The Masquelet technique, also known as the induced membrane technique, is a surgical technique for repairing large bone defects based on the use of a membrane generated by a foreign body reaction for bone grafting. This technique is not only simple to perform, with few complications and quick recovery, but also has excellent clinical results. To better understand the mechanisms by which this technique promotes bone defect repair and the factors that require special attention in practice, we examined and summarized the relevant research advances in this technique by searching, reading, and analysing the literature. Literature show that the Masquelet technique may promote the repair of bone defects through the physical septum and molecular barrier, vascular network, enrichment of mesenchymal stem cells, and high expression of bone-related growth factors, and the repair process is affected by the properties of spacers, the timing of bone graft, mechanical environment, intramembrane filling materials, artificial membrane, and pharmaceutical/biological agents/physical stimulation.
Humans ; Bone Transplantation/methods* ; Membranes, Artificial ; Bone Regeneration ; Animals

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) have recently been identified to be closely related to the occurrence and development of atherosclerosis (AS). A growing body of evidence has suggested Chinese medicine takes unique advantages in preventing and treating AS. In this review, the related research progress of AS and LOX-1 has been summarized. And the anti-AS effects of 10 active components of herbal medicine through LOX-1 regulation have been further reviewed. As a potential biomarker and target for intervention in AS, LOX-1 targeted therapy might provide a promising and novel approach to atherosclerotic prevention and treatment.
Humans ; Atherosclerosis ; Scavenger Receptors, Class E/physiology* ; Biomarkers ; Plant Extracts ; Lipoproteins, LDL

ObjectiveTo investigate the causes of discontinuation of subcutaneous allergen immunotherapy （SCIT） in patients with allergic rhinitis （AR） and / or bronchial asthma （BA） in the Pearl River Delta region， and to improve the compliance of these patients. MethodsIt was a retrospective， multi-center real world study. Patients with AR and / or BA receiving SCIT in six hospitals in the Pearl River Delta region from January 2015 to December 2020 were recruited. The clinical data of all patients were collected， and the patients with abscission were followed up by telephone. ResultsIn this study， 1 244 patients who received SCIT were included. A total of 427 patients stopped SCIT before 3 years （34.3%）. Children， married patients and patients with positive family history of allergy and total immunoglobulin E （tIgE） > 200 U / mL showed relatively good compliance （P<0.05）， while more patients of AR alone stopped SCIT before 3 years than patients of AR complicated with BA （P<0.05）. Patients with high symptom score and drug score before treatment had better compliance （P<0.001）. A total of 279 cases （65.3%） of the non-adherence group were followed by telephone. The first three reasons for discontinuing treatment were the treatment did not achieve the expected effect （115 cases， 41.2%）， factors pertaining to learning and daily life （74 cases， 26.5%） and adverse reactions （29 cases， 10.4%）. The number of patients stopping SCIT decreased gradually with time； the proportion of patients who discontinued treatment due to adverse reactions in the first year of treatment was higher than that in the second and third years （P<0.05）. ConclusionFailure to achieve the expected effect was the primary reason for poor compliance of patients receiving SCIT and discontinuation mainly occurred on the early stage of the treatment. The supervision from family members is helpful to improve the compliance， suggesting that individualized measures need to be taken to reduce the loss of SCIT.

OBJECTIVE: To investigate the therapeutic effect of Yixin Ningshen Tablet (YXNS) on comorbidity of myocardial infarction (MI) and depression in rats and explore the underlying mechanism. METHODS: The Sprague-Dawley rats were randomly divided into 5 groups with 7 rats in each group according to their weights, including control, model, fluoxetine (FLXT, 10 mg/kg), low-dose YXNS (LYXNS, 100 mg/kg), and high-dose YXNS (HYXNS, 300 mg/kg) groups. All rats were pretreated with corresponding drugs for 12 weeks. The rat model of MI and depression was constructed by ligation of left anterior descending coronary artery and chronic mild stress stimulation. The echocardiography, sucrose preference test, open field test, and forced swim test were performed. Myocardial infarction (MI) area and myocardial apoptosis was also detected. Serum levels of interleukin (IL)-6, IL-1β, tumor necrosis factor-α (TNF-α), 5-hydroxytryptamine (5-HT), adrenocorticotrophic hormone (ACTH), corticosterone (CORT), and norepinephrine (NE) were determined by enzyme linked immunosorbent assay. The proteins of adenosine 5'-monophosphate -activated protein kinase (AMPK), p-AMPK, peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), and nuclear respiratory factor 1 (NRF1) in heart were detected by Western blot analysis. The expression levels of TNF-α, IL-6, indoleamine 2,3-dioxygenase (IDO1), kynurenine 3-monooxygenase (KMO), and kynureninase (KYNU) in hippocampus were detected by real-time quantitative polymerase chain reaction. RESULTS: Compared with the model group, the cardiac function of rats treated with YXNS improved significantly (P<0.01). Meanwhile, YXNS effectively reduced MI size and cardiomyocytes apoptosis of rats (P<0.01 or P<0.05), promoted AMPK phosphorylation, and increased PGC-1α protein expression (P<0.01 or P<0.05). HYXNS significantly increased locomotor activity of rats, decreased the levels of TNF-α, IL-6 and IL-1β, and increased the serum levels of 5-HT, NE, ACTH, and CORT (all P<0.05). Moreover, HYXNS decreased the mRNA expressions of IDO1, KMO and KYNU (P<0.05). CONCLUSIONS YXNS can relieve MI by enhancing myocardial energy metabolism. Meanwhile, YXNS can alleviate depression by resisting inflammation and increasing availability of monoamine neurotransmitters. It may be used as a potential drug to treat comorbidity of MI and depression.
AMP-Activated Protein Kinases/metabolism* ; Adrenocorticotropic Hormone ; Animals ; Comorbidity ; Depression/drug therapy* ; Energy Metabolism ; Interleukin-6/metabolism* ; Myocardial Infarction/pathology* ; Neurotransmitter Agents ; Rats ; Rats, Sprague-Dawley ; Serotonin/metabolism* ; Tablets ; Tumor Necrosis Factor-alpha/metabolism*

Objective:To investigate the effect of total ginsenoside ginseng root on the learning and memory impairment and anxiety of hindlimb suspension rats by detecting the performance of rats in the water maze， elevated plus maze， and the expression of hypothalamic-pituitary-adrenal （HPA） axis， inflammatory factors and tryptophan pathway related factors through the intervention of ginsenosides in hindlimb suspension rats. Method:The Wistar male rats were divided into normal group， hindlimb suspension model group， Huperzine A group （0.1 mg·kg^-1）， and total ginsenoside ginseng root low and high dose groups （100， 200 mg·kg^-1）， with 8 rats in each group. Except for the normal group， the rats in the other groups maintained a -30° hindlimb suspension state for 24 h. The normal group and the model group received intragastric administration of 10 mL·kg^-1 pure water . After 28 days of continuous administration， the water maze and elevated plus maze behavioral tests were performed. After the tests， blood was taken from the abdominal aorta， and the rat brain cortex was peeled off on ice， quenched with liquid nitrogen， and stored at -80 ℃ for later use. LC-MS/MS was used to detect neurotransmitter levels of dopamine， acetylcholine， glutamate， γ-aminobutyric acid and tryptophan pathway metabolites （tryptophan， 5-hydroxytryptamine， 5-hydroxyindoleacetic acid， kynurenine， 3-hydroxykynurenine， and kynurenine） in rat brain cortex. An enzyme-linked immunosorbent assay （ELISA） kit was used to detect the levels of inflammatory factors interleukin-6 （IL-6）， interleukin-10 （IL-10， the HPA axis-related hormone corticotropin （ACTH）， and the level of corticosterone （CORT）. Result:Compared with the normal group， the escape latency in the water maze significantly increased， the number of crossings was significantly reduced， and the number of open-arm entry and the percentage of open-arm entry were significantly reduced in the elevated plus maze in model group （P<0.05， P<0.01）， the content of dopamine， acetylcholine， glutamic acid， and γ-aminobutyric acid in the cortex decreased， kynurenine and kynurenic acid showed an upward trend， 3-hydroxykynurenine， 5-hydroxytryptamine， 5-hydroxyindole acetic acid showed a downward trend， and the levels of IL-6， IL-10， ACTH， and CORT in the serum significantly increased （P<0.05， P<0.01）. Compared with the model group of rats， total ginsenoside ginseng root low and high dose groups group reduced the avoidance latency in the water maze， and increased the number of crossings and the number of open arms of the elevated plus maze， dopamine， acetylcholine， glutamate， and γ-aminobutyl content increased， while kynurenine and kynurenic acid showed a downward trend， 3-hydroxykynurenine， serotonin， and 5-hydroxyindole acetic acid showed an upward trend， and IL-6， IL-10， ACTH， and CORT factor levels were down-regulated（P<0.05， P<0.01）. Conclusion:Hindlimb suspension for 28 days in simulated microgravity can impair the learning and memory ability of rats and cause anxiety-like behaviors. Total ginsenoside ginseng root can improve their learning and memory impairment and anxiety-like behaviors. The mechanism may be mainly related to inhibiting body inflammation and regulating HPA axis imbalance.

COVID-19 has swept globally and Pakistan is no exception.To investigate the initial introductions and transmissions of the SARS-CoV-2 in Pakistan,we performed the largest genomic epidemiology study of COVID-19 in Pakistan and generated 150 complete SARS-CoV-2 genome sequences from samples collected from March 16 to June 1,2020.We identified a total of 347 mutated positions,31 of which were over-represented in Pakistan.Meanwhile,we found over 1000 intra-host single-nucleotide variants(iSNVs).Several of them occurred concurrently,indicating possible interactions among them or coevolution.Some of the high-frequency iSNVs in Pakistan were not observed in the global population,suggesting strong purifying selections.The genomic epidemiology revealed five distinctive spreading clusters.The largest cluster consisted of 74 viruses which were derived from different geographic locations of Pakistan and formed a deep hierarchical structure,indicating an extensive and persistent nation-wide transmission of the virus that was probably attributed to a signature mutation(G8371T in ORF 1ab)of this cluster.Further-more,28 putative international introductions were identified,several of which are consistent with the epidemiological investigations.In all,this study has inferred the possible pathways of introduc-tions and transmissions of SARS-CoV-2 in Pakistan,which could aid ongoing and future viral surveillance and COVID-19 control.

Objective:From a new perspective，to explore therapeutic effect of Huidouba (HDB) on alleviating kidney oxidative damage in rats with diabetic nephropathy (DN) and provide a scientific basis for developing HDB as a potential Tibetan medicine for treatment of DN. Method:Rats were fed with high-fat diet (HFD) and injected with streptozocin (STZ, 65 mg·kg^-1) intraperitoneally to induce DN model, while rats in Blank group were injected with an equal volume of vehicle and fed with normal chow. The successfully modeling DN rats were randomly divided into three groups, 8 rats per group, DN model group (10 mL·kg^-1·d^-1), Metformin group (0.045 g·kg^-1·d^-1) and HDB group (0.18 g·kg^-1·d^-1). Monitor body weight (BW) and fasting blood glucose (FBG) weekly, and collect 24 hours urine before and after medication to examine microalbuminuria (mAlb). Calculate kidney index (KI) after sacrificing, analyze mAlb, serum creatinine (SCr) and blood urea nitrogen (BUN) with a fully automatic biochemical analyzer. Histopathology of kidney was observed by Masson staining. Lipid peroxidation malondialdehyde (MDA) assay kit was used to examine MDA content in kidney tissue. Nox4, as a subtype of triphosphopyridine nucleotide (NADPH) oxidase family was determined by Western blot and immunofluorescence assay of kidney tissue. Result:Compared with blank group, levels of FBG, 24 h mAlb, SCr, BUN and MDA in DN model group were increased (P<0.01), tissue damage was obvious and Nox4 expression in glumeruli was increased significantly (P<0.01). Compared with DN model group, levels of FBG, 24 h mAlb, SCr, BUN and MDA in drug administration groups were decreased (P<0.01), kidney injury was alleviated and Nox4 expression was down-regulated（P<0.01）. Conclusion:HDB as a Yiqiyangyin Tibetan medicine, could ease oxidative stress injury of kidney and reduce proteinuria in DN rats, thus prevent the development of DN. Its mechanism is closely related to down-regulating Nox4 expression of kidney tissue in DN rats.