Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

ObjectiveThe scale of microalgae farming industry is huge. During farming, it is easy for microalgae to be affected by miscellaneous bacteria and other contaminants. Because of that, periodic test is necessary to ensure the growth of microalgae. Present microscopy imaging and spectral analysis methods have higher requirements for experiment personnel, equipment and sites, for which it is unable to achieve real-time portable detection. For the purpose of real-time portable microalgae detection, a real-time microalgae detection system of low detection requirement and fast detection speed is needed. MethodsThis study has developed a microalgae detection system based on deep learning. A microscopy imaging device based on bright field was constructed. With imaged captured from the device, a neural network based on YOLOv3 was trained and deployed on microcomputer, thus realizing real-time portable microalgae detection. This study has also improved the feature extraction network by introducing cross-region residual connection and attention mechanism and replacing optimizer with Adam optimizer using multistage and multimethod strategy. ResultsWith cross-region residual connection, the mAP value reached 0.92. Compared with manual result, the detection error was 2.47%. ConclusionThe system could achieve real-time portable microalgae detection and provide relatively accurate detection result, so it can be applied to periodic test in microalgae farming.

In the past 37 years, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has undergone various major transmission routes in China, with the world most complex co-circulating HIV-1 subtypes, even the prevalence is still low. In response to the first epidemic outbreak of HIV in injecting drug users and the second one by illegal commercial blood collection, China issued the Anti-Drug Law and launched the Blood Donation Act and nationwide nucleic acid testing, which has avoided 98,232 to 211,200 estimated infections and almost ended the blood product-related infection. China has been providing free antiretroviral therapy (ART) since 2003, which covered >80% of the identified patients and achieved a viral suppression rate of 91%. To bend the curve of increasing the disease burden of HIV and finally end the epidemic, China should consider constraining HIV spread through sexual transmission, narrowing the gaps in identifying HIV cases, and the long-term effectiveness and safety of ART in the future.
Acquired Immunodeficiency Syndrome/prevention & control* ; China/epidemiology* ; Disease Outbreaks ; HIV Infections/prevention & control* ; Humans ; Prevalence

BACKGROUND: Human immunodeficiency virus (HIV) prevalence among student men who have sex with men (MSM) in college is more than 5.0% and keeps on increasing in China. This study aims to clarify the proportion of HIV recent infection, its propeller and the source among college student MSM. METHODS: We conducted a multicenter cross-sectional study in seven major Chinese cities during 2012-2013. HIV recent infections (≤ 168 days) and incidence was measured and estimated by BED HIV-1 capture enzyme immunoassay (BED-CEIA) testing strategy. HIV-related behaviors and transmitted drug resistance (TDR) were investigated and compared between the college student MSM, <25-year-old non-student youth MSM (NSYM), and ≥25-year-old non-student non-youth MSM (NSNYM), using structured survey, and analyses of drug resistance. RESULTS: Overall, 4,496 (4496/4526, 99.3%) were eligible for enrollment, comprising 565 college student MSM, 1,094 NSYM, and 2,837 NSNYM. The proportion of HIV recent infection were 70.3% (26/37), 50.8% (65/128) and 35.1% (95/271), the HIV incidence rate were 10.0 (95% CI: 6.2-13.9)/100PY, 12.9 (95% CI: 9.8-16.1)/100PY, 6.8 (95% CI: 5.4-8.2)/100PY, and TDR prevalence were 7.4% (2/27), 2.0%, (2/98) and 4.9% (11/226), among student MSM, NSYM, and NSNYM, respectively. Among HIV positive student MSM with age< 21-year-old, the proportion of HIV recent infection is 90.9% (10/11). Factors independently associated with HIV recent infection in student MSM was usage of recreational drug in the past 6 months (AOR: 2.5; 95% CI: 1.0-5.8). CONCLUSIONS College student MSM had higher proportion of HIV recent infection and TDR than the youth and older MSM in China during 2012-2013. The HIV infections were more likely to happen during the early year of college life among student MSM.
Adolescent ; Adult ; Aged ; China/epidemiology* ; Cities ; Cross-Sectional Studies ; Drug Resistance ; HIV Infections/epidemiology* ; Homosexuality, Male ; Humans ; Incidence ; Male ; Prevalence ; Risk Factors ; Sexual Behavior ; Sexual and Gender Minorities ; Students ; Young Adult

Objective: To investigate the effect of Trichosanthis Pericarpium aqueous extract(TPAE)in protecting H9c2 cells from hypoxia/reoxygenation (H/R) injury by activating phosphatidylionsitol-3-kinase/protein kinase B/nitric oxide(PI3K/Akt/NO) signaling pathway. Method: The 2.5 mmol·L^-1 Na₂S₂O₄ was used to induce the model of H9c2 cardiomyocytes H/R injury in the experiments. The cultured H9c2 cardiomyocytes were randomly divided into normal group, H/R group (model group) and inhibition group (LY294002, 10 μmol·L^-1). In the H/R + TPAE group, 50 mg·L^-1 TPAE was added to the cultures at 24 h before H/R exposure. Cell viability was measured by methyl thiazolyl tetrazolium (MTT) assay. The amounts of NO, endothelial nitric oxide synthase (eNOS), and induced nitric oxide synthase (iNOS) were tested by enzyme linked immunosorbent assay (ELISA) kits. Reverse transcription-quantitative real-time polymerase chain reaction (Real-time PCR) was performed to analyze relative mRNA expressions of Akt, eNOS and iNOS. Western blot was used to detect the expressions of Akt, p-Akt (Ser 473), eNOS, and iNOS. Result: Compared with the normal control group,the cell viability significantly decreased in the model control group (P<0.01), the release of NO was obviously down-regulated (P<0.01), the mRNA and protein expressions of p-Akt, Akt, eNOS were remarkably decreased (P<0.01), while those of iNOS were up-regulated (P<0.01). Compared with the H/R group,the pretreatment with TPAE remarkably improved the morphological lesion of cardiomyocytes, enhanced cell viability(P<0.01),increased the expressions of Akt, p-Akt (Ser 473) and eNOS(P<0.01),decreased the expression of iNOS(P<0.01), and increased the release of NO(P<0.01). The PI3K inhibitor LY294002 was used. Obviously, cardioprotection of Trichosanthis Pericarpium aqueous extract was blocked by co-treatment LY294002, and cell viability was correspondingly reversed. Conclusion: TPAE can protect H9c2 cardiomyocytes from H/R injury by activating PI3K/Akt signaling pathway,which might be related to the up-regulation of the mRNA and protein expressions of eNOS, the down-regulation of the level of iNOS, and the increase of the production of physiological amounts of NO.

OBJECTIVE To investigate the protective effect and mechanisms of luteolin-7-O-β-d-glucuronide (LGU) on oxygen glucose deprivation (OGD)-induced H9C2 cardiomyocytes injury. METH-ODS The protective effect of LGU on OGD-induced H9C2 cardiomyocytes death were investigated by MTT assay. The microfilament change of H9C2 cardiomyocytes was detected by phalloidin staining and the lactate dehydrogenase (LDH) leakage rate was also detected by LDH kit. In order to explore the possible mechanisms of LGU, ATP content, intracellular Ca2+fluorescent intensity and concentra-tion, mitochondrial membrane potential (MMP)and the expressions of apoptosis-related proteins were detected by ATP kit,CLSM(Fluo-3/AM probe),Ca2+kit,CLSM(JC-1 probe)and western blotting meth-od, respectively. RESULTS The inhibition of H9C2 cardiomyocyte survival rate inducedby OGD was improvedby pretreated with LGU in a concentrationdependent manner. The microfilaments injury as well as the increase of LDH leakage rate were also improvedby pretreated with LGU.The ATP content was significantly decreased,intracellular Ca2+fluorescent intensity and concentration were significantly increased and the MMP was significantly decreased 4 hafter OGD. LGU significantly reversed the de-crease of intracellular ATP content,the increase of Ca2+fluorescent intensity and concentration and the decrease of MMP.The release of cytochrome C,the expressionsof caspase-9 and caspase-3 in H9C2 cardiomyocytes were increased 16 h after OGD.LGUsignificantly inhibited the changes of these apop-tosis-related proteins. CONCLUSION LGU has a significant protective effect against OGD-induced H9C2 cardiomyocytes injury through inhibiting calcium overload,increasing ATP content,improving mi-tochondrial function and inhibiting apoptosis.

BACKGROUNDSome problems have been found in the usually adopted combined approach for the removal of intra-extracranial tumors in skull base. Herein, we described a pure endoscopic transnasal or transoral approach (ETA) for the removal of intra-extracranial tumors in various skull base regions.

METHODSRetrospectively, clinical data, major surgical complications, pre- and postoperative images, and follow-up information of a series of 85 patients with intra-extracranial tumors in various skull base regions who were treated by surgery via ETA in our skull base center during the past 10 years were reviewed and analyzed.

RESULTSGross total tumor removal was achieved in 80/85 cases (94.1%) in this study. All 37 cases with tumors in anterior skull base and all 14 cases with tumors in jugular foramen received total tumor removal. Thirteen and three cases with tumors in clivus received total and subtotal tumor removal, respectively. Total and subtotal tumor removal was performed for 16 cases and 2 cases in lateral skull base, respectively. The complications in this study included: cerebrospinal fluid leakage (n = 3), meningitis (n = 3), and new cranial nerve deficits (n = 3; recovered in 3 months after surgery). In the follow-up period of 40-151 months (median: 77 months), seven patients (8.8%) out of the 80 cases of total tumor removal experienced recurrence.

CONCLUSIONSComplete resection of intra-extracranial growing tumors in various skull base regions can be achieved via the pure ETA in one stage in selected cases. Surgical procedure for radical removal of tumors is feasible and safe.

Objective To investigate the therapeutic effect of interleukin-2(IL-2)on experimental autoimmune encephalomyelitis(EAE)mice.Methods After establishment of the EAE(experimental autoimmune encephalomyelitis) mouse models with MOG35-55 polypeptides,the mice were grouped according to the neurological function score and divided into control group,EAE group and low dose IL-2 treatment group.A double blind method was used to evaluate the neuro-logical impairment in mice.On the 29th day,pathological experiments were carried out in the mice's brain and spinal cord, hematoxylin-eosin staining was used to evaluate the scoring of inflammatory cell infiltration and luxol fast blue staining was used to evaluate the scoring of demyelinating.The proportion of regulatory T cells(Treg)and NK cells(natural killer cell, NK)was detected by flow cytometry,and the immunohistochemical method was used to detect the expressions of glial fibril -lary acidic protein(GFAP)and myelin basic protein(MBP)in the spinal cord.Results Compared with the EAE group, the neurological function score, the inflammatory cell infiltration score and the demyelinating score of the low dose IL-2 treatment group were reduced.The proportion of Treg cells in the low dose IL-2 treatment group was significantly higher than that in the EAE group,and the proportion of NK cells in the low dose IL-2 treatment group was slightly higher than that in the EAE group The expression of GFAP and MBP was detected by immunohistochemistry.The expression level of GFAP in low dose IL-2 treatment group was significantly lower than that in the EAE group,while the expression level of MBP was higher than that in the EAE group.Conclusion Low dose IL-2 has significant therapeutic effect on EAE mice.

OBJECTIVETo study the toxicity features of high glucose on the endothelial cell cycle and the influence of Dan Gua-Fang, a Chinese herbal compound prescription, on the reproductive cycle of vascular endothelial cells cultivated under a high glucose condition; to reveal the partial mechanisms of Dan Gua-Fang in the prevention and treatment of endothelial injury caused by hyperglycemia in diabetes mellitus (DM); and offer a reference for dealing with the vascular complications of DM patients with long-term high blood glucose.

METHODSBased on the previous 3-(4,5)-dimethylthiahiazo (z-y1)-3-5-diphenytetrazoliumromide (MTT) experiment, under different medium concentrations of glucose and Dangua liquor, the endothelial cells of vein-304 (ECV-304) were divided into 6 groups as follows: standard culture group (Group A, 5.56 mmol/L glucose); 1/300 herb-standard group (Group B); high glucose culture group (Group C, 16.67 mmol/L glucose); 1/150 herb-high glucose group (Group D); 1/300 herb-high glucose group (Group E); and 1/600 herb-high glucose group (Group F). The cell cycle was assayed using flow cytometry after cells were cultivated for 36, 72 and 108 h, respectively.

RESULTS(1) The percentage of cells in the G0/G1 phase was significantly increased in Group C compared with that in Group A (P<0.05), while the percentage of S-phase (S%) cells in Group C was significantly reduced compared with Group A (P<0.05); the latter difference was dynamically related to the length of growing time of the endothelial cells in a high glucose environment. (2) The S% cells in Group A was decreased by 30.25% (from 40.23% to 28.06%) from 36 h to 72 h, and 12.33% (from 28.06% to 24.60%) from 72 h to 108 h; while in Group C, the corresponding decreases were 23.05% and 21.87%, respectively. The difference of S% cells between the two groups reached statistical significance at 108 h (P<0.05). (3) The percentage difference of cells in the G2/M phase between Group C and Group A was statistically significant at 72 h (P<0.01). (4) 1/300 Dan Gua-Fang completely reversed the harmful effect caused by 16.67 mmol/L high glucose on the cell cycle; moreover it did not disturb the cell cycle when the cell was cultivated in a glucose concentration of 5.56 mmol/L.

CONCLUSIONSHigh glucose produces an independent impact on the cell cycle. Persistent blocking of the cell cycle and its arrest at the G0/G1 phase are toxic effects of high glucose on the endothelial cell cycle. The corresponding variation of the arrest appears in the S phase. 1/300 Dan Gua-Fang completely eliminates the blockage of high glucose on the endothelial cell cycle.

Cell Cycle ; drug effects ; physiology ; Cells, Cultured ; Culture Media ; pharmacology ; Cytoprotection ; drug effects ; Dose-Response Relationship, Drug ; Drug Evaluation, Preclinical ; Drugs, Chinese Herbal ; pharmacology ; Endothelial Cells ; drug effects ; physiology ; Flow Cytometry ; Glucose ; adverse effects ; Humans

OBJECTIVETo study the clinical effects of Achillon for the treatment of acute Achilles tendon rupture (AATR).

METHODSFrom April 2009 to April 2010, 19 patients with AATR who were treated with Achillon were retrospectively analyzed. There were 17 males and 2 females, with an average age of 40.2 years (30 to 58 years). There were 9 cases of sports injury, and 2 case of fall injury. The time from injury to surgery ranged from 0 to 8 days (2.2 days on average). The results of Thompson test and single heel rise test were positive in 19 cases. Clinical data were assessed with the patient satisfaction and the AOFAS hindfoot score during follow-up.

RESULTSAll the patients were followed up, and the duration ranged from 12 to 28 months (19.9 months on average). The average operation time was 41 minutes. There were no wound infections, recurrent rupture, or sural nerve complications. At the latest follow-up, 18 patients were totally satisfied with the surgical result, 1 patient feel generally due to mild pain when running. None of the patients were dissatisfied with the final results the latest follow-up. At the latest follow-up, the AOFAS score was 98.42 +/- 3.29 (89 to 100). All the patients regained normal range of motion and were able to resume their previous activities at six months after operation, with a high rate of satisfaction. Average decreased of mid-calf circumference was (0.82 +/- 0.85) cm (ranged from 0 to 3 cm).

CONCLUSIONTreatment with Achillon is safe, effective for AATR with low incidence of complications and early active rehabilitation can be carried out. It is a good method to treat AATR.

Achilles Tendon ; injuries ; surgery ; Acute Disease ; Adult ; Female ; Humans ; Male ; Middle Aged ; Minimally Invasive Surgical Procedures ; instrumentation ; Retrospective Studies ; Rupture ; Suture Techniques ; instrumentation ; Tendon Injuries ; surgery