The immune response against infection is a multifaceted process encompassing the activation and migration of diverse immune cells, as well as the clearance of pathogens. The behaviors of immune cells and the identification of pathogens play pivotal roles as indicators for disease diagnosis and prediction. In recent years, the utilization of microfluidic chip technology has gained substantial attention within the areas of biology, pharmacology, and clinical research and diagnosis. This is primarily attributed to the numerous advantages it offers, including miniaturization, enhanced throughput, heightened sensitivity, expedited analysis, and reduced sample consumption. As a result, microfluidic technology has facilitated the development and utilization of immune cell behavioral assays, bacterial growth studies, and drug-screening assays. This paper is to review the application of microfluidic technology in the field of anti-infection immunity research, focusing on the analysis of migratory behavior of innate immune cells, deformation of their nuclei, and rapid identification of pathogenic bacteria and viruses. The primary objective of this review is to advance the application of microfluidic technology in research on both anti-infection immunity and clinical diagnosis.

Cognitive reserve referred to the cumulative flexibility of an individual's cognitive processes,whereas accurately assessing an individual's cognitive reserve and intervening was important for preventing the occurrence of cognitive dysfunction as well as promoting cognitive health.This article reviewed the main contents and applications of cognitive reserve assessment tools,and compared the characteristics and limitations of each assessment tool.The purpose was to provide ideas for the development of cognitive reserve assessment tools suitable for China's cultural background and population characteristics,and to provide a basis for accurately assessing the current status of China's cognitive reserve and formulating targeted cognitive reserve enhancement programs.

This paper summarized Professor PENG Peichu's experience in the differentiation and treatment of prostate cancer in three phases and four stages. It is considered that prostatic cancer is categorized into root deficiency and branch excess， with depletion of healthy qi as the root， and the accumulation of cancer toxin as the minifestation. Clinical diagnosis and treatment of prostatic cancer can be divided into three phases and four stages according to the exuberance and decline of pathogenic and healthy qi and the changes of deficiency and excess of yin and yang. In the initial accumulation phase of cancer toxin （yang excess stage）， the key pathogenesis is the accumulation of dampness， heat and static blood， and internal generation of cancer toxin， and the treatment should be resolving toxins， fighting cancer and dispelling yang excess. In the phase of healthy qi deficiency and toxin accumulation （yin deficiency stage）， with the lung and kidney yin deficiency， dampness， heat and static toxin accumulation as the key pathogenesis， the treatment should be centered on mutual generation between metal and water to nourish kidney yin， supplemented with the method of clearing heat and draining dampness， activating blood and resolving toxins， for which self-made Nanbei Formula（南北方）is usually used. In the phase of yang deficiency and cold stagnation （yang deficiency stage and yin excess stage）， with the spleen and kidney yang deficiency， cold dampness stagnation， static heat and toxin accumulation as the key pathogenesis， the treatment should be warming and tonifying spleen and kidney to dissipate cold accumulation； for deficiency of both yin and yang， and excess pathogen obstruction， modified Yanghe Decoction（阳和汤） is recommended， while for yang deficiency， cold congealing and blood stasis， self-made Wenshen Sanjie Formula（温肾散结方） can be used， and for cold dampness binding with cancer toxin， and cold complex with heat， self-made Quanan Formula （泉安方） is advised.

Objective:To explore the effect of pentraxin 3 (PTX3) on memory improvement and Aβ expression in Alzheimer's disease (AD) model mice.Methods:(1) Ten 5-month-old 5×FAD mice were randomly divided into PTX3 group and model group ( n=5); 5 C57BL/6 wild-type mice at the same age were selected as control group; mice in the PTX3 group and control group were stereotactically injected 4 μL 0.5 g/L PTX3 or same dose of phosphate buffered saline (PBS); Morris water maze test was used to detect the learning and memory abilities, Y maze test was used to detect the short-term memory, and ELISA was used to obsevre the contents of Aβ 40 and Aβ 42 in the brain hemisphere. (2) Twenty-five 3-month-old 5×FAD mice were randomly divided into model group, 2 μg/kg PTX3 group, 4 μg/kg PTX3 group, 8 μg/kg PTX3 group, and 16 μg/kg PTX3 group ( n=5); 5 C57BL/6 wild-type mice at the same age were selected as control group; mice in the PTX3 groups were intranasally injected 2, 4, 8, and 16 μg/kg PTX3, respectively; those in the model group and control group were intranasally injected same dose of PBS; injection was given once every 96 h for a total of 7 times. Morris water maze test was used to detect the learning and memory abilities, Y maze test was used to detect the short-term memory, and ELISA was used to obsevre the contents of Aβ 40 and Aβ 42 in the hippocampus. Results:(1) Compared with the model group, the PTX3 group had significantly shorter platform latency, higher percentage of exploration time and higher percentage of spontaneous alternations ( P<0.05). Compared with those in model group ([63.38±21.42] pg/mL, [29.77±6.11] pg/mL), the concentrations of Aβ 40 and Aβ 42 in the brain tissues of PTX3 group ([15.87±2.11] pg/mL, [16.55±1.95] pg/mL) were statistically lower ( P<0.05). (2) Compared with the model group, the 16 μg/kg PTX3 group had significantly shorter escape latency and higher percentage of exploration time ( P<0.05); compared with the model group, the 2 μg/kg PTX3 group and 16 μg/kg PTX3 group had significantly higher percentage of spontaneous alternations ( P<0.05). The contents of Aβ 40 and Aβ 42 in the hippocampus of 8 μg/kg PTX3 group and 16 μg/kg PTX3 group were statistically lower compared with those in the model group ( P<0.05). Conclusion:PTX3 may attenuate cognitive deficits and decrease Aβ expression in the brain or hippocampus tissues of 5×FAD mice with AD.

METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell (mESC). While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-independent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification. Mechanistically, METTL14, but not METTL3, binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression. The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs. This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance, and differentiation of mESCs.
Animals ; Mice ; Methylation ; Chromatin ; Histones/metabolism* ; RNA, Messenger/genetics* ; Methyltransferases/metabolism* ; RNA/metabolism*

Objective:To investigate the role and possible pathogenesis of high mobility group protein B1 (HMGB1) in lipopolysaccharide (LPS)-induced acute lung injury/acute respiratory distress syndrome (ALI/ARDS).Methods:① In vivo, 24 SPFC57BL/6 male mice were randomly divided into normal control group, ALI/ARDS model group, ethyl pyruvate (EP) treatment group and EP control group, with 6 mice in each group. The ALI/ARDS model was established by intraperitoneal injection of 20 mg/kg LPS. Mice in normal control group and EP control group were intraperitoneally injected with the same amount of sterile normal saline. Then, mice in the EP treatment group and EP control group were intraperitoneally injected with 40 mg/kg HMGB1 inhibitor EP. After 6 hours, the mice were sacrificed and lung tissues were collected. The expressions of heparan sulfate (HS), syndecans-1 (SDC-1), heparanase (HPA) and matrix metalloproteinases-9 (MMP-9) in lung tissues were detected by immunofluorescence technique. Orbital blood of mice was collected and serum was extracted to detect the content of HMGB1 by enzyme linked immunosorbent assay (ELISA). ② In vitro, human umbilical vein endothelial cells (HUVECs) were randomly divided into 6 groups: normal control group, HUVECs damage group (treated with 1 mg/L LPS for 6 hours), HMGB1 group (treated with 1 μmol/L recombinant HMGB1 for 6 hours), HMGB1+EP group (treated with recombinant HMGB1 for 1 hour and then added 1 μmol/L EP for 6 hours), LPS+EP group (treated with LPS for 1 hour and then added 1 μmol/L EP for 6 hours), EP group (treated with 1 μmol/L EP for 6 hours). The expressions of HS, SDC-1, HPA and MMP-9 in endothelial cells were detected by immunofluorescence technique. Results:① In vivo, light microscopy showed that the alveolar space was thickened after LPS stimulation, and there were a large number of inflammatory cells infiltrating in the alveolar space. Compared with ALI/ARDS model group, the expressions of HS and SDC-1 in lung tissue of EP treatment group were significantly increased [HS (fluorescence intensity): 0.80±0.20 vs. 0.53±0.02, SDC-1 (fluorescence intensity): 0.72±0.02 vs. 0.51±0.01, both P < 0.05], and the expressions of HPA and MMP-9 were significantly decreased [HPA (fluorescence intensity): 2.36±0.05 vs. 3.00±0.04, MMP-9 (fluorescence intensity): 2.55±0.13 vs. 3.26±0.05, both P < 0.05]; there were no significant changes of the above indexes in EP control group. Compared with ALI/ARDS model group, the content of serum HMGB1 in EP treatment group decreased significantly (μg/L: 131.88±16.67 vs. 341.13±22.47, P < 0.05); there was no significant change in the EP control group. ② In vitro, compared with HMGB1 group, the expressions of HS and SDC-1 in HMGB1+EP group were significantly higher [HS (fluorescence intensity): 0.83±0.07 vs. 0.56±0.03, SDC-1 (fluorescence intensity): 0.80±0.01 vs. 0.61±0.01, both P < 0.05], and the expressions of HPA and MMP-9 were significantly lower [HPA (fluorescence intensity): 1.30±0.02 vs. 2.29±0.05, MMP-9 (fluorescence intensity): 1.55±0.04 vs. 2.50±0.06, both P < 0.05]; the expression of HS, SDC-1, HPA and MMP-9 had no significant changes in EP group. Conclusion:HMGB1 participates in LPS-induced injury of endothelial cell glycocalyx, leading to increased lung permeability, and inhibition of HMGB1 can alleviate lung injury.

Objective: To investigate the application and therapeutic effect of external tissue expansion-assisted autologous fat grafting for delayed breast reconstruction. Methods: Patients began wearing the BRAVA negative pressure system 8 hours a day for recipient tissue expansion for one month before the fat grafting procedure. After fat grafting, BRAVA was recommended to be worn 8 hours a day from postoperative 48 hours to one month. The interval of each fat grafting procedure was 2.5 to 3.0 months. The procedures were repeated until the completion of breast reconstruction. Water-jet assisted liposuction and subcutaneous release of scars were also performed during surgery. Results: From January 2013 to November 2016, 29 patients were followed up for 12 to 58 months, with average of 31.6 months. 28 patients completed the external tissue expansion-assisted autologous fat grafting breast reconstruction. Completion required 1 to 6 procedures, with average of 3.4 procedures. The total initial fat fill volume for each breast was ranged from 200 to 1 000 ml, with average of 583.7 ml. The initial fat fill volume for each breast was ranged from 92.5 to 243.7 ml per operation, with average of 173.8 ml. One patient underwent latissimus dorsi myocutaneous flap breast reconstruction after 3 fat grafting procedures. 8 patients completed the inframammary fold reconstruction, 3 patients underwent breast lift, 1 patient underwent lipofilling augmentation for the contralateral side. Postoperative satisfaction rate was 82.8% in patients and 75.9% in surgeon. Complication statistics: 5 cases of palpable nodules which recognized as fat necrosis (17.2%), one case of nontuberculous mycobacterial infection (3.4%) and one case of locoregional cancer recurrence (3.4%). Conclusions External tissue expansion-assisted autologous fat grafting is a minimally invasive procedure for breast reconstruction. Satisfactory results could be obtained for most of the patients who would like to choose fat grafting and have enough fat deposit in other parts of the body.

Objective To investigate the effects and mechanism of remifentanil on renal ischemia/reperfusion(IR) injury via mediating Fas apoptosis signal pathway in rats.Methods Sprague-Dawley rats were divided into 3 groups (n =20 each) by using the random number table method:sham operation group (S group),IR control group (IR group),experimental group (Rgroup).The renal IR model was prepared by clamping the bilateral renal arteries for 45 min followedby reperfusion in IR group and R group.In R group,remifentanil was infused at 1.0μg·kg-1 ·min-1 via the tail vein starting from 15 min before ischemia until 30 min of reperfusion.In S group and IR group,the same volume of physiological saline was given.At 15 min before ischemia and at 3 h,12 h,24 h of reperfusion,the renal tissue samples were obtained for detecting the apoptosis rate by flow cytometry,determining the level of Fas mRNA expression by RT-PCR,the level of caspase-8 and caspase-3 activation by Western blotting,and scoring the number of kidney tubules injury by Paller'method.Results In IR group,the renal tubular injury score,the apoptosis rate,the expression of Fas mRNA and the activation of caspase-3 in renal tissue increased at 3 h after reperfusion,and those continued to increase at 12 h after reperfusion and reached the peak at 24 h after reperfusion (P＜0.01),and the activity of caspase-8 increased at 3 b,reached the peak at 12 h after reperfusion and decreased at 24 h after reperfusion (P＜0.01).As compared with S group,the renal tubular injury score,apoptosis rate,the expression of Fas mRNA and the activation of caspase-3 at 3 h,12 h and 24 h of reperfusion and the activation of caspase-8 at 12 h,24 h of reperfusion were all increased in IR group and R group (P＜0.05 or 0.01).As compared with IR group,the renal tubular injury score,apoptosis rate,the expression of Fas mRNA and the activation of caspase-8 and caspase-3 at 3 h,12 h and 24 h of reperfusion were decreased in R group (P＜0.05 or 0.01).Conclusion Remifentanil inhibits cell apoptosis and alleviates renal IR damage by reducing the expression of Fas receptor and the activation of caspase-8 and caspase-3,and regulating the apoptotic signal pathway of Fas.

Objective To investigate the effects of microRNA-486 (miR-486) expression on the cardiac function in rats with myocardial infarction (MI),through direct injection of an adenovirus carrying the miR-486 gene into the myocardium.Methods Totally 120 male rots were divided into 4 groups.Different target materials were infused into the surrounding areas of MI after building a successful disease model.Expression of miR-486 in the surrounding areas of left ventricular MI was detected using real-time PCR at different time points.Cardiac function was measured by cardiac ultrasound at 4 weeks.Using TUNEL,TTC,Masson,and CD31 staining to measure the organic changes in heart tissues.Results The expression of miR-486 in miR-486 group was higher than the other three groups.The expression of miR-486 in the three groups decreased when the time of MI in rats was prolonged.The cardiac function of the miR-486 group was better than that of the MI and AD groups.The MI area in the miR-486 group was smaller than that in the other two groups.Compared to the Sham group,the CVF at the infarct border zone was increased in the MI,Ad,and miR-486 groups.The AI in the MI and Ad groups was significantly increased compared to that in the miR-486 group.MVD was increased in the miR-486 group compared to that in the Sham,MI,and Ad groups.Conclusion miR-486 improved the cardiac function after MI in rats,through lightening collagen deposition,inhibiting apoptosis,and inducing angiogenesis in ischemic regions.

The traditional efficacy of traditional Chinese medicine (TCM) is to summarize the clinical efficacy of TCM under the guidance of TCM theory,and it possess important guiding significance for the clinical use of TCM.Comparing with the modern medical system,the TCM system was different from western medicine in diagnosis and treatment modes,and the disease targets of TCM maybe more extensive than that of western medicine.Based on the traditional efficacy of TCM,combined with modern means of science and technology,the research on material basis and pharmacological mechanism of TCM was beneficial to discovery the new targets,new mechanism,new material and the secondary development of new drug of TCM.Furthermore,it also has far-reaching significance on interpret the modern scientific connotation of TCM efficacy.Therefore,deriving from the traditional efficacy of TCM,the research of modern pharmacodynamic material basis is the source for original research.