Research progress of targeted degradation of Mycobacterium tuberculosis proteins / 药学学报

Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis (Mtb), is still one of the significant threats to human life. In recent years, the continuous exploration of small molecule inhibitors represented by bedaquinoline has brought new vitality into the field of tuberculosis. However, small molecule inhibitors will inevitably occur acquired drug resistance during clinical medication. As a new pharmacological mechanism, targeted protein degradation (TPD) achieves efficacy by destroying rather than inhibiting protein targets. It might be an excellent strategy to develop anti-tuberculosis drugs based on the TPD concept to solve drug resistance. This article reviews the protein degradation pathways of Mtb, such as the Pup proteasome system and the ClpP-ClpC1 complex enzyme system. The future development of these strategies into TPD drugs was prospected and summarized.

Association of greenness, nitrogen dioxide with the prevalence of hypertension among the elderly over 65 years old in China / 中华预防医学杂志

Objective: To investigate the association of mixed exposure to greenness and nitrogen dioxide(NO2) and hypertension among the older adults aged 65 years and over in China. Methods: The study subjects were from the Chinese Longitudinal Healthy Longevity Survey from 2017 to 2018. A total of 15 423 older adults aged 65 years and over meeting the criteria were finally included in the study. A questionnaire survey was used to collect information on demographic characteristics, lifestyle habits and self-reported prevalence of hypertension. Blood pressure values were obtained through physical examination. The level of normalized difference vegetation index(NDVI) was measured by the Medium-resolution Imaging Spectral Radiator(MODIS) of the National Aeronautics and Space Administration(NASA). The concentration of NO2 was from China's surface air pollutant data set. Meteorological data was from NASA MERRA-2. The exposure to NDVI and NO2 for each study subject was calculated based on the area within a 1 km radius around their residence. The association between mixed exposure of NDVI and NO2 as well as their interaction and hypertension in older adults was analyzed by using the multivariate logistic regression model. The restrictive cubic spline(RCS) function was used to explore the exposure-response relationship between greenness and NO2 and the risk of hypertension in study subjects. Results: The mean age of 15 423 older adults were (85.6±11.6). Women accounted for 56.3%(8 685/15 423) and 55.6%(8 578/15 423) lived in urban areas. The mean time of residence was (60.9±28.5) years. 59.8% of participants were with hypertension. The mean NDVI level was 0.41±0.13, and the mean NO2 concentration was (32.18±10.36) μg/cm3. The results of multivariate logistic regression analysis showed that NDVI was inversely and linearly associated with the hypertension in older adults, with the OR(95%CI) value of 0.959(0.928-0.992). Compared with the T1 group of NDVI, the risk of hypertension was lower in the T3 group, with the OR(95%CI) value of 0.852(0.769-0.944), and the trend test was statistically significant(P<0.05). Compared with the T1 group of NO2, the risk of hypertension was higher in the T2 and T3 groups, with OR(95%CI) values of 1.160(1.055-1.275) and 1.244(1.111-1.393), and the trend test was statistically significant (P<0.05). The result of the RCS showed that NDVI was inversely and linearly associated with hypertension in older adults. NO2 was nonlinearly associated with hypertension in older adults. The interaction analysis showed that NDVI and NO2 had a negative multiplicative interaction on the risk of hypertension, with OR(95%CI) value of 0.995(0.992-0.997). Conclusion: Exposure to greenness and NO2 are associated with hypertension in older adults.

Association of plasma vitamin B12 level with plasma uric acid level among the elderly over 65 years old in 9 longevity areas of China / 中华预防医学杂志

Objective: To investigate the association of plasma vitamin B12 level with plasma uric acid level among the elderly over 65 in 9 longevity areas of China. Methods: The elderly over 65 years old with complete information on plasma vitamin B12 and plasma uric acid from Healthy Aging and Biomarkers Cohort Study (2017 to 2018) were recruited in this study. Information on socio-demographic characteristics, life styles, diet intake, and health status were collected by questionnaire and physical examination; and fasting venous blood was collected to detect the levels of plasma vitamin B12, uric acid and other indicators. Multiple linear regression models were used to analyze the association of plasma vitamin B12 level per interquartile range increase with plasma uric acid level. The association trend of plasma vitamin B12 level with plasma uric acid level was described by restrictive cubic splines fitting multiple linear regression model. Multiple logistic regression models were used to analyze the association of plasma vitamin B12 level stratified by quartiles with hyperuricemia. Results: A total of 2 471 participants were finally included in the study, the age was (84.88±19.76) years old, of which 1 291 (52.25%) were female. The M (Q1, Q3) level of plasma vitamin B12 was 294 (203, 440) pg/ml and the plasma uric acid level was (341.01±90.46) μmol/L. A total of 422 participants (17.08%) were defined with hyperuricemia. The results of multiple linear regression model showed that there was a positive association of plasma vitamin B12 level with plasma uric acid level after adjustment for covariates (P<0.05). An IQR increase in plasma vitamin B12 (237 pg/ml) was associated with a 6.36 (95%CI: 2.00-10.72) μmol/L increase in the plasma uric acid level. The restrictive cubic splines curve showed a positive linear association of log-transformed plasma vitamin B12 with uric acid level (P<0.001). Conclusion: There is a positive association of plasma vitamin B12 level with plasma uric acid level among the elderly over 65 years old in 9 longevity areas of China.

A qualitative research on the responsibility understanding and difficult experience of respiratory nurses in the management of chronic obstructive pulmonary disease patients / 中国实用护理杂志

Objective:To explore the responsibilities of respiratory nurses in the management of chronic obstructive pulmonary disease (COPD) patient and the difficulties in disease management, so as to provide reference basis for formulating COPD management training strategies for respiratory nurses.Methods:Using phenomenological methodology, 14 nurses from the Department of Respiratory and Critical Care Medicine in the General Hospital of Ningxia Medical University and the First People′s Hospital of Yinchuan were interviewed in a personal semi-structured way from May to August 2021, and the data were sorted and analyzed according to Colaizzi 7-step analysis method.Results:Nurses′understanding of the responsibilities of COPD patient management could be summarized into five themes: dynamic monitoring and management of patients′ health, nursing decision-making of sudden changes in patients′ condition, implementation of patients′ out of hospital follow-up, promotion of improvement of patients′ self-management behavior, and cooperation among multidisciplinary team members. The difficult experience of nurses in the management of COPD patients abstracted five themes: lack of professional knowledge of COPD management, lack of clinical nursing decision-making authority, lack of human and financial support for follow-up, lack of communication skills with patients, and lack of multidisciplinary team formation in the hospital.Conclusions:Respiratory nurses have a clear understanding of the responsibilities of COPD patient management, but there are multiple difficulties in performing their responsibilities. We should pay attention to the responsibility positioning and difficulty support of nurses′ COPD management, and formulate targeted training strategies to promote the improvement of COPD nursing quality.

Review of advances in chemotherapy for thyroid cancer / 中华内分泌外科杂志

The incidence of thyroid cancer has continued to increase. Most thyroid cancer patients have good prognosis, but there are still some patients who will develop into the middle or late stage. The status of cytotoxic treatment in thyroid cancer treatment is controversial. Chemotherapy, as a classical malignant tumor treatment, has its unique significance for the special type and the special period of thyroid cancer. Chemotherapy can be an option for systemic treatment if no other treatment is available for patients of differentiated thyroid carcinoma refractory to radiodine in rapid progression and life-threatening period. For patients of anaplastic thyroid cancer in progression period, chemotherapy can be selected if there are no other treatments in clinical trials. And "Chemical therapy plus" treatment model might play an important role in thyroid treatment, because with the development of targeted drugs and immunotherapy, chemotherapy combined with other treatments can reduce the dosage of chemotherapy drugs to reduce the toxic side effect, and can improve other therapeutic effects.

Progress in diagnosis and treatment of autoimmune pancreatitis / 国际外科学杂志

Autoimmune pancreatitis (AIP) is a chronic inflammatory disease of the pancreas associated with autoimmune and characterized by pancreatic enlargement and irregular stenosis of the pancreatic duct. Due to its similar characteristics with pancreatic cancer, and some AIP patients complicated with pancreatic cancer, it has become a difficulty in clinical diagnosis and treatment. Its pathogenesis is unknown and its curative effect is uncertain. In recent years, the pathological mechanism, diagnostic system and therapeutic methods of this disease have been updated constantly. This paper summarizes the research progress of the above aspects.

Exploration and example interpretation of real-world herbal prescription classification based on similarity matching algorithm / 中国中药杂志

In observational studies, herbal prescriptions are usually studied in the form of "similar prescriptions". At present, the classification of prescriptions is mainly based on clinical experience judgment, but there are some problems in manual judgment, such as lack of unified criteria, labor consumption, and difficulty in verification. In the construction of a database of integrated traditional Chinese and western medicine for the treatment of coronavirus disease 2019(COVID-19), our research group tried to classify real-world herbal prescriptions using a similarity matching algorithm. The main steps include 78 target prescriptions are determined in advance; four levels of importance labeling shall be carried out for the drugs of each target prescription; the combination, format conversion, and standardization of drug names of the prescriptions to be identified in the herbal medicine database; calculate the similarity between the prescriptions to be identified and each target prescription one by one; prescription discrimination is performed based on the preset criteria; remove the name of the prescriptions with "large prescriptions cover the small". Through the similarity matching algorithm, 87.49% of the real prescriptions in the herbal medicine database of this study can be identified, which preliminarily proves that this method can complete the classification of herbal prescriptions. However, this method does not consider the influence of herbal dosage on the results, and there is no recognized standard for the weight of drug importance and criteria, so there are some limitations, which need to be further explored and improved in future research.

The therapeutic effect of Balanophora polysaccharide on acetic acid gastric ulcer in rats and its mechanism / 中国药理学通报

Aim To study the therapeutic effect of Balanophora polysaccharide(BPS)on gastric ulcer(GU)induced by acetic acid in rats and to investigateits mechanisms. Methods Sixty male SD rats were randomly divided into sham-operated group, GU model group, omeprazole positive group(3.6 mg·kg-1), and low, medium and high dose of BPS treatment groups(100, 200 and 400 mg·kg-1). The GU model group was prepared by acetic acid cautery method, and the morphology and pathological changes of ulcers were observed by visual observation combined with HE staining, and the ulcer area and inhibition rate were measured and calculated; superoxide dismutase(SOD)activity, malondialdehyde(MDA)content and glutathione peroxidase(GSH-PX)activity were measured by enzymatic assay; tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)content were detected by ELISA. The expression levels of epidermal growth factor(EGF)and epidermal growth factor receptor(EGFR)were measured by immunohistochemistry staining and Western blot. Results Compared with the sham-operated group, obvious ulcer damage was seen in the model group. Compared with the model group, the BPS-treated group showed a significant reduction in ulcer area, an increase in SOD and GSH-PX activity and EGF and EGFR expression levels, and a significant decrease in MDA, TNF-α and IL-6 content. Conclusions BPS has a therapeutic effect on GU in rats, and its mechanism may be related to the inhibition of oxidative stress, suppression of inflammatory stimuli and promotion of regenerative repair of gastric mucosa.

Effects of total saponins from Trillium tschonoskii maxim on cognition impairment and mitochondrial autophagy in aging rats induced by D-Gal / 中国药理学通报

Aim To investigate the effects of total saponins from Trillium tschonoskii maxim(TST)on cognitive impairment and mitochondrial autophagy in aging rats induced by D-galactose(D-gal). Methods Male SD rats were randomly divided into normal control group,model group(D-gal,subcutaneous injection),intervention group(TST,low,medium and high dose groups by intragastric administration),with 10 rats in each group,and administered for 6 weeks. Morris water maze was used to evaluate the cognitive function. HE and Nissl staining were used to test the hippocampal and brain cortex morphology. Immunohistochemistry staining was applied to detect the localization expression of Pink1 and Parkin. Western blot was employed to detect the expressions of Pink1,Parkin,LC3-Ⅱ,p62 and Beclin1. Results Compared with the normal control group,the escape latency time was prolonged and the number of crossing platform decreased in D-gal model group(P<0.05). The number of neurons in hippocampus significantly decreased. The positive cells labeled by Pink1 and Parkin staining in hippocampus significantly decreased. The expressions of Pink1,Parkin,LC3-Ⅱ and Beclin1 were markedly reduced,while the expression of p62 was significantly raised(P<0.05). Compared with D-gal model group,the escape latency time of TST dose groups was shortened,the Times of crossing the platform was more,and the time of staying in the platform quadrant increased(P<0.05). The number of neurons in hippocampus significantly increased. The positive cells labeled by Pink1 and Parkin staining in hippocampus significantly increased. The expressions of Pink1,Parkin,LC3-Ⅱ and Beclin1 in hippocampus were apparently up-regulated,while the protein expression of p62 was evidently down-regulated(P<0.05). Conclusions TST has neuroprotective effects on the learning and memory capacities in aging rats induced by D-gal,which may be related to the increasing levels of Pink1,Parkin,LC3-Ⅱ and Beclin1 proteins and the activation of mitochondrial autophagy.

Discovery of a highly potent and orally available importin-β1 inhibitor that overcomes enzalutamide-resistance in advanced prostate cancer

Nuclear transporter importin-β1 is emerging as an attractive target by virtue of its prevalence in many cancers. However, the lack of druggable inhibitors restricts its therapeutic proof of concept. In the present work, we optimized a natural importin-β1 inhibitor DD1 to afford an improved analog DD1-Br with better tolerability (>25 folds) and oral bioavailability. DD1-Br inhibited the survival of castration-resistant prostate cancer (CRPC) cells with sub-nanomolar potency and completely prevented tumor growth in resistant CRPC models both in monotherapy (0.5 mg/kg) and in enzalutamide-combination therapy. Mechanistic study revealed that by targeting importin-β1, DD1-Br markedly inhibited the nuclear accumulation of multiple CRPC drivers, particularly AR-V7, a main contributor to enzalutamide resistance, leading to the integral suppression of downstream oncogenic signaling. This study provides a promising lead for CRPC and demonstrates the potential of overcoming drug resistance in advanced CRPC via targeting importin-β1.

Surgical treatment for obstructive hypertrophic cardiomyopathy: a five-year single-center experience of 421 cases / 中华外科杂志

Objectives: To examine the short-term and mid-term effects of surgical treatment of obstructive hypertrophic cardiomyopathy (HCM) in one center. Methods: The perioperative data and short-term follow-up outcomes of 421 patients with obstructive HCM who received surgical treatment at Department of Cardiac Surgery, Zhongshan Hospital, Fudan University from January 2017 to December 2021 were analyzed retrospectively. There were 207 males and 214 females, aged (56.5±11.7) years (range: 19 to 78 years). Preoperative New York Heart Association (NYHA) classification included 45 cases of class Ⅱ, 328 cases in class Ⅲ, and 48 cases in class Ⅳ. Fifty-eight patients were diagnosed with latent obstructive HCM and 257 patients had moderate or more mitral regurgitation with 56 patients suffering from intrinsic mitral valve diseases. All procedures were completed by a multidisciplinary team, including professional echocardiologists involving in preoperative planning for proper mitral valve management strategies and intraoperative monitoring. A total of 338 patients underwent septal myectomy alone, and 59 patients underwent mitral valve surgery along with myectomy. A single transaortic approach was used in 355 patients, and a right atrial-atrial septal/atrial sulcus approach was used in 51 other patients. Long-handled minimally invasive surgical instruments were used for the procedures. Student t test, Wilcoxon rank sum test, χ2 test or Fisher exact test were used to compare the data before and after surgery. Results: The aortic cross-clamping time of septal myectomy alone was (34.3±8.5) minutes (range: 21 to 94 minutes). Eighteen patients had intraoperative adverse events and underwent immediate reoperation, including residual obstruction (10 patients), left ventricular free wall rupture (4 patients), ventricular septal perforation (3 patients), and aortic valve perforation (1 patient). Four patients died during hospitalization, and 11 patients developed complete atrioventricular block requiring permanent pacemaker implantation. After discharge, 384 (92.1%) patients received a follow-up visit with a median duration of 9 months. All follow-up patients survived with significantly improved NYHA classifications: 216 patients in class Ⅰ and 168 patients in class Ⅱ (χ2=662.73, P<0.01 as compared to baseline). At 6 months after surgery, follow-up echocardiography showed that the thickness of the ventricular septum ((13.6±2.5) mm vs. (18.2±3.0) mm, t=23.51, P<0.01) and the peak left ventricular outflow tract gradient ((12.0±6.3) mmHg vs. (93.4±19.8) mmHg, 1 mmHg=0.133 kPa, t=78.29, P<0.01) were both significantly lower than baseline values. Conclusion: The construction of the surgical team (including echocardiography experts), proper mitral valve management strategies, identification and management of sub-mitral-valve abnormalities, and application of long-handled minimally invasive surgical instruments are important for the successful implementation of septal myectomy with satisfactory short-and medium-term outcomes.

Risk factor analysis of 20-year follow-up of 2038 cases of thyroid cancer: a single center study / 中华内分泌外科杂志

Objective:To discuss the long-term survival and risk factors of thyroid cancer in the real world in China.Methods:The clinical data of thyroid cancer patients who underwent initial surgery from Apr. 1998 to Dec. 2018 were retrospectively analyzed, including patients’sex, age, surgical records, pathology, hospitalization records and follow-up. According to the prognosis, the patients were divided into disease-free survival group and recurrence/metastasis/death group. Univariate analysis and multivariate regression analysis were conducted to analyze the risk factors affecting the prognosis of thyroid cancer. The clinical features and prognostic risk factors of thyroid cancer patients were investigated.Results:A total of 2038 cases were collected, and the longest follow-up time was more than 20 years. A total of 1876 cases were included in the study, 162 cases were lost, and the rate of follow-up was 7.9%. Among them, 1858 survived, the overall survival rate was 99.04%; 18 died, and the overall mortality rate was 0.96%. According to the prognosis of thyroid cancer, the patients were divided into 2 groups, including 1808 cases in the disease-free survival group and 68 cases in the relapsed-metastatic-death group. The study found that there were statistical differences between the two groups in terms of patients’age [ (45.40±11.016) vs (51.53±15.199, P=0.000) , the male ratio (32.854%, 48.529%, P=0.001) , whether tumor breaks through capsule (20.077%, 33.823%, P=0.006) , central lymph node metastasis (48.834%, 70.588%, P=0.001) and lateral lymph node metastasis (31.084%, 55.882%, P=0.000) , and there was no difference between the number of tumor lesions. Conclusion:Thyroid cancer has a good prognosis, but according to the characteristics of patients with thyroid cancer in my country, it should still be treated early in the clinic, and the standardization and thoroughness of surgery should be adhered to during the treatment.

Oxygen Metabolism-induced Stress Response Underlies Heart-brain Interaction Governing Human Consciousness-breaking and Attention / 神经科学通报·英文版

Neuroscientists have emphasized visceral influences on consciousness and attention, but the potential neurophysiological pathways remain under exploration. Here, we found two neurophysiological pathways of heart-brain interaction based on the relationship between oxygen-transport by red blood cells (RBCs) and consciousness/attention. To this end, we collected a dataset based on the routine physical examination, the breaking continuous flash suppression (b-CFS) paradigm, and an attention network test (ANT) in 140 immigrants under the hypoxic Tibetan environment. We combined electroencephalography and multilevel mediation analysis to investigate the relationship between RBC properties and consciousness/attention. The results showed that RBC function, via two independent neurophysiological pathways, not only triggered interoceptive re-representations in the insula and awareness connected to orienting attention but also induced an immune response corresponding to consciousness and executive control. Importantly, consciousness played a fundamental role in executive function which might be associated with the level of perceived stress. These results indicated the important role of oxygen-transport in heart-brain interactions, in which the related stress response affected consciousness and executive control. The findings provide new insights into the neurophysiological schema of heart-brain interactions.

Computer assisted design of lobulated perforator flap based on descending branch of lateral circumflex femoral artery in reconstruction of heel defects / 中华显微外科杂志

Objective:To investigate the feasibility and clinical effect of the computer assisted design of the lobulated perforator flap based on the descending branch of lateral circumflex femoral artery(d-LCFA) to reconstruct the soft tissue defects of heel.Methods:From October 2014 to November 2016, a computer assisted virtual technology was used to simulate the process of pre-operative design, isolation, and harvest of d-LCFA perforating flaps. This method was used to guide the design and harvest of the flap of d-LCFA in the repair of large-area soft tissue defects of the heel in all of the 5 patients. One patient received a combine flap of the d-LCFA flap and the perforating branch of the inferior abdominal artery flap(DIEPF). Heel appearance and function were reconstructed in phase I together with the repair of the defect. Donor site was directly sutured. The recovery effect was followed-up in the clinic.Results:The 3D visualised model of the vessels in the donor area for quadriceps artery was successfully established in all 5 patients, and the design and removal of the perforating flap were successfully guided. All the 10 flaps survived successfully in 5 patients, except 1 patient had a backflow disorder at the distal end of the inferior epigastric artery perforator flap, with partial necrosis and II grafting. After 6 to 12 months of follow-up(mean, 8.7 months), the flap showed good in colour and texture, with satisfactory heel appearance. The donor site was left with a linear scar.Conclusion:Computer assisted design technology can effectively help in the design of the polyfoliate perforator flap pedicled with d-LCFA, using this technique to assist the design and repair of large area soft tissue defect of heel could reconstruct the shape of heel in phase I and restore the function of the heel to the maximum extent.

Analysis of metabolic indexes and other characteristics in patients with primary aldosteronism / 中国综合临床

Objective:To analyze the changes of metabolic indexes and other characteristics in patients with primary aldosteronism (PA) and improve the understanding of PA.Methods:From January 2017 to August 2020, 91 PA patients who were clearly diagnosed and met the inclusion conditions in Tangshan workers Hospital, Hebei Medical University were selected as the observation object (PA group), and 112 patients diagnosed as essential hypertension (EH) in the same period were included as the control (EH group). A retrospective case-control study was conducted to compare the differences of blood glucose, blood lipid, homocysteine, blood potassium, creatinine, uric acid, aldosterone, renin, plasma aldosterone to renin ratio (ARR), blood pressure and waist circumference between the two groups. The measurement data of normal distribution were compared by independent sample t-test. The non normal distribution data are represented by M (Q 1, Q 3), and the rank sum test is used for inter group comparison. Comparison of counting data χ2 inspection. Logistic regression was used in multivariate analysis. Results:Univariate analysis showed that serum potassium, renin and ARR were (3.37±0.39) mmol/L, 1.61 (0.34, 7.23) ng/L and 96.85 (26.06, 506.10) in PA group and (3.91±0.59) mmol/L, 12.81 (1.90, 82.45) ng/L and 13.22 (1.06, 54.63) in EH group ( t=3.35, z=6.24, z=55.40, all P<0.001). In PA group, systolic blood pressure was (190.80±20.30) mmHg, diastolic blood pressure was (117.70±12.89) mmHg, waist circumference was (91.67±9.38) cm, and in EH group, systolic blood pressure was (177.01±12.89) mmHg, diastolic blood pressure was (101.39±9.34) mmHg, waist circumference was (86.59±9.07) cm. There were significant differences between the two groups ( t=5.88, 10.44, 3.90; all P<0.001). Multivariate logistic regression analysis showed that waist circumference (OR=1.065, 95% CI 1.007-1.118, P<0.001), systolic blood pressure (OR=1.053, 95% CI 1.034-1.077, P<0.001), diastolic blood pressure (OR=1.054, 95% CI 1.031-1.077, P<0.001), and ARR (OR=1.170, 95% CI 1.115-1.228, P<0.001) were the risk factors for PA. Conclusion:Compared with essential hypertension, PA patients have higher blood pressure, ARR and waist circumference, lower blood potassium and renin levels. Systolic blood pressure, diastolic blood pressure, ARR and waist circumference are the risk factors of PA. Strengthening the screening and treatment of PA in high-risk groups is helpful to better avoid the risk of target organ damage.

Effects of Zhongfeng capsule on autophagy related proteins expressions of brain tissue in rats with cerebral ischemia/reperfusion injury / 中国应用生理学杂志

Objective: To investigate the effects of Zhongfeng capsule on the autophagy-related proteins expression in rats with cerebral ischemia/reperfusion injury (CI/ RI), and to explore its neural protection mechanisms of the decoction. Methods: Rat middle cerebral artery ischemia/reperfusion injury model (ischemia for 2 h, reperfusion for 24 h) was prepared by the improved line plug method. Sixty male SD rats were randomly divided into sham operation group, model group, butylphthalide group(0.054 g/kg), Zhongfeng capsule high-dose groups (1.08 g/kg), Zhongfeng capsule middle-dose groups (0.54 g/kg), Zhongfeng capsule low-dose groups (0.27 g/kg), with 10 rats in each group. Rats were treated with Zhongfeng capsule by gavage once a day for 10 days. The rats were sacrificed and the brain tissue was obtained after the experiment in each group. Score neurological deficit was evaluated after 24 h of the last intervention in rat of each group. The pathological changes of brain tissue were observed by HE staining. The serum levels of estradiol (E2) and follicle stimulating hormone (FSH) were determined by ELISA. The expressions of key genes and proteins of PI3K/Akt/Beclin1 signaling pathway in brain tissue were detected by qRT-PCR and Western blot respectively. Results: Compared with the sham operation group, the body weight and protein expressions of p-PI3k and p-Akt in brain tissue of rats were decreased significantly in the model group, while the brain index, neurological deficit score, gene and protein expressions of Beclin1 and LC3 were increased markedly in the model group(P＜0.05 or P＜0.01). In the model group, nerve cells of brain tissue were loosely packed, interstitial edema, triangular in shape, nuclear pyknosis and dark-blue staining were observed. Compared with the model group, the body weight of rats was increased obviously, the neurological deficit score was decreased significantly and the pathological injury of brain tissue was alleviated evidently in high-dose of Zhongfeng capsule group (P＜0.05). The brain index, the gene and protein expressions of Beclin1 and LC3 were decreased apparently in Zhongfeng capsule treatment groups(P＜0.05 or P＜0.01), while the expressions of p-PI3k and p-Akt in brain tissue were increased evidently in Zhongfeng capsule treatment groups(P＜0.05 or P＜0.01). Conclusion: Zhongfeng capsule can inhibit autophagy and improve brain neurons lesion of CIRI rats, the mechanism may be related to regulate the expression of Beclin1 and LC3 in PI3K/Akt/Beclin1 signaling pathway.

An overview on dry eye disease diagnosis: options for new non-invasive testing technologies / 国际眼科杂志(Guoji Yanke Zazhi)

@#This literature review intends to provide an overview of the new non-invasive testing technologies and their role in the diagnosis of dry eye disease(DED). Including imaging technologies of tear volume, tear film stability, meibomian glands morphology and function, corneal morphology, biomarkers and ocular surface temperature, as well as tear osmolarity, optical quality, blinking test and so on. New testing technologies can provide an indirect and objective assessment of the ocular surface, tear condition and visual quality. Testing technologies, such as tear volume, meibography and tear osmolarity have been widely recognized and applied in clinical practice, showing higher specificity and sensitivity than traditional tests. Others, such as strip meniscometry, interferometer, light scattering technology, double-pass system, blinking test and so on, are currently in the stage of clinical research and improvement, and may translate to routine clinical detection techniques in the future. The new non-invasive testing technologies can non-invasively evaluate the ocular surface and tears, and measure the changes of components related to the disease, which play an important role in the diagnosis, classification, clinical management and curative effect evaluation of DED.

Repairing of composite soft tissue defects in limbs with micro-dissected chimeric perforator flap pedicled with the descending branch of lateral circumflex femoral artery / 中华显微外科杂志

Objective:To evaluate the feasibility and clinical results of micro-dissected chimeric (II-MCh) perforator flap based on the descending branch of lateral circumflex femoral artery(d-LCFA) for repairing composite soft tissue defects of limbs.Methods:From April, 2011 to December, 2019, a total of 19 cases of composite soft tissue defects of limbs combined with deep cavity were repaired with II-MCh perforator flap or micro-dissected thin lobulated (III-MPCh) perforator flap based on d-LCFA. The flap was micro-dissected before cut off the perforator. The deep dead cavity was filled with muscle flap, and the superficial wound was repaired with micro-dissected thin perforator flap. The sizes of flaps were 6.0 cm×3.0 cm-33.0 cm×8.0 cm. The muscle flaps were cut with volumes of 5.0 cm×3.0 cm×1.0 cm-13.0 cm×10.0 cm×1.5 cm. Donor sites of the flap were closed directly. Postoperative reviews were assigned at 1, 3, 6, 9 and 12 months. The appearance, colour, texture and recurrence of infection of the flap were checked and recorded.Results:Sixteen flaps survived successfully without necrosis and with primary healing at the donor sites. Two flaps had venous occlusion within 24 hours after surgery and healed after surgical exploration and venous anastomosis. One flap had arterial crisis within 24 hours after surgery and healed after surgical exploration and arterial anastomosis. All patients entered follow-up for 8-36 months with an average of 16 months. All recipient sites achieved satisfactory appearance and function, and only linear scars left at the donor sites.Conclusion:The II-MCh perforator flap based on d-LCFA is a special modality of anterolateral thigh perforator flap, which achieves a satisfying appearance at the recipient site by micro-dissecting the flap within one procedure. This emerging technique can effectively fill the dead cavity, and is an effective method to repair complex soft tissue defects of limbs combined with deep cavity.

The anti-neoplastic activities of aloperine in HeLa cervical cancer cells are associated with inhibition of the IL-6-JAK1-STAT3 feedback loop / 中国天然药物

Cervical cancer (CC) is recognized as the most common neoplasm in the female reproductive system worldwide. The lack of chemotherapeutic agents with outstanding effectiveness and safety severely compromises the anti-cipated prognosis of patients. Aloperine (ALO) is a natural quinolizidine alkaloid with marked anti-cancer effects on multiple malignancies as well as favorable activity in relieving inflammation, allergies and infection. However, its therapeutic efficacy and underlying mechanism in CC are still unclear. In the current study, MTT assay was employed to evaluate the viability of HeLa cells exposed to ALO to preliminarily estimate the effectiveness of ALO in CC. Then, the effects of ALO on the proliferation and apoptosis of HeLa cells were further investigated by plate colony formation and flow cytometry, respectively, while the migration and invasion of ALO-treated HeLa cells were evaluated using Transwell assay. Moreover, nude mice were subcutaneously inoculated with HeLa cells to demonstrate the anti-CC properties of ALO in vivo. The molecular mechanisms underlying these effects of ALO were evaluated by Western blot and immunohistochemical analysis. This study experimentally demonstrated that ALO inhibited the proliferation of HeLa cells via G2 phase cell cycle arrest. Simultaneously, ALO promoted an increase in the percentage of apoptotic HeLa cells by increasing the Bax/Bcl-2 ratio. Additionally, the migration and invasion of HeLa cells were attenuated by ALO treatment, which was considered to result from inhibition of epithelial-to-mesenchymal transition. For molecular mechanisms, the expression and activation of the IL-6-JAK1-STAT3 feedback loop were markedly suppressed by ALO treatment. This study indicated that ALO markedly suppresses the proliferation, migration and invasion and enhances the apoptosis of HeLa cells. In addition, these prominent anti-CC properties of ALO are associated with repression of the IL-6-JAK1-STAT3 feedback loop.

Anterolateral thigh chimeric perforator flap for repairing of large area compound tissue defect around knee joint / 中华显微外科杂志

Objective:To investigate the feasibility and clinical efficacy of anterolateral thigh chimeric perforator flap in repair of large area soft tissue defects around the knee joint.Methods:From January, 2015 to October, 2019, 9 patients with large area soft tissue defects around the knee joint were treated. All patients had different degrees of defect in knee joint capsule and joint opening. Before operation, the width of the flap was determined by "skin lifting and kneading test", and the location of perforators in anterolateral femoral region was confirmed and marked with the assistance of HHD detector. According to the size and shape of the wound surface, single leaf or lobulated perforator flap was designed based on the principle that the donor site should be closed directly. The minimum size of the flap was 14.0 cm×5.0 cm, there was 1 case of lobulated flap with the largest area, respectively was 17.0 cm×9.0 cm and 18.0 cm×8.5 cm. The chimeric tissue flap(muscle flap or fascia lata flap) was taken according to the location and severity of joint opening. The grafted tissue flap was used to fill the articular cavity, the flap was used to repair the wound of knee joint, the blood supply of the flap was reconstructed, and a drainage catheter was placed in the cavity of knee joint. The recovery follow-up conducted in outpatient department.Results:All flaps survived without vascular incident. The recipient site of flap in 1 patient was not thoroughly washed and drained, and there was more exudation. After dressing change and drainage, the rest recipient areas of the flap were healed in stage I. All patients entered 3 to 36(average 12) months of follow-up. The appearance and function of recipient area recovery were satisfactorily. Only a linear scar remained in donor site.Conclusion:Anterolateral thigh chemeric perforator flap is ideal for repairing large soft tissue defects around the knee joint.