High spatial-resolved heat manipulating membrane heterogeneity alters cellular migration and signaling.

Plasma membrane heterogeneity is a key biophysical regulatory principle of membrane protein dynamics, which further influences downstream signal transduction. Although extensive biophysical and cell biology studies have proven membrane heterogeneity is essential to cell fate, the direct link between membrane heterogeneity regulation to cellular function remains unclear. Heterogeneous structures on plasma membranes, such as lipid rafts, are transiently assembled, thus hard to study via regular techniques. Indeed, it is nearly impossible to perturb membrane heterogeneity without changing plasma membrane compositions. In this study, we developed a high-spatial resolved DNA-origami-based nanoheater system with specific lipid heterogeneity targeting to manipulate the local lipid environmental temperature under near-infrared (NIR) laser illumination. Our results showed that the targeted heating of the local lipid environment influences the membrane thermodynamic properties, which further triggers an integrin-associated cell migration change. Therefore, the nanoheater system was further applied as an optimized therapeutic agent for wound healing. Our strategy provides a powerful tool to dynamically manipulate membrane heterogeneity and has the potential to explore cellular function through changes in plasma membrane biophysical properties.

Molecular characteristics and drug resistance analysis of Staphylococcus aureus in orthopedic trauma patients / 中国热带医学

@#Abstract: Objective　To investigate the molecular characteristics and drug resistance of Staphylococcus aureus (SA) isolated from wounds of paatients with orthopedic trauma, and analyze the molecular subtyping, virulence genes and drug resistance of SA in wounds of patients, so as to provide reference for the prevention and treatment of wound SA infection in patients. Methods　From January 2020 to June 2022, a total of 128 SA isolates were collected from wound specimens of orthopedic trauma patients at Wuxi 9th People's Hospital Affiliated to Soochow University. Methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible Staphylococcus aureus (MSSA) were differentiated using PCR. Multilocus Sequence Typing (MLST), staphylococcal protein A (spa), staphylococcal chromatoidal cassette mec (SCCmec), and accessory gene regulator (agr) typing were performed to determine the molecular typing and presence of virulence genes and drug resistance profiles. Results　Among the 128 SA isolates, 76 (59.38%) were MRSA and 52 (40.62%) were MSSA. MRSA typing showed that, MLST was dominated by ST59 (46 strains, 60.53%), spa was dominated by t437 (52.63%), SCCmec was dominated by Ⅰ (42.11%) and Ⅳ (39.47%). MSSA typing showed that, MLST was dominated by ST188 (30.77%), spa was dominated by t189 (61.54%), agr was dominated by Ⅰ (53.85%). In MLST typing, ST59 of MRSA was higher than that of MSSA, and ST188 and ST6 of MRSA were lower than those of MSSA (χ2=36.207, 20.227, 9.984, P<0.05). In spa typing, the t437 of MRSA was higher than that of MSSA, and the t189 of MRSA was lower than that of MSSA (χ2=18.276, 32.781, P<0.05). The virulence genes showed that, the detection rates of hlb and seb in MRSA were higher than those in MSSA (χ2=47.838, 10.261, P<0.05), and the detection rates of cna and ebpS in MRSA were lower than those in MSSA (χ2=26.176, 8.305, P<0.05). Drug susceptibility test showed that, and the drug resistance rates of MRSA and MSSA to vancomycin (VAN) and linezolid (LNZ) were 0. The drug resistance rates of MRSA to oxacillin (OXA), ERY and CLI were 86.84%, 68.42% and 76.32%, which were higher than corresponding 7.69%, 42.31% and 46.15% of MSSA (χ2=78.055, 8.623, 12.200, P<0.05). The analysis of multi-drug resistant strains (MDR) showed that 76 MRSA strains were MDR strains, and 12 of 52 MSSA strains (23.08%) were MDR strains. Conclusions　The molecular characteristics of SA isolated from orthopedic trauma patients' wounds were predominantly associated with MRSA strains of ST59-t437-SCCmec Ⅰ/Ⅳ-MRSA and ST188/ST6-t189-agr Ⅰ. These strains showed higher resistance to oxacillin, erythromycin, clindamycin, and higher susceptibility to vancomycin and linezolid. Such characteristics were closely related to the carriage of virulence genes. Clinicians should pay attention to the presence of MDR MSSA and develop appropriate antimicrobial strategies based on SA's molecular characteristics and antimicrobial resistance.

A Novel Combined Method for Measuring the Three-Dimensional Rotational Angle of a Spherical Joint.

To improve the measurement accuracy of the three-dimensional rotation angle of a spherical joint, a novel approach is proposed in this study, which combines magnetic detection by a Hall sensor and surface feature identification by an eddy current sensor. Firstly, a permanent magnet is embedded in the ball head of a spherical joint, and Hall sensors are set and distributed in the ball socket to measure the variation in the magnetic flux density when the spherical joint rotates, which are related to the 3D rotation angle. In order to further improve the measurement accuracy and robustness, we also set grooves on the ball head and use eddy current sensors to synchronously identify the rotation angle of the ball head. After the combination of two signals is performed, a measurement model is established using the RBF neural network by training, and the real-time measurement of the 3D rotation angle of the spherical joint is realized. The feasibility and superiority of this method are validated through experiments. The experimental results indicate that the measurement accuracy is substantially promoted compared to the preliminary measurement scheme based on spherical coding; the average measurement error of the single axis is reduced by 9'9″. The root mean square errors for the measurements of the 3D rotation angles in this proposed method are as follows: pitch angle α has an error of 1'8″, yaw angle ß has an error of 2'15″, and roll angle γ has an error of 29'6″.

[Clinical Significance of Tfh/Tfr Cell Imbalance in Patients with B-Cell Lymphoma].

OBJECTIVE: To explore the role of follicular helper T cell (Tfh)/ follicular regulatory T cell (Tfr) imbalance in B-cell lymphoma (BCL). METHODS: Sixteen BCL patients who were admitted to the Department of Hematology of The First People's Hospital of Yichang and 20 healthy people from December 2019 to November 2020 were enrolled and respectively divided into observation group and control group. The levels of Tfh and Tfr in peripheral blood were detected by flow cytometry. The changes of Tfh, Tfr, and Tfh/Tfr ratio were compared and the relationship between Tfh/Tfr ratio and efficacy, prognosis was analyzed. RESULTS: Compared with the healthy controls, Tfh and Tfh/Tfr ratio in peripheral blood of the BCL patients increased (P<0.05, P<0.01), while levels of Tfr was decreased (P<0.01). After chemotherapy, Tfh and Tfh/Tfr ratio in peripheral blood of the BCL patients decreased significantly than before chemotherapy (P<0.01), but Tfr was no significant difference. Multivariate analysis showed that Tfh and Tfh/Tfr ratio were positively correlated with international prognostic index (IPI) score and Ann Arbor stage (r=0.626, 0.564, 0.573, 0.608, respectively), while Tfr negatively (r=－0.504, －0.542, respectively). According to the average value of Tfh/Tfr ratio at initial diagnosis, BCL patients were divided into Tfh/Tfr high ratio group and low ratio group. It was found that the complete remission (CR) rate, overall response rate (ORR), and survival time in the high ratio group were significantly lower than the low ratio group (P<0.01). CONCLUSION: There is an imbalance of Tfh/Tfr ratio in peripheral blood of the BCL patients, and those with a high Tfh/Tfr ratio have lower CR, ORR and shorter survival time.

[Effect of acupuncture combined with hypothermia on MAPK/ERK pathway and apoptosis related factors in rats with cerebral ischemia reperfusion injury].

OBJECTIVE: To observe effect of acupuncture combined with hypothermia therapy on MAPK/ERK pathway and apoptosis related factorsin rats suffered cerebral ischemia reperfusion and to explore underlying mechanisms.
 Methods: Middle cerebral artery ischemia model were established.Ninety SD rats were randomly assigned into a blank group, a control group, a model group, an acupuncture group, a mild hypothermia group, and an acupuncture with hypothermia group. After 72 h treatment, nerve function defect scores were observed, and infarction area percent was detected by 2, 3, 5-triphenyl-2H-tetrazolium chloride (TTC) staining; expressions of Bcl-2 and Bax were examined by immunohistochemistry; apoptotic cells were detected by TUNEL assay; and expression levels of phospho-mitogen-activated protein kinase(p-MEK2) and phospho-extracellular signal regulated kinase 1/2 (p-ERK1/2) in the rats' hippocampus ischemic side were determined by Western blot.
 Results: In the rats of the model group, the neural function defect scores, the infarction area percent, the expression level of Bax, and apoptotic cells increased, while the level of Bcl-2 decreased significantly. The level of p-MEK2 and p-ERK1/2 increased obviously compared with the blank and control groups (P<0.05 or P<0.01). After treatment with acupuncture and hypothermia, the neural function defect scores, infarction area percent, and the level of Bax, apoptotic cells and the levels of p-MEK2 and p-ERK1/2 were significantly decreased, while the level of Bcl-2 in the treatment group was significantly elevated (P<0.05 or P<0.01) compared with the model group. Compared with the acupuncture group or the hypothermia group, the neural function defect scores and the levels of p-MEK2 and p-ERK1/2 in the acupuncture combined with hypothermia group were significantly reduced (P<0.05 or P<0.01).
 Conclusion: Acupuncture and hypothermia therapy can improve cerebral function, and reduce the cerebral injury through down-regulation of Bax level, and up-regulation of Bcl-2 level, which is related to reducing the levels of p-MEK2 and p-ERK1/2. The therapeutic effects on cerebral ischemia reperfusion injury for combination of acupuncture with hypothermia are better than those with single application of acupuncture or hypothermia.

[Effect difference between acupuncture and moxibustion for functional dyspepsia: a randomized controlled trial].

OBJECTIVE: To investigate the effect difference between acupuncture and moxibustion for functional dyspepsia (FD). METHODS: Sixty patients with FD were randomized into an acupuncture group (29 cases with 1 rejecting) and a moxibustion group (27 cases with 3 dropping). The corresponding manipulations for 4 courses were applied at Zhongwan (CV 12) and Zusanli (ST 36) in the two groups, continuous 5 times as 1 course with 2 days between two courses, once a day and total 20 times. Leed's dyspepsia questionnaire (LDQ) and Nepean dyspepsia index (NDI) were tested before and after treatment, and safety was evaluated. RESULTS: After treatment, the total LDQ scores decreased in the two groups (both P<0.01), with statistical different value between the two groups (P<0.05). Upper abdominal pain, early satiety, epigastric burning in the acupuncture group were improved more obviously compared with those in the moxibustion group (all P<0.01). The NDI scores in the two groups increased after treatment (both P<0.01), without statistical different value before and after treatment (P>0.05). CONCLUSION: Acupuncture and moxibustion are effective for FD and acupuncture shows superiority.

["Flipped classroom" teaching model into the curriculum of Theories of Different Schools of Acupuncture and Moxibustion:exploration and practice].

The "flipped classroom" teaching model practiced in the teaching of Theories of Different Schools of Acupuncture and Moxibustion curriculum was introduced. Firstly, the roles and responsibilities of teachers were clarified, indicating teachers provided examples and lectures, and a comprehensive assessment system was established. Secondly, the "flipped classroom" teaching model was split into online learning, classroom learning and offline learning. Online learning aimed at forming a study report by a wide search of relevant information, which was submitted to teachers for review and assessment. Classroom learning was designed to communicate study ideas among students and teachers. Offline learning was intended to revise and improve the study report and refined learning methods. Lastly, the teaching practice effects of "flip classroom" were evaluated by comprehensive rating and questionnaire assessment, which assessed the overall performance of students and overall levels of paper; the learning ability was enhanced, and the interest and motivation of learning were also improved. Therefore, "flipped classroom" teaching mode was suitable for the curriculum of Theories of Different Schools of Acupuncture and Moxibustion, and could be recommended into the teaching practice of related curriculum of acupuncture and tuina.

[Acupuncture-moxibustion for chronic allograft nephropathy: a randomized controlled trial].

OBJECTIVE: To observe the effects of acupuncture-moxibustion on chronic allograft nephropathy (CAN) and explore the methods of acupoint selection along meridian for transplanted-kidney-related diseases. METHODS: A total of 180 patients of CAN were randomized into a syndrome differentiation group, a spleen-meridian group, a kidney-meridian group and a control group, 45 cases in each one. A total of 33 cases dropped out before the end of the study, including 8 cases in the syndrome differentiation group, 12 cases in the spleen-meridian group, 13 cases in the kidney-meridian group and no case in the control group. Patients in the control group were treated with conventional western medicine; based on this, patients in other three groups were treated with acupuncture-moxibustion. In the syndrome differentiation group, Qihai (CV 6), Hegu (LI 4), Guanyuan (CV 4), Feishu (BL 13), Shenshu (BL 23), etc. were selected for qi deficiency of lung and kidney; Qihai (CV 6), Zusanli (ST 36), Sanyinjiao (SP 6), Taixi (KI 3), Yinlingquan (SP 9), etc. were selected for deficiency of qi and yin; Ganshu (BL 18), Shenshu (BL 23), Sanyinjiao (SP 6), Taixi (KI 3), Yinlingquan (SP 9), Ququan (LR 8), etc. were selected for yin deficiency of liver and kidney; Zhongji (CV 3), Guanyuan (CV 4), Mingmen (GV 4), Guanyuanshu (BL 26), etc. were selected for yang deficiency of spleen and kidney. In addition, Sanyinjiao (SP 6), Diji (SP 8), Yinlingquan (SP 9), Xuehai (SP 10), etc. were added in the spleen-meridian group; Taixi (KI 3), Zhaohai (KI 6), Fuliu (KI 7), Ciliao (BL 32), etc: were added in the kidney-meridian group. Serum creatinine (Scr), creatinine clearance (Ccr) and 24-hour urinary protein before and after the treatment were com- pared among the four groups. RESULTS: After treatment, 24-hour urinary protein in the acupuncture-moxibustion groups and control group were all reduced (all P < 0.05); compared before treatment, the Scr in the spleen-meridian group was significantly reduced (P < 0.05); the difference of Ccr before and after treatment was insignificant in all the groups (all P > 0.05). Compared with the control group, 24-hour urinary protein in spleen-meridian group could relieve or recover the damage of transplant kidney induced by CAN. A new interlink may be established between the transplanted kidneys and the spleen meridians, indicating that transplanted kidney-related diseases can be treated by selecting acupoints of spleen meridian.

Effects of electroacupuncture at Shangjuxu (ST 37) on interleukin-1beta and interleukin-4 in the ulcerative colitis model rats.

OBJECTIVE: To probe into the mechanisms of electroacupuncture (EA) at Shangjuxu (ST 37) for treatment of the ulcerative colitis (UC). METHODS: Forty male Wistar rats were randomly divided into 4 groups: a normal group, a model group, a Shangjuxu group and a non-acupoint group, 10 rats in each group. The UC rat model was made with enema of trinitro-benzenesulfonic acid (TNBSA), and the changes of interleukin-1beta (IL-1beta) and interleukin-4 (IL-4) contents after EA at Shangjuxu (ST 37) were observed. RESULTS: EA at Shangjuxu (ST 37) could significantly decrease the IL-1beta content and increase the IL-4 content in the colic tissues of the UC rats with significant differences as compared with the model group and the non-acupoint group (P<0.05 or P<0.01). CONCLUSION: The mechanisms of EA at Shangjuxu (ST 37) for treatment of the UC rats is possibly related with the decrease of IL-1beta, a inflammation-promoting cytokine, and the increase of IL-4, a anti-inflammatory cytokine.