Asthma is a chronic inflammatory airway disease,and airway inflammation,airway hyper-respon-siveness and airway remodeling are the major pathological alterations in asthma.Numerous studies have demon-strated sphingosine metabolism disorders exist in asthma patients,and sphingosine-1-phosphate(S1P)is the end product of sphingolipid metabolism,which has become the focus of research as an important mediator of immune and inflammatory diseases,and is closely related to the development of asthma.In this paper,we summarize the role of S1P in the pathological changes of asthma from the relationship between S1P and asthma as well as its application in the clinical diagnosis,treatment and efficacy assessment of asthma,with a view to exploring more directions in the diagnosis and treatment of asthma.

Objective:To evaluate the role of ubiquitin-specific peptidase 22 (USP22) in myocardial ischemia-reperfusion (I/R) injury in diabetic mice.Methods:Seventy-eight SPF male C57BL/6 mice, aged 6-8 weeks, were divided into 6 groups using a random number table method: sham operation group (Sham group, n=12), type 1 diabetes mellitus + sham operation group (T1D+ Sham group, n=12), myocardial I/R injury group (I/R group, n=12), type 1 diabetes mellitus + myocardial I/R injury group (DI/R group, n=12), type 1 diabetes mellitus + myocardial I/R injury + empty vector group (DI/R+ V group, n=15), and type 1 diabetes mellitus + myocardial I/R injury + USP22 overexpression group (DI/R+ U group, n=15). Type 1 diabetes mellitus was induced by intraperitoneal injection of streptozotocin-citrate buffer. Myocardial I/R was induced by ligation of the left coronary artery. At 1 day before developing the myocardial I/R injury model, DI/R+ U group and DI/R+ V group received an intramyocardial injection of USP22 overexpression plasmid or empty vector plasmid, respectively. At 24 h of reperfusion, cardiac function was assessed using the echocardiography to measure the left ventricular ejection fraction and left ventricular fractional shortening. The mice were then sacrificed, and their hearts were harvested for measurement of the myocardial infarct size, for microscopic examination of pathological changes (using HE staining) and for determination of the apoptosis rate (TUNEL staining), reactive oxygen species(ROS) activity (DHE staining), and USP22 expression (by Western blot, immunofluorescence, and immunohistochemistry). Proteomic analysis was performed to identify downstream proteins regulated by USP22, and protein-protein interactions were investigated using co-immunoprecipitation. Results:Compared with Sham group, the cardiac function indices were significantly decreased, the apoptosis rate of myocardial cells and ROS activity were increased, and USP22 expression in myocardial tissues was down-regulated in I/R group ( P<0.05). Compared with I/R group, the percentage of myocardial infarct size was significantly increased, the cardiac function indices were decreased, the apoptosis rate of myocardial cells and ROS activity were increased, and USP22 expression in myocardial tissues was up-regulated ( P<0.05), and the pathological damage to myocardial tissues was aggravated in DI/R group. Compared with DI/R+ V group, the percentage of myocardial infarct size was significantly decreased, the cardiac function indices were increased, the apoptosis rate of myocardial cells and ROS activity were decreased, and USP22 expression in myocardial tissues was up-regulated ( P<0.05), and the pathological damage to myocardial tissues was alleviated in DI/R+ U group. The results of proteomics combined with co-immunoprecipitation experiments showed an interaction between calponin 1 and USP22. Conclusions:During myocardial I/R injury in diabetic mice, USP22 may act as an endogenous protective mechanism, and calponin 1 might be a downstream mechanism through which USP22 exerts its protective effects.

Objective:To explore the curative effects of Nice knot fixation on tuberosity healing in hemiarthroplasty for complex proximal humeral fractures.Methods:A retrospective analysis was conducted of the eligible 32 complex proximal humeral fractures which had been treated at Department of Trauma and Orthopedics, Peking University People's Hospital between May 1, 2016 and May 1, 2019. Nice knot fixation was used to repair greater and lesser tuberosities in hemiarthroplasty for all the patients. There were 6 males and 26 females, aged from 60 to 90 years (mean, 74.9 years). By the Neer classification, there were 4 three-part fractures combined with dislocation, 20 four-part fractures, and 8 four-part fractures combined with dislocation. Shoulder joint X-rays were taken at postoperative 1, 2, 3, 6, and 12 months at the outpatient clinic to evaluate the patients' shoulder joint mobility, visual analog scale (VAS) pain score and Constant-Murley shoulder score. Tuberosity healing was assessed based on the X-rays and related complications were recorded.Results:The 32 patients received complete follow-up for 12 to 25 months (average, 17.82 months). At the 12-month follow-up, their shoulder flexion averaged 131.3° (from 80° to 155°), abduction 126.9° (from 80° to 155°), external rotation 48.4° (from 30° to 60°), internal rotation the L2 level, VAS pain score 0.9 (from 0 to 5), and Constant-Murley score 83.4 (from 58 to 96). The rate of patient satisfaction was 87.5%(28/32). Tuberosity-related complications were observed in 6 cases with an incidence of 18.8%. Complications like infection and prosthetic loosening were found in none of the patients.Conclusion:In hemiarthroplasty for complex proximal humeral fractures, application of Nice knot to fixate greater and lesser tuberosities can lead to rigid fixation, definite curative effects and a low incidence of tuberosity-related complications.

Objective:To explore the potential mechanism and feasibility of sonic hedgehog (SHH) signal pathway inhibitor NVP-LDE225 combined with radiotherapy in the treatment of melanoma.Methods:The Gli1 mRNA expression of the melanoma cells (Melan-A and SK-MEL-2) was detected by qPCR. After treatment with NVP-LDE225, GDC-0449 or combined with radiation for 24 hours, the number and activity of Melan-A and SK-MEL-2 were detected by cell counting and CCK-8 kit. The survival and proliferation ratio of Melan-A and SK-MEL-2 were detected by cell cloning. The changes of cell cycle of melanoma Melan-A cells were determined by flow cytometry. The levels of the Bax and Caspase3 of Melan-A apoptosis protein in melanoma cells were detected by Western blot.Results:NVP-LDE225, an inhibitor of Smo, decreased the mRNA expression of Gli1 in the melanoma cells in a dose-dependent manner, inhibited the proliferation ratio of the melanoma cells, induced apoptosis, and arrested melanoma cells in G 0 / G 1 phase. Gamma ray irradiation after NVP-LDE225 treatment further inhibited the SHH signal pathway, arrested the melanoma cells in G 2 / M phase, and further increased the inhibitory effect on melanoma cell proliferation. Conclusions:NVP-LDE225, an inhibitor of Smo, can inhibit SHH signal pathway in melanocytes, suppress cell proliferation, and further increases the effect of inhibiting cell proliferation after combining with irradiation. It can be used as a potential drug in combination with radiotherapy in the treatment of melanoma, which is worthy of further study.

Objective:To evaluate the role of hippocampal REV-ERBα in postoperative cognitive dysfunction in rats.Methods:Thirty-two SPF healthy male Sprague-Dawley rats, aged 12-14 weeks, weighing 360-380 g, were divided into 4 groups ( n=8 each) using a random number table method: control group (group C), surgery group (group S), surgery + dimethyl sulfoxide (DMSO) group (group SD), and surgery + SR9009 group (group SS). Exploratory laparotomy was performed under sevoflurane anesthesia in S, SD and SS groups.Normal saline containing 0.1% DMSO was injected into hippocampal CA1 area at 1 h before laparotomy, with 2 μl on each side in group SD, and REV-ERBα agonist SR9009 (in normal saline containing 0.1% DMSO) was injected into hippocampal CA1 area at 1 h before laparotomy, with 2 μl on each side in group S+ SR9009.Morris water maze test was performed at 1 and 3 days after operation.Rats were sacrificed at 1 h after the end of Morris water maze test on day 3 after surgery, and the hippocampal tissues were obtained for determination of the expression of REV-ERBα, Brain and Muscle ARNT-Like 1 (BMAL1) protein, synaptophysin (SYN), postsynaptic density (PSD)-95 protein and N-methyl-D-aspartate receptor 2B subunit (GRIN2B) (by Western blot) and microscopic examination of the morphology of hippocampal neurons and Nissl bodies (by Nissl staining), and the viable neurons were counted. Results:Compared with group C, the percentage of time of staying at the target quadrant was significantly decreased, and the number of crossing platform was reduced on days 1 and 3 after exploratory laparotomy, the expression of REV-ERBα, BMAL1, PSD95, SYN and GRIN2B was down-regulated, and the number of viable neurons was decreased in group S and group SD ( P<0.05). Compared with group S and group SD, the percentage of time of staying at the target quadrant and the number of crossing platform were significantly increased on days 1 and 3 after exploratory laparotomy, the expression of REV-ERBα and PSD95 was up-regulated, the number of viable neurons was increased ( P<0.05), and no significant change was found in the expression of BMAL1, SYN and GRIN2B in group SS ( P>0.05). There was no significant difference in the indexes mentioned above between group S and group SD ( P>0.05). Conclusions:Activation of REV-ERBα can improve postoperative cognitive dysfunction, and the mechanism may be related to up-regulation of PSD95 expression in hippocampus and reduction of neuronal damage in rats.

OBJECTIVE：To analyze the chemotypes of volatile components from Perillae Folium of different germplasms ，and to investigate the relationship of germplasm and leaf color with chemotype. METHODS ：The fingerprints of volatile components from 30 batches of Perillae Folium were prepared by GC-MS with P 4 peak as reference. Similarity Evaluation System for TCM Chromatographic Fingerprint （2004A edition ）was applied to evaluate the similarity and confirm common peaks. The volatile components of Perillae Folium were determined by the same GC-MS method. Qualitative Navigator （B.08.00）software was used to analyze and compare with NIST 17.0 standard mass spectrum database. The compounds corresponding to the peak were analyzed ； clustering analysis was carried out with Origin 2018 software. RESULTS ：There were 13 common peaks in the fingerprints of volatile components from 30 batches of Perillae Folium . The similarities were 0.13-1.00. Totally 54 components were identified from 30 batches of Perillae Folium of different germplasm. Cluster analysis showed that 30 batches of Perillae Folium samples could be clustered into three categories ；among them ，SCY-1，YNT-9，YNX-17，YN-28 were clustered into one category ，with phenylpropanoid-elemicin（PP-e as ）the main volatile component ，being PP-e type ；GS-4，GS-7，GS-11，GS-19，HBA-14， HBA-20，GZZ-8，LN-39，GSL-27，GSQ-32，GSQ-33，GST-31，YNW-12，LN-38 were clustered into one category ，and the content of perilla ketone （PK）in them was the highest except for LN- 38， being PK type [the content of phenylpropanoid-apiol（PP-a）in LN- 38 was higher than that of perilla ketone ，being PP-a type] ；HBS-2，HBS-3，HBS-6， C201859）HBS-15，HBS-16，HBS-24，HBS-25，GX-26，SXS-30，SCC- 36，RB-37，SC-29 were clustered into one category ，and thecontent of perillaldehyde （PA）was the highest ，being PA type.The color characteristics of Perillae Folium of different germplasm showed that Perilla frutescens （L.） Britt. var.frutescens with green leaves on both sides was PK type ，while P. frutescens （L.）Britt. var. arguta with purple leaves on one or both sides was PA type ，and P. frutescens （L.） Britt var. auriculato-dentata C. Y. Wu et Hsuan ex H. W. Li was PP-e type. CONCLUSIONS：The chemotype of volatile components in Perillae Folium have a certain corresponding relationship with their leaf colors. Most of P. frutescens （L.）Britt. var. arguta with purple leaves on one side or both sides are PA type. P. frutescens （L.） Britt. var. acuta （Thunb.）Kudo，P. frutescens （L.）Britt var. auriculato-dentata C. Y. Wu et Hsuan ex H. W. Li and P. frutescens （L.）Britt. var. frutescens with green leaves on both sides do not belong to PA type ，among which P. frutescens （L.）Britt var. frutescens is PK type ，while P. frutescens （L.）Britt var. auriculato-dentata C. Y. Wu et Hsuan ex H. W. Li is mostly PP-e type.

Objective:To evaluate the role of hippocampal histone deacetylases (HDACs) in perioperative neurocognitive disorders (PND) and the relationship with postsynaptic dense protein 95 (PSD95) in rats.Methods:Sixty clean-grade healthy male Sprague-Dawley rats, aged 10-14 weeks, weighing 250-280 g, were divided into 3 groups ( n=20 each) using a random number table method: control group (group C), surgery group (group S) and HDAC inhibitor MS-275 group (group MS-275). Exploratory laparotomy was performed under 3% sevoflurane anesthesia in group S. MS-275 10 mg/kg was intraperitoneally injected at 0.5 h before exploratory laparotomy in group MS-275.Morris water maze tests were performed on 1 day before surgery and 1, 3 and 7 days after surgery.Ten rats were sacrificed on 1 day after surgery, and hippocampal tissues were obtained for determination of the expression of HDAC1-3 and PSD95 protein and mRNA by Western blot and real-time polymerase chain reaction, respectively.The density of hippocampal neurons was determined by the Nissl staining. Results:Compared with group C, the postoperative escape latency was significantly prolonged, the number of crossing the original platform was decreased, the density of hippocampal neurons was decreased, the expression of HDAC2 protein and mRNA was up-regulated, and the expression of PSD95 protein and mRNA was down-regulated in group S ( P<0.05 or 0.01). Compared with group S, the postoperative escape latency was significantly shortened, the number of crossing the original platform was increased, the density of hippocampal neurons was increased, the expression of HDAC2 protein and mRNA was down-regulated, and the expression of PSD95 protein and mRNA was up-regulated in group MS-275 ( P<0.05 or 0.01). There was no significant difference in the expression of HDAC1 and HDAC3 protein and mRNA among the three groups ( P>0.05). Conclusion:HDAC2 is involved in the pathophysiological mechanism of PND by down-regulating the expression of PSD95 in rats.

Objective:To explore the clinical effect of X-N advancement flap in repairing pressure ulcer on the buttock or back.Methods:From June 2018 to June 2019, 20 patients with grade Ⅳ pressure ulcers on the buttock or back were hospitalized and treated in the Department of Traumatology, Burns and Plastic Surgery of Fourth Affiliated Hospital of Guangxi Medical University, including 15 males and 5 females, aged 48-89 years. The area of the patient′s wound was 8 cm×5 cm-15 cm×12 cm after debridement, and all were repaired with the X-N advancement flap designed by the author. The flap was designed according to the direction of skin relaxation on both sides of the wound, and the skin was incised in X-shape and sutured in N-shape. The width and advancement distance of the flap were recorded, and the ratio of the advancement distance to the width of the flap was calculated. The flap survival, complication, and follow-up were observed and recorded.Results:The width of the flap was (5.9±1.2) cm, the advancement distance of the flap was (10.3±2.5) cm, and the ratio of the advancement distance to the width of the flap was 1.8±0.4. All the flaps survived, and none of the flaps had blood flow disorder. Local dehiscence occurred in the flap of one patient 1 week after surgery, which was healed after laying on the floating bed, strengthened care, and wound dressing change. The flap of one patient developed infection 5 days after surgery, which was healed after partial suture removal, smooth drainage, and replacement with sensitive antibiotics. The wounds of the remaining 18 patients were all cured. After 3 months of follow-up, the flaps survived well with good elasticity and texture.Conclusions:The X-N advancement flap can make the skin and soft tissue move forward effectively. It is simple and effective to repair pressure ulcers on the back or buttock of patients with this flap, which is worthy of clinical promotion and application.

OBJECTIVE： To establish a method for simultaneous determination of gallic acid， cinnamic acid and catechin in 3 processed products of Rheum officinale. METHODS： RP-HPLC method was established. The determination was performed on Thermo ScientificTM Hypersil GOLD Dim column with mobile phase consisted of methanol-0.1％ phosphoric acid solution （gradient elution） at the flow rate of 1.0 mL/min. The detection wavelength was set at 278 nm， and the column temperature was 30 ℃. The sample size was 10 μL. RESULTS： The linear range of gallic acid， cinnamic acid and catechin were 0.126 2-1.262 0 μg（r＝0.999 9）， 0.036 2-0.362 0  μg（r＝0.999 9） and 0.177 9-1.779 4 μg（r＝0.999 8）， respectively. Quantitative limits were 25.4， 28.2， 62.5 ng， and detection limits were 6.2， 3.6， 11.8 ng， respectively. RSDs of precision， stability， repeatability and durability tests were all less than 3％. The recoveries ranged from 94.64％-102.71％（RSD＝2.74％， n＝9）， 95.35％-102.49％（RSD＝2.44％， n＝9）， 93.56％-103.66％（RSD＝3.27％， n＝9）. The determination results showed that the contents of gallic acid and cinnamic acid in prepared R. officinale were higher， and the order of both were prepared R. officinale＞steamed R. officinale＞raw R. officinale. The content of catechin in raw R. officinale was higher， and the order of it was raw R. officinale＞ steamed R. officinale＞prepared R. officinale. CONCLUSIONS： The method is sensitive， reliable and reproducible. It can be used to determine the contents of gallic acid， cinnamic acid and catechins in 3 processed products of R. officinale simultaneously.

OBJECTIVE： To study the anti-inflammatory effect and its mechanism of the extract of Dcsmodium microphyllum， so as to provide experiment reference for further study of D. microphyllum. METHODS： Acute inflammatory model was established by xylene，glacial acetic acid and carrageenan. Using dexamethasone as positive control （0.005 g/kg）， inhibitory effects of intragastric different doses of the extract of D. microphyllum （50， 30， 15 g/kg） on xylene-induced ear swelling in normal mice and adrenalectomized mice， glacial acetic acid-induced permeability increasing of abdominal capillaries in normal mice， carrageenan-   induced paw swelling in normal mice and adrenalectomized mice were investigated. The levels of MDA， SOD and NO in the inflammatory tissue of toes of adrenalectomized mice were detected in carrageenan-induced inflammation model. Blank group was set for control （ig. equal volumn of water）. RESULTS： Compared with blank group， ear swelling degree of normal mice and adrenalectomized mice were decreased significantly in D. microphyllum extract high-dose and medium-dose groups while inhibitory rate of ear swelling was increased significantly； the permeability of abdominal capillaries of normal mice was significantly decreased in D. microphyllum extract groups； the swelling degree of toes in normal mice of D. microphyllum extract high-dose and middle-dose groups and adrenalectomized mice were significantly decreased while inhibitory rate of toe swelling was increased significantly （P＜0.05 or P＜0.01）. The levels of MDA and NO in the toe inflammatory site of adrenalectomized mice were decreased significantly in D. microphyllum extract high-dose and medium-dose groups， while the level of SOD was increased significantly （P＜0.05）. CONCLUSIONS： D. microphyllum extract can inhibit acute inflammation in mice significantly. Its anti-inflammatory mechanism is associated with decreasing MDA and NO while increasing SOD levels， and the anti-inflammatory effect does not depend on the hypothalamus-pituitary-adrenal axis system.