, the level of chondrocyte apoptosis in the model group was increased (P<0.01); compared with the model group and the sham needle-knife group, the level of chondrocyte apoptosis in the needle-knife group was decreased (P<0.01, P<0.05). Compared with the normal group, the expression of CircSERPINE2 and ERG mRNA in the model group was decreased (P<0.01), and the expression of miR-1271-5P mRNA was increased (P<0.01); compared with the model group and the sham needle-knife group, the expression of CircSERPINE2 and ERG mRNA in the needle-knife group was increased (P<0.01), and the expression of miR-1271-5P mRNA was decreased (P<0.01).@*CONCLUSION@#Needle-knife could reduce the knee joint damage and chondrocyte apoptosis in KOA rabbits, which may be related to up-regulating the expression of CircSERPINE2 and ERG mRNA, and inhibiting the expression of miR-1271-5P mRNA.

The value of proton magnetic resonance spectroscopy in the diagnosis of different subtypes of Parkinson's disease and their differential diagnosis from essential tremor / 中华老年医学杂志

Objective:To compare the differences in N-acetylaspartate/creatine(NAA/Cr), N-acetylaspartate/choline(NAA/Cho)and choline/creatine(Cho/Cr)in different brain regions of patients with different motor subtypes of Parkinson's disease(PD)or essential tremor(ET)using proton magnetic resonance spectroscopy( 1H-MRS), and to provide an imaging basis for the diagnosis of different PD subtypes and their differential diagnosis from ET. Methods:92 PD outpatients and inpatients, ET patients and healthy individuals receiving check-ups at our hospital from June 2018 to May 2021were retrospectively enrolled and divided into four groups: tremor-dominant(TD)(n=45), postural instability and gait disorders(PIGD)(n=47), ET(n=44), and healthy controls(n=40). Participant clinical information was collected and bilateral basal ganglia and cerebellar cortex 1H-MRS examinations were performed for each group.Values of NAA/Cr, NAA/Cho and Cho/Cr of the basal ganglia and the cerebellar cortex were compared between the groups. Results:NAA/Cr and NAA/Cho values in the basal ganglia were 1.65±0.19 and 1.55±0.20 for the TD group and 1.48±0.11 and 1.46±0.17 for the PIGD group, respectively, lower than in the control group(NAA/Cr: 1.92±0.28; NAA/Cho: 2.08±0.34)and the ET group(NAA/Cr: 2.10±0.16; NAA/Cho: 2.23±0.23), with statistical significance( P<0.05), whereas Cho/Cr values for the former two groups(TD: 1.07±0.25; PIGD: 1.02±0.13)were higher than in the latter two groups(control: 0.92±0.27; ET: 0.91±0.21), with statistical significance( P<0.05). NAA/Cr values of the basal ganglia in the PIGD group were lower than in the TD group( P<0.05). NAA/Cr, NAA/Cho and Cho/Cr values of the basal ganglia in the ET group were not statistically different compared with those in the control group( P>0.05). In the cerebellar cortex, NAA/Cr(0.72±0.16)and NAA/Cho(0.78±0.14)in the ET group were lower than in the control group(0.92±0.20)and(1.12±0.17), the TD group(0.90±0.14); (1.10±0.13)and the PIGD group(0.89±0.25)and(1.08±0.17)( P<0.05). NAA/Cr, NAA/Cho and Cho/Cr values of the cerebellar cortex for the TD group, the PIGD group and the control group had no statistical difference( P>0.05). Conclusions:1H-MRS can detect brain metabolic changes with damage or loss of neurons in the basal ganglia of PD patients and the cerebellar cortex of ET patients, potentially providing an objective imaging basis for early diagnosis of PD, its subtyping and the differential diagnosis from ET.

Neoadjuvant immune combination therapy for muscle-invasive bladder cancer / 中华泌尿外科杂志

Neoadjuvant therapy leads to the eradication of micrometastasis, thereby providing survival benefit to patients with muscle-invasive bladder cancer (MIBC). In the recent years, multiple clinical trials have corroborated the safety and durability of immune checkpoint inhibitors in the treatment of MIBC. Notably, there is a significantly higher response rate (e.g. pathologic complete response) and comparable occurrence of adverse events in patients treated with neoadjuvant dual immunotherapy, immunotherapy combined with chemotherapy or targeted therapy as compared with that treated with neoadjuvant single-agent immunotherapy. With an overview of breakthroughs in the past years, we believe that immune combination therapy is of great promise and expected to revolutionize the landscape of neoadjuvant therapy of MIBC.

Clinical diagnosis and treatment of tinea of vellus hair / 中华皮肤科杂志

Tinea of vellus hair is caused by dermatophyte infection of vellus hairs, and commonly affects children. It usually occurs on the face, and clinically manifests as annular or semi-annular erythema gradually spreading to the surrounding area, with central clearing and a slightly elevating border covered with papules and papulovesicles. Intense inflammation, which may manifest as pustules, erosions, exudation, scales and crusts, can be observed in patients with severe tinea of vellus hair. Direct microscopy of fungi showed abundant hyphae and/or spores on vellus hairs. Topical antifungal therapy is usually ineffective, and systemic antifungal therapy should be considered. In order to reduce the high rate of missed diagnosis and misdiagnosis, and to improve clinicians′ understanding of this disease, this review summarizes the incidence, clinical manifestations, diagnosis and treatment of tinea of vellus hair.

A preliminary study of radiomics in predicting WHO/ISUP grading of clear cell renal cell carcinoma based on unenhanced CT texture analysis / 中华放射学杂志

Objective:To investigate the value of radiomics based on unenhanced CT texture analysis in predicting the WHO/International Society of Urological Pathology (ISUP) grading of clear cell renal cell carcinoma (ccRCC).Methods:Postoperative pathology-confirmed ccRCC subjects ( n=90) who received CT scanning and had a definite pathological grading in Cancer Hospital of the University of Chinese Academy of Sciences were collected retrospectively from December 2016 to May 2019. The cases were randomly divided into training group ( n=63) and test group ( n=27) as a ratio of 7∶3. All cases were classified into low grade (grades Ⅰ and Ⅱ, n=57) and high grade (grades Ⅲ and Ⅳ, n=37) according to the new pathological grading (WHO/ISUP grading, version 2016) of renal carcinoma. 3D-ROI segmentation was performed on unenhanced CT images and 93 texture features were extracted. The least absolute shrinkage and selection operator (LASSO) regression was used to reduct dimension of texture parameters and then the radiomics score (Rad-score) was established. The logistic regression was used to develop the prediction model with the pathological grading as the gold standard. The ROC curve and calibration curve were used to evaluate the predictive performance of the model, and the area under the curve (AUC), accuracy, sensitivity and specificity were calculated. The Hosmer-Lemeshow test was used to evaluate calibration degree of the model. Results:The 10 non-zero coefficient texture features were screened out through dimension reduction steps. The Rad-score was formed according to the linear combination of these ten features and corresponding coefficients, and then the prediction model was developed. The AUC of the model in training group was 0.933 (95%CI 0.862-1.000), the sensitivity was 92.3%, the specificity was 89.2%, and the model accuracy was 90.5%. The calibration curve showed the good calibration ( P=0.257). The AUC value in test group was 0.875 (95%CI 0.734-1.000), the sensitivity, specificity and accuracy were 72.7%, 87.5% and 81.5%. The calibration curve showed the good calibration ( P=0.125). Conclusion:The radiomics prediction model based on unenhanced CT texture analysis have application potential for the evaluation of WHO/ISUP grading of ccRCC.

HSV-1 H129-Derived Anterograde Neural Circuit Tracers: Improvements, Production, and Applications / 神经科学通报·英文版

Anterograde viral tracers are powerful and essential tools for dissecting the output targets of a brain region of interest. They have been developed from herpes simplex virus 1 (HSV-1) strain H129 (H129), and have been successfully applied to map diverse neural circuits. Initially, the anterograde polysynaptic tracer H129-G4 was used by many groups. We then developed the first monosynaptic tracer, H129-dTK-tdT, which was highly successful, yet improvements are needed. Now, by inserting another tdTomato expression cassette into the H129-dTK-tdT genome, we have created H129-dTK-T2, an updated version of H129-dTK-tdT that has improved labeling intensity. To help scientists produce and apply our H129-derived viral tracers, here we provide the protocol describing our detailed and standardized procedures. Commonly-encountered technical problems and their solutions are also discussed in detail. Broadly, the dissemination of this protocol will greatly support scientists to apply these viral tracers on a large scale.

CircHMGCS1 Activates the NF-κB Signaling Pathway and Promotes Proliferation and Invasion in Cervical Cancer Cells / 中国生物化学与分子生物学报

Circular RNAs play an important role in tumorigenesis. In this study, we explored the role of aberrant expression of circHMGCS1 in cervical cancer cells with TNF-α treatment. RT-qPCR assays showed that circHMGCS1 was highly expressed after TNF-α treatment. And then we investigated the cyclization and stabilization of circHMGCS1 by RNase R and half-life analysis. We further revealed that overexpression of circHMGCS1 promoted the malignancy of cervical cancer cells and the expression of the epithelial-mesenchymal transition (EMT) markers by Transwell analysis, MTT, clone formation and Western blotting. Furthermore, we found that circHMGCS1 activated the NF-κB signaling pathway. Altogether, this study provides an experimental basis for elucidating the role of circHMGCS1 in cervical cancer cells, and provides a potential biomarker for the diagnosis and treatment of cervical cancer.

Molecular Cloning and Functional Analysis of Autophagy-related Gene Atg5 in Planarian Dugesia japonica / 中国生物化学与分子生物学报

Autophagy-related gene 5 (Atg5) plays an essential role in autophagy, the loss of its function impairs neurogenesis and axon regeneration. However, the biological function of Atg5 has not been characterized in planarian. Planarian is an ideal model for the study of brain regeneration. It can regenerate a new brain de novo in 1 week following amputation. To explore the role of Atg5 in planarian brain regeneration, we dissected the molecular characteristics of Atg5 in planarian Dugesia japonica (DjAtg5) and examined its function by RNAi. The full-length cDNA of DjAtg5 is 1 014 bp encoding 284 amino acids. The deduced amino sequence of DjAtg5 contains the functional Pfam domain of ATG5 and highly conserved residues for ATG5-ATG12 interaction. After amputation, the transcrips of DjAtg5 are increased and mainly distributed in the newly regenerated brain on day 3-5 of regeneration. However, knockdown of DjAtg5 by RNAi does not impair the regeneration ability and brain structure reformation, nor affects the neoblasts proliferation. Our results suggest that DjAtg5 participates in re-formation of planarian brain structure following amputation, but it is not an important regulator for planarian regeneration. However, autophagy inhibitor 3-MA can block planarian regeneration, which suggests that autophagy is necessary for planarian regeneration.

Effect of moxibustion on cognitive function and proteins related with apoptosis of hippocampal neurons in rats with vascular dementia / 中国针灸

OBJECTIVE@#To observe the effect of moxibustion on proteins related with apoptosis of hippocampal neurons in rats with vascular dementia (VD), and to explore the possible mechanism of moxibustion on improving VD.@*METHODS@#Thirty SD rats were selected from 100 rats (3 rats were excluded) and randomly divided into a normal group and a sham operation group, 15 rats in each group. The remaining 67 rats were treated with ischemia-reperfusion method at bilateral common carotid artery to establish VD model. The 45 rats with successful VD model were randomly divided into a model group, a moxibustion group and a medication group, 15 rats in each group. On the 7th day after successful modeling, the rats in the moxibustion group were treated with suspended moxibustion at "Guanyuan" (CV 4), "Mingmen" (GV 4) and "Dazhui" (GV 14), 15 min per acupoint, once a day; there was 1 d of rest after 6 d of moxibustion, and the treatment was given for 4 weeks. The rats in the medication group was treated with nimodipine tablets by gavage, 2 mg/kg per day, 3 times a day for 4 weeks. Before and after intervention, the Morris water maze test was used to detect the escape latency of rats in each group; after the intervention, the TUNEL method was used to detect the apoptosis rate of neurons in hippocampal CA1 area; the immunofluorescence double labeling method was used to detect the number of co-expression positive cells of B-cell lymphoma-2 (Bcl-2)/neuronal nuclear antigen (NeuN) and Bcl-2-associated X protein (Bax)/NeuN in hippocampal CA1 area; the immunofluorescence single labeling method was used to detect cytochrome C (cytC) and outer mitochondrial membrane receptor Tom20 (Tom20) in hippocampal CA1 area; the Western blot method was used to detect the p53 upregulated modulator of apoptosis (PUMA) in hippocampus.@*RESULTS@#Before intervention, compared with the normal group and the sham operation group, the escape latency in the model group, the moxibustion group and the medication group was prolonged (@*CONCLUSION@#Moxibustion could improve the cognitive function of VD rats, which may be related to reducing the expression of Bax, cytC, Tom20 and PUMA protein in hippocampal CA1 area, promoting the release of Bcl-2 and inhibiting the apoptosis of hippocampal neurons.

Exploration on Biological Basis Underling Different Syndromes of Nontraumatic Osteonecrosis of Femoral Head Based on Network Pharmacology / 中国实验方剂学杂志

Objective:To explore the biological basis underlying the different syndromes of nontraumatic osteonecrosis of the femoral head (NONFH) according to the molecular interaction network associated with syndromes and the corresponding prescriptions. Method:A total of 30 NONFH patients and 10 healthy controls were enrolled in the present study. The gene expression profiles associated with different syndromes of NONFH were detected by microarray analysis. Then, the molecular interaction networks of the differentially expressed genes of different syndromes were constructed to identify the crucial syndrome-related genes. After collecting the phenotype-related genes and the candidate targets of the corresponding prescriptions of different syndromes from Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine (TCMIP) v2.0 (http://www.tcmip.cn/), the molecular interaction network associated with syndromes and the corresponding prescriptions were constructed and the biological basis of each syndrome was analyzed by functional enrichment analysis. Result:The crucial genes associated with the phlegm-stasis blocking collateral syndrome were mainly involved into the bone and lipid metabolism, and the regulation of immune-inflammation balance and circulation. Consistently, the candidate targets of the corresponding prescription-Jianpi Huogu prescription might play roles in the metabolism of osteogenesis, dissipating phlegm, activating circulation to remove blood stasis, relieving pain and inflammatory response. In addition, our data revealed that the stagnation of meridians syndrome-related genes could be mainly involved into the regulation of circulation and inflammatory response, as well as the metabolism of lipid and bone. Accordingly, the corresponding prescription of this syndrome-Huoxue Tongbi Formula could exert the regulatory effects on osteogenesis and inflammatory response, as well as the activation of the circulation and qi-invigorating. Moreover, the crucial genes associated with the liver and kidney deficiency syndrome played roles in various pathological processes during NONFH, such as the abnormal bone and lipid metabolisms, the immune-inflammation imbalance, and the blocked blood circulation, which were in line with our findings on the pharmacological mechanisms of the corresponding prescription of this syndrome-Bushen Zhuanggu formula. Conclusion:The current study indicated that the phlegm-stasis blocking collateral syndrome may be mainly associated with the abnormal bone and lipid metabolisms. The molecular mechanisms underlying the stagnation of meridians syndrome may be the imbalance of "immune-inflammation" and the blocking circulation. Furthermore, the liver and kidney deficiency syndrome may be not only associated with the abnormal bone and lipid metabolisms, but also implicated into various biological pathways-related to inflammation and circulation. Interestingly, the pharmacological mechanisms of the corresponding prescriptions may be in accord to the biological basis of each syndrome.

Comparative study on icariin and Bu-Shen-Gu-Chi-Wan for alveolar reconstruction in chronic periodontitis in rats / 口腔疾病防治

Objective@#To observe the effects of icariin (ICA) and Bu-Shen-Gu-Chi-Wan on the alveolar bone absorption of chronic periodontitis in rats, and to explore the effect and possible mechanism of ICA in the treatment of chronic periodontitis. @*Methods@#After the establishment of the periodontitis model, the rats were divided into the periodontitis group (group P), ICA high dose group (group H), ICA low dose group (group L) and Bu-Shen-Gu-Chi-Wan treatment group (group B). Each group received treatment for one month and two months, separately, and the serum osteocalcin (OCN) level was measured. Three-dimensional reconstruction was performed after micro computed tomography (micro CT) scanning to measure the bone parameters of specific points, and the distance between the enamel cementum boundary and alveolar crest (CEJ-ABC) was recorded as alveolar bone resorption value. Tissue sections were generated to evaluate the effect of ICA on alveolar bone repair and reconstruction in rats with experimental periodontitis. @*Results@# Compared with the periodontitis group (group P), OCN levels in the serum in treatment groups (groups H, L and B) were decreased significantly (P < 0.05); the values of bone volume/tissue volume (BV/TV) and trabecular number (Tb.N) in treatment groups (groups H, L and B) were significantly higher than that in group P (P < 0.05). Compared with group P, trabecular thickness (Tb.Th) values of groups H and B significantly increased, and trabecular separation (Tb.Sp) of groups H and B significantly decreased (P < 0.05). The changing trend of parameters in group L was the same as that in group H but only after two months of administration. The difference between Tb.Sp values in groups L and P was statistically significant (P < 0.05). Compared with group P, the CEJ-ABC distance significantly reduced in group L (1 month and 2 months after administration), group H (1 month and 2 months after administration), and group B (only 2 months after administration) (P < 0.05).@*Conclusion@#ICA and Bu-Shen-Gu-Chi-Wan improve the alveolar bone resorption in an experimental model of chronic periodontitis in rats, and the mechanism may be related to the regulation of osteocalcin serum levels.

Effect of electroacupuncture on the learning and memory abilities in type 2 diabetic model rats with cognitive impairment / 针灸推拿医学（英文版）

Objective: To observe the effects of electroacupuncture (EA) on the protein and gene expressions of Bax, Caspase-3 and Bcl-2 in cerebral cortex of type 2 diabetic rats with cognitive impairment (CI), and to explore the mechanism of EA in improving the learning and memory abilities. Methods: A total of 100 Sprague-Dawley (SD) rats were divided into a normal group (n=10) and a model group (n=90) by random number table method. Rats in the model group were intraperitoneally injected with a small dose of streptozotocin (STZ) to establish the type 2 diabetic models, after being fed with high-fat and high-sugar diet for 1 month. Twenty CI rats were selected from the 50 successful model rats by the Morris water maze (MWM) test and randomly divided into a model group and an EA group according to the blood glucose level and MWM data (n=10). Rats in the EA group received acupuncture at Zusanli (ST 36), Neiting (ST 44) and Yishu (Extra), of which Zusanli (ST 36) and Neiting (ST 44) were stimulated by EA apparatus, 20 min/time, once a day for 6 d a week and 4 consecutive weeks. The rats in the model and the normal groups were fixed without treatment. After 4-week treatment, the random blood glucose level of the rats was measured; the learning and memory abilities of rats were measured by MWM; terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay was used to detect apoptotic cells; Western blot (WB) and real-time quantitative polymerase chain reaction (RT-qPCR) were used to detect the protein and gene expressions of Bax, Caspase-3 and Bcl-2 in cerebral cortex. Results: After modeling, the random blood glucose level and the escape latency tested by MWM were significantly increased, and the number of crossing the platform tested by the MWM was decreased in the EA and model groups, and were significantly different from those in the normal group (P<0.05 or P<0.01), while the differences between the model group and the EA group were not statistically significant (all P>0.05). After 4-week treatment, the random glucose level and the escape latency tested by MWM were significantly increased (both P<0.05), and the number of crossing the original platform tested by the MWM was significantly reduced (P<0.01), the protein and gene expressions of Bax and Caspase-3 were significantly increased (all P<0.001), the protein and gene expressions of Bcl-2 were significantly reduced (both P<0.001), and the number of neuron apoptosis was significantly increased (P<0.001) in the model group than in the normal group; the random blood glucose level was significantly reduced (P<0.05), the escape latency tested by MWM was significantly shortened (P<0.05), and the number of crossing the original platform tested by MWM was significantly increased (P<0.05), the protein and gene expressions of Bax and Caspase-3 were significantly reduced (all P<0.001), the protein and gene expressions of Bcl-2 were significantly increased (both P<0.001), and the number of neuron apoptosis was significantly reduced (P<0.001) in the EA group than in the model group. Conclusion: EA can improve the learning and memory damages induced by type 2 diabetic model rats with CI; the action mechanism may be achieved via anti-apoptosis.

Activation of Multifidus and Erector Spinae Muscles during Upper Limb Flexion and Abduction in Patients with Nonspecific Low Back Pain / 中国康复理论与实践

Objective:To compare the difference in the onset time of the trunk muscles activity in individuals with and without nonspecific low back pain (NLBP) during upper limb flexion and abduction. Methods:From September to December, 2017, 21 patients with NLBP (NLBP group) and 21 volunteers (control group) participated in this study. Surface electromyography (sEMG) signals were recorded from the anterior deltoid, middle deltoid, multifidus and erector spinae muscles during upper limb flexion and abduction in standing position. Relative differences in the onset times between each muscle and the prime mover were calculated. Results:During upper limb flexion, the right multifidus muscle, bilateral erector spinae were activated in advance of the agonist muscle (anterior deltoid), while the left multifidus muscle was delayed relative to the agonist muscle in both groups. The onset time of the right erector spinae was significantly delayed in NLBP group than in the control group (t = -2.393, P = 0.019). During upper limb abduction, bilateral multifidus muscle and bilateral erector spinae were activated in advance of the agonist muscle (middle deltoid) in the control group. Additionally, in NLBP group, the left erector spinae was activated in advance of the agonist muscle, bilateral multifidus and right erector spinae were delayed relative to the agonist muscle. There was no significant difference in the relative onset time between both groups (t < 1.393, P > 0.05). Conclusion:During upper limb flexion and abduction, the trunk muscles of the lower back are activated in advance for healthy individuals, while individuals with NLBP have a possibly delayed activation of trunk muscles.

Effects of Porphyromonas gingivalis infection with different fimA genotypes on the secretion of IL-1β, IL-6, and TNF-α by human umbilical vein endothelial cells / 口腔疾病防治

Objective@#To study the effects of Porphyromonas gingivalis (P. g) infection with I, II and IV fimA genotypes on the expression of IL-1beta, IL-6 and TNF-alpha in human umbilical vein endothelial cells (HUVECs). @*Methods @#HUVECs infected with different fimA genotypes were divided into the fimA type I stimulation group, fimA type II stimulation group, fimA type IV stimulation group. In addition, a positive control group (E. coli LPS stimulation) and negative control group (cell culture medium only) were included. Cell proliferation was detected by MTT assay, and cell apoptosis was detected by flow cytometry. IL-1β, IL-6, TNF-α levels in the supernatant of HUVECs after P. g stimulation were assessed by ELISA at 2 h, 6 h and 24 h.@*Results @#HUVECs were infected by P. g with fimA type I,fimA type II and LPS for 24 h. Cell proliferation was inhibited compared with the negative control group (P < 0.05), but there was no significant difference in the apoptosis rate between P. g infection and the negative control group. IL-1β levels in cell culture supernatants were higher at 2th than 6 and 24 h after stimulation of HUVECs with different fimA genotypes, while the IL-6 levels were higher at 24 h than the other time, while the TNF-α levels were no significant difference at every time. After fimA type II and IV P. g infection, IL-1β, IL-6, and TNF-α levels were increased compared with fimA type I P. g (P < 0.05).@*Conclusion @# Different P. g fimA genotypes have different effects on stimulating HUVECs to induce dysfunction. Here, fimA type II and IV P. g exhibit a strong ability to upregulate the secretion of IL-1β, IL-6 and TNF-alpha.

Moxibustion at acpoints of governor vessel on regulating PI3K/Akt/mTOR signaling pathway and enhancing autophagy process in APP/PS1 double-transgenic Alzheimer's disease mice / 中国针灸

OBJECTIVE@#To observe the eliminating effects of moxibustion at "Baihui" (GV 20), "Fengfu" (GV 16) and "Dazhui" (GV 14) on amyloid β-peptide (Aβ) in brain of the amyloid precursor protein/presenili1 (APP/PS1) double-transgenic mice with Alzheimer's disease (AD) by regulating the phosphoinositide 3-kinases/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway.@*METHODS@#A total of 60 APP/PS1 double-transgenic mice with AD were randomly divided into a model group, a moxibustion group, a rapamycin group and a combination group (treated with moxibustion and inhibitor), 15 mice in each group, another 15 male C57BL/6J mice with same age and background were selected as the control group. In the moxibustion group, pressing moxibustion was applied at "Baihui" (GV 20) while the mild moxibustion was applied at "Fengfu" (GV 16) and "Dazhui" (GV 14). The treatment was manipulated for 20 min each time, once a day for 2 weeks. In the rapamycin group, rapamycin (2 mg/kg) was given by intraperitoneal injection once a day for 2 weeks. On the basis of the treatment in the moxibustion group, 3-methyladenine (1.5 mg/kg) was given by intraperitoneal injection once a day for 2 weeks. The mice in the control and the model group received normal diet and no intervention was given for 2 weeks. Immunohistochemica method was used to measure the levels of Aβ in the cerebral cortex and hippocampal, transmission electron microscopy was used to observe the formation of autophagosome in hippocampus, and Western blot method was used to observe the levels of PI3K, Akt, p-Akt, mTOR and p-mTOR in hippocampus.@*RESULTS@#Compared with the control group, the levels of Aβ in the cerebral cortex and hippocampal were increased in the model group (0.05）. Compared with the rapamycin group, the levels of Aβ in the cerebral cortex and hippocampal were increased in the combination group (<0.01). In the model group, the cytoplasmic utophagic vacuoles and organelles of neuron were reduced. In the moxibustion group, the utophagic vacuoles were increased, and the organelles showed deformation and atrophy. In the rapamycin group, the utophagic vacuoles were widely disturbed and few deformed organelles were found. In the combination group, few utophagic vacuoles were found and additional organelles showed deformation and atrophy. Compared with the control group, the levels of PI3K、Akt、p-Akt、mTOR and p-mTOR were increased in the model group (all <0.01). Compared with the model group, the levels of PI3K、Akt、p-Akt、mTOR and p-mTOR were reduced in the moxibustion group, the rapamycin group and the combination group (all <0.01). Compared with the moxibustion group, the levels of PI3K、Akt、and p-mTOR were increased in the rapamycin group and the levels of PI3K、Akt、p-Akt、mTOR and p-mTOR were increased in the combination group (all <0.01). Compared with the rapamycin group, the levels of PI3K、Akt、p-Akt、mTOR and p-mTOR were increased in the combination group (<0.01).@*CONCLUSION@#Moxibustion at acupoints of governor vessel can enhance the autophagy process on Aβ in brain of the APP/PS1 double-transgenic AD mice, which may be associated with its effects on inhibiting the abnormal activation of PI3K/Akt/mTOR signaling pathway.

Research progress on the T cell receptor CDR3 spectral sequence of periodontitis / 口腔疾病防治

@#Periodontitis is a chronic inflammatory and destructive disease of periodontal support tissue initiated by plaque microorganisms, and its pathogenesis and progression are closely related to the immune response of the host, in which T cells play an important role in the periodontitis immune response. This article will start with the T cell immune response and the characteristics of the T cell receptor complementarity-determining region 3 (TCR CDR3) spectrum and will review the relationship between the characteristics of the TCR CDR3 spectrum and the pathogenesis of periodontitis to provide some new ideas for the studies of pathogenesis and the clinical personalized treatment of periodontitis. The study on the TCR CDR3 spectrum of periodontitis by reviewing the literature suggests that there is an oligoclonal accumulation of T cells and biased access of Variable (V) and Joining (J) genes in local lesions of periodontitis; moreover, the repeated use of nucleotide sequences and a conservative amino acid motif were found in the CDR3 region, which suggests that the characteristics of the TCR CDR3 group library play an important role in the immune pathogenesis of periodontitis.