Roles and application of exosomes in the development, diagnosis and treatment of gastric cancer.

As important messengers of intercellular communication, exosomes can regulate local and distant cellular communication by transporting specific exosomal contents and can also promote or suppress the development and progression of gastric cancer (GC) by regulating the growth and proliferation of tumor cells, the tumor-related immune response and tumor angiogenesis. Exosomes transport bioactive molecules including DNA, proteins, and RNA (coding and noncoding) from donor cells to recipient cells, causing reprogramming of the target cells. In this review, we will describe how exosomes regulate the cellular immune response, tumor angiogenesis, proliferation and metastasis of GC cells, and the role and mechanism of exosome-based therapy in human cancer. We will also discuss the potential application value of exosomes as biomarkers in the diagnosis and treatment of GC and their relationship with drug resistance.

Inhibition of FABP5 attenuates inflammatory bowel disease by modulating macrophage alternative activation.

Fatty acid binding protein 5 (FABP5) is an intracellular chaperone of fatty acid molecules that regulates lipid metabolism and cell growth. However, its role in intestinal inflammation remains enigmatic. Through examination of human tissue samples and single-cell data, we observed a significant upregulation of FABP5 within the mucosa of patients afflicted with ulcerative colitis (UC) and Crohn's disease (CD), predominantly localized in intestinal macrophages. Herein, we investigate the regulation of FABP5-IN-1, a FABP5 inhibitor, on various cells of the gut in an inflammatory environment. Our investigations confirmed that FABP5 ameliorates DSS-induced colitis in mice by impeding the differentiation of macrophages into M1 macrophages in vitro and in vivo. Furthermore, following FABP5-IN-1 intervention, we observed a notable restoration of intestinal goblet cells and tuft cells, even under inflammatory conditions. Additionally, FABP5-IN-1 exhibits a protective effect against DSS-induced colitis by promoting the polarization of macrophages towards the M2 phenotype in vivo. In summary, FABP5-IN-1 confers protection against DSS-induced acute colitis through a multifaceted approach, encompassing the reduction of inflammatory macrophage infiltration, macrophage polarization, regulating Th17/Treg cells to play an anti-inflammatory role in IBD. The implications for IBD are underscored by the comprehensive in vivo and in vitro experiments presented in this article, thereby positioning FABP5 as a promising and novel therapeutic target for the treatment of IBD.

Mechanisms and applications of ferroptosis-associated regulators in cancer therapy and drug resistance.

Iron is an essential element for almost all living things. Both iron excess and iron deficiency can damage the body's health, but the body has developed complex mechanisms to regulate iron balance. The imbalance of iron homeostasis and lipid peroxidation are important features of ferroptosis. In this review, we summarize the latest regulatory mechanisms of ferroptosis, the roles of relevant regulators that target ferroptosis for cancer therapy, and their relationship to drug resistance. In conclusion, targeting ferroptosis is an important strategy for cancer therapy.

Improving therapeutic resistance: beginning with targeting the tumor microenvironment.

Cancer is a serious threat to human health and life. The tumor microenvironment (TME) not only plays a key role in the occurrence, development and metastasis of cancer, but also has a profound impact on treatment resistance. To improve and solve this problem, an increasing number of strategies targeting the TME have been proposed, and great progress has been made in recent years. This article reviews the characteristics and functions of the main matrix components of the TME and the mechanisms by which each component affects drug resistance. Furthermore, this article elaborates on targeting the TME as a strategy to treat acquired drug resistance, reduce tumor metastasis, recurrence, and improve efficacy.

ARHGAP11A Promotes the Malignant Progression of Gastric Cancer by Regulating the Stability of Actin Filaments through TPM1.

The mechanism underlying the poor prognosis of gastric cancer, including its high degree of malignancy, invasion, and metastasis, is extremely complicated. Rho GTPases are involved in the occurrence and development of a variety of malignant tumors. ARHGAP11A, in the Rho GTPase activating protein family, is highly expressed in gastric cancer, but its function and mechanism have not yet been explored. In this study, the effect of ARHGAP11A on the occurrence and development of gastric cancer and the mechanism related to this effect were studied. The expression of ARHGAP11A was increased in gastric cancer cells and tissues, and high ARHGAP11A expression in tissues was related to the degree of tumor differentiation and poor prognosis. Moreover, ARHGAP11A knockout significantly inhibited cell proliferation, cell migration, and invasion in vitro and significantly inhibited the tumorigenic ability of gastric cancer cells in nude mice in vivo. Further studies revealed that ARHGAP11A promotes the malignant progression of gastric cancer cells by interacting with TPM1 to affect cell migration and invasion and the stability of actin filaments. These results suggest that ARHGAP11A plays an important role in gastric cancer and may become a useful prognostic biomarker and therapeutic target for gastric cancer patients.

Predictive value of lncRNA ZFAS1 in patients with lumbar disc degeneration.

BACKGROUND: Increasing evidences have indicated the association of non-coding RNAs with the progression of lumbar disc degeneration (LDD), but the role of lncRNA ZFAS1 in LDD remains undefined. Therefore, this study was designed to determine the predictive value of lncRNA ZFAS1 in patients with LDD. METHODS: A total of 80 patients with LDD confirmed and treated in the Gansu Provincial Hospital from May 2018 to May 2020 were enrolled into the patient group, and 50 healthy controls who concurrently underwent physical examination in our hospital were enrolled into the control group. The expression and diagnostic value of serum lncRNA ZFAS1 in the two groups were determined. The expression of lncRNA ZFAS1 was compared between the two groups before and one month after therapy, and the associations of lncRNA ZFAS1 with inflammatory factors were analyzed. In addition, logistic regression was carried out to analyze risk factors for the prognosis of patients, and corresponding curves about prediction were drawn. RESULTS: The patient group showed a notably higher lncRNA ZFAS1 level than the control group (P<0.001), and the area under the receiver operating characteristic (ROC) of lncRNA ZFAS1 in diagnosing LDD was 0.807. In addition, after therapy, the patient group showed a remarkable decrease in serum lncRNA ZFAS1 (P<0.01). Serum lncRNA ZFAS1 was positively correlated with serum TNF-α, IL-6 and IL-1ß in patients (all P<0.05). Moreover, serum lncRNA ZFAS1 in the good efficacy group was notably lower than that in the general efficacy group (P<0.01). Age and lncRNA ZFAS1 expression before therapy were independent risk factors for patients' prognosis (both P<0.05). CONCLUSION: LncRNA ZFAS1 is highly expressed in patients with LDD and is a potential prognostic indicator for LDD.

[Clinical application of percutaneous spinal endoscopy debridement and lavage in sacroiliac joint tuberculosis].

OBJECTIVE: To investigate the feasibility and clinical efficacy of percutaneous spinal endoscopic debridement and lavage for the treatment of sacroiliac joint tuberculosis. METHODS: The clinical data of 7 patients with sacroiliac joint tuberculosis treated with percutaneous spinal endoscopic debridement and lavage from January 2007 to April 2009 were retrospectively analyzed. There were 2 males and 5 females, aged from 29 to 69 years old, 4 cases on the right side of the lesion and 3 cases on the left side. The course ranged from 8 to 144 months. According to Kim classification, 5 cases were type Ⅲ and 2 cases were type Ⅳ. All patients were treated with HRZE quadruple anti tuberculosis drugs for 2 to 6 weeks beforeoperation. VAS, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and Oswestry Disability Index (ODI) were compared before and after surgery. RESULTS: All the operations were successful, the intraoperative blood loss was less than 50 ml on average, and no complications such as hematoma and infection were occurred. The follow-up time of 7 cases ranged from 18 to 40 months. Pain relief was obvious, and there was a statistical result in the VAS, ESR, and ODI of the patients at 1, 3, 6, 12, 18 months after operation compared with before treatment. At the final follow-up, the patient's clinical, imaging and laboratory examinations showed that the infection had disappeared, and the patient returned to normal life and work. CONCLUSION: Percutaneous spine endoscopic debridement and lavage has less tissue trauma, targeted operation, definite curative effects, and quick postoperative recovery, which has explored new options for minimally invasive treatment of sacroiliac joint tuberculosis.

Nebivolol combined with tetrahydrobiopterin affects diastolic function in spontaneously hypertensive rats via the nitric oxide/cyclic guanosine monophosphate signalling pathway.

BACKGROUND: Hypertension is the the primary cause of diastolic heart failure. Oxidative stress plays an important role in cardiac diastolic dysfunction caused by hypertension. The occurrence of oxidative stress is related to the level of nitric oxide (NO) in the body. Tetrahydrobiopterin (BH4) is an essential cofactor for NO synthesis. Nebivolol can reduce myocardial oxidative stress and increase NO activity. Therefore, we investigated the effects of monotherapy or combination therapy of different doses of BH4 and nebivolol on cardiac diastolic function in spontaneously hypertensive rats, and preliminarily expounded the related mechanisms. METHODS: Left ventricular function was evaluated by non-invasive echocardiographic assessment and invasive right carotid artery catheterization methods. ELISA was used to measure myocardial 3-nitrotyrosine content, NO production, and cyclic guanosine monophosphate (cGMP) concentration in the myocardium; quantitative real-time PCR (qRT-PCR) was used to determine endothelial nitric oxide synthase (eNOS), phospholamban and sarcoplasmic reticulum Ca2+-ATPase 2a (SERCA2a) mRNA expression levels; Western blot was used to detect the protein expression levels of eNOS and eNOS dimers in myocardial tissue, and immunohistochemical detection of cGMP expression in the myocardium was performed. RESULTS: Studies have shown that compared with those in the control group, NO generation and the expression level of myocardial eNOS mRNA, eNOS expression of dimers, phospholamban, SERCA2a and cGMP increased significantly after the combined intervention of BH4 and nebivolol, while the expression of 3-nitrotyrosine was significantly decreased. CONCLUSIONS: The combined treatment group had a synergistic effect on reducing myocardial oxidative stress, increasing eNOS content, and increasing NO production, and had a more obvious protective effect on diastolic dysfunction through the nitric oxide/cyclic guanosine monophosphate (NO/cGMP) pathway.

Rho GTPases and related signaling complexes in cell migration and invasion.

Cell migration and invasion play an important role in the development of cancer. Cell migration is associated with several specific actin filament-based structures, including lamellipodia, filopodia, invadopodia and blebs, and with cell-cell adhesion, cell-extracellular matrix adhesion. Migration occurs via different modes, human epithelial cancer cells mainly migrate collectively, while in vivo imaging studies in laboratory animals have found that most cells migrate as single cells. Rho GTPases play an important role in the process of cell migration, and several Rho GTPase-related signaling complexes are also involved. However, the exact mechanism by which these signaling complexes act remains unclear. This paper reviews how Rho GTPases and related signaling complexes interact with other proteins, how their expression is regulated, how tumor microenvironment-related factors play a role in invasion and metastasis, and the mechanism of these complex signaling networks in cell migration and invasion.

Effects of Tetrahydrobiopterin Combined with Nebivolol on Cardiac Diastolic Function in SHRs.

This study aimed to evaluate the effects of combined use of tetrahydrobiopterin (BH4) and nebivolol on cardiac diastolic dysfunction in spontaneously hypertensive rats (SHRs). Twelve-week-old male SHRs were treated with BH4, nebivolol, or a combination of both. Left ventricle function was evaluated, and reactive oxygen species (ROS) production (including dihydroethidium (DHE) and 3-nitrotyrosine (3-NT)), nitric oxide synthase (NOS) activity and the level of NO in myocardial tissue were determined. The expression levels of endothelial NOS (eNOS), phospholamban (PLN), sarcoplasmic reticulum Ca2+ ATPase (SERCA2a), ß3-adrenoceptor, cyclic guanosine monophosphate (cGMP), and protein kinase G (PKG) were assayed. Treatment with BH4, nebivolol, or both reversed the noninvasive indexes of diastolic function, including E/E' and E'/A', and the invasive indexes, including time constant of isovolumic left ventricle (LV) relaxation (tau), -dP/dtmin, -dP/dtmin/LV systolic pressure (LVSP), and LV end-diastolic pressure (LVEDP) in SHRs. mRNA and protein expression levels of eNOS dimer, phosphorylated PLN, SERCA2a, cGMP, and PKG in the myocardium of treated SHRs were significantly up-regulated compared with those in control rats (p < 0.05 or p < 0.01). The expression levels of 3-NT and DHE were reduced in all treated groups (p < 0.05 or p < 0.01). Notably, combined use of BH4 and nebivolol had better cardioprotective effects than monotherapies. BH4 or nebivolol has a protective effect on diastolic dysfunction in SHRs, and BH4 combined with nebivolol may exert a synergistically cardioprotective effect through activation of ß3-adrenoceptor and the NO/cGMP/PKG signaling pathway.

[Minimal invasive surgery-transforaminal lumbar interbody fusion combined with expanded pedicle screw through Mast Quadrant channel for the treatment of senile pyogenic discitis and vertebral osteomyelitis].

OBJECTIVE: To investigate the feasibility and clinical efficacy of minimal invasive surgery-transforaminal lumbar interbody fusion (MIS-TLIF) combined with expanded pedicle screw (EPS) in the treatment of elderly patients with pyogenic discitis and vertebral osteomyelitis (PDVO). METHODS: The clinical data of 11 elderly patients with pyogenic discitis and vertebral osteomyelitis treated from January 2016 to June 2017 were retrospectively analyzed, including 7 males and 4 females, aged from 59 to 79 years old with an average of (68.09±5.34) years. The MIS-TLIF technique was used assisted by the Quadrant channel under general anesthesia for the debridement and bone fusion of these 11 elderly patients. The posterior fixation was performed with EPS. The operation time, intraoperative blood loss, intraoperative blood transfusion, and postoperative time of out of bed, postoperative complications and erythrocyte sedimentation rate(ESR)were recorded. Visual analogue scale (VAS) was used to evaluate the clinical effects and the imaging data were used to observe lumbar fusion. RESULTS: All the operations were successfully performed, the debridement was thorough, bone fusion was adequate, and no complications such as dural sac and nerve root injury were found. The operation time and intraoperative blood loss was(179.55±59.05) min and (174.55±49.22)ml, respectively. Concentrated red blood cells of (109.09±97.00) ml and plasma of (72.73±100.91) ml were given during operation. The time of out of bed was(1.19±0.83) d. All the incisions obtained healing at the first stage. The average follow-up time was(19.27±11.63) months. VAS scoring at 1 week and 6 months after surgery was 3.73±1.01 and 2.18±0.40;ESR at 6 weeks after surgery was(19.27±2.61) mm/h(decreased by more than 50%), at 6 months after surgery was (9.55±1.01) mm/h, both within normal range. During the follow-up period, all patients reached the clinical cure standard, and the bone fusion time was(5.54±1.51) months. CONCLUSIONS: MIS-TLIF combined with EPS through Quadrant channel in the treatment of elderly patients with PDVO has achieved minimally invasive surgery. The feasibility of this method also has been verified and satisfactory clinical results have been achieved. It is a safe and reliable treatment for elderly patients with spinal suppurative osteomyelitis.

[Clinical application of anterior thoracoscopically assisted surgery with posterior one-stage total en block spondylectomy for thoracic spinal tumor].

OBJECTIVE: To investigate the clincial effects and feasibility of anterior thoracoscopically assisted surgery (TAS) with posterior one-stage total en block spondylectomy(TES) for thoracic spinal tumour. METHODS: From October 2014 to January 2016, 4 patients with thoracic spinal tumour were treated by anterior thoracoscopically assisted surgery with posterior one-stage total en block spondylectomy. There were 2 males and 2 females, aged 16, 35, 46, 60 years. Courses of disease were 1, 4, 6, 9 months. The tumor occurred at T4, T6, T130 segment in 1 case respectively, at double T7/T8 segments in 1 case. Preoperative visual analogue scores(VAS) were 4, 5, 6, 8 points. Frankel grade of neurologic function was grade B in 2, D in 1, and E in 1. SF-36 quality of life scores were 38, 65, 35, 29 points, including 2 cases of primary spinal tumors, 2 cases of metastatic spinal tumors. According to the classification of Tomita, 1 case was type III, 2 cases were type IV, 1 case was type VI. And according to the WBB staging, 4-9/ABCD was in 2 cases, 5-8/ABC compliated with 1-3 was in 1 case, 6-7/ABC was in 1 case. Surgical procedure: With lateral position, the thoracoscope channel was inserted. The involved intervertebral vessels and corresponding intercostal vessels were ligated, while the prevertebral large vessels were completely separated and protected. The front halves of superior and inferior involved vertebral discs were removed. Then the patients were changed to prone position, posterior one-stage total en block spondylectomy, titanium cage bone graft (allograft bone), pedicle screw fixation were performed. RESULTS: All of the operations were successful and the patients were followed up for 34, 10, 11, 12 months. Pleural effusion occurred in 1 case after operation, and pleural closed drainage was done. All incisions got primary healing; and all patients showed significant pain relief (P<0.005), with the VAS score decreasing to 2(2 cases) and 3(2 cases) scores, 2 months after surgery. No nerve functional injury aggravated. SF-36 quality of life score obviously improved with postoperative scores for 88, 92, 71, 80 at 3 months after operation. No recurrent vertebral tumor, internal fixation lossening or breakage was found at follow-up points of 3, 6, 12 months. One patient with lung cancer died of multiple organ failure at 11 months after operation. CONCLUSIONS: With anterior TAS, vertebral anterior vessels, intervertebral blood vessels, intercostal vessels were successfully separated or ligated, intraoperative bleeding was effectively controlled, lung and esophagus were effectively protected, and the tumor received wide excision. Anterior TAS and one-stage posterior TES could significantly reduce the surgical trauma and the risk of surgery.

[Intraosseous lipoma: retrospective analysis of 19 patients].

OBJECTIVE: To investigate the diagnostic and therapeutic procedures of intraosseous lipoma. METHODS: From June 1986 to January 2016, 19 patients with intraosseous lipoma were treated including 12 males and 7 females, aged from 24 to 76 years, a predilection aged was from 40 to 50 years in 13 cases. Symptoms presented with pain or swelling in 15 patients, the lesions were found incidentally in 3 patients, another case was bone defect lipoma replacement after curettage of bone cyst for 4 years. On plain X-ray flims of all bones showed a well-circumscribed radiolucent area. Diagnosis was established with CT or MRI. Among them, 16 cases were treated by surgical operation, 3 cases were treated by concervative treatment. All patients' clinical data, histologic findings and X-ray, CT and MRI were analysed. RESULTS: Total 19 patients were followed up from 9 to 42 months with an average of 15 months. There was no local tumor recurrence in 16 patients after excising the tumors, the remaining 3 patients showed no enlargement of the lesion. CONCLUSIONS: Surgical intervention is considered as an unnecessary in the patients diagnosied intraosseous lipoma by MRI or CT. Patients with symptomatic should adopt surgical treatment with curettage and bone grafting.

Measles Outbreak among Previously Immunized Adult Healthcare Workers, China, 2015.

Measles is caused by measles virus belonging to genus Morbillivirus of the family Paramyxoviridae. Vaccination has played a critical role in controlling measles infection worldwide. However, in the recent years, outbreaks of measles infection still occur in many developing countries. Here, we report an outbreak of measles among healthcare workers and among the 60 measles infected patients 50 were healthcare workers including doctors, nurses, staff, and medics. Fifty-one patients (85%) tested positive for IgM antibodies against the measles virus and 50 patients (83.3%) tested positive for measles virus RNA. Surprisingly, 73.3% of the infected individuals had been previously immunized against measles. Since there is no infection division in our hospital, the fever clinics are located in the Emergency Division. In addition, the fever and rash were not recognized as measles symptoms at the beginning of the outbreak. These factors result in delay in isolation and early confirmation of the suspected patients and eventually a measles outbreak in the hospital. Our report highlights the importance of following a two-dose measles vaccine program in people including the healthcare workers. In addition, vigilant attention should be paid to medical staff with clinical fever and rash symptoms to avoid a possible nosocomial transmission of measles infection.

[Study on the Chemical Constituents of Litchi chinensis Pericarp( â ¡)].

Objective: To study the chemical constituents of Litchi chinensis pericarp. Methods: The compounds were isolated by Sephadex LH-20, MCI gel CHP 20 P, Toyopearl Butly-650 C, Toyopearl WH-40 F column chromatographies and semi-preparative HPLC, the structures were elucidated by NMR and mass spectroscopic MS data analysis. Results: 14 compounds were obtained and their structures were identified as quercetin( 1), chrysoeriol( 2),kaemperol-3-O-ß-D-glucoside( 3), manghaslin( 4), isorhamnetin-3-O-robinobioside( 5), ( +)-gallocatechin( 6), (-) epicatechin-3-O-gallate( 7), cinnamtannin B-1( 8), isolariciresinol-9-O-ß-D-xyloside( 9), ( +)-5-methoxyisolariciresinol-9-O-ß-D-xylopyranoside( 10), vanillic acid( 11), 3, 4, 3', 4'-tetrahydroxy biphenyl( 12), tachioside( 13) and isotachioside( 14). Conclusion: Compounds 1 ~ 7,9 ~ 14 are obtained from this plant pericarp for the first time.

[Treatment of displaced femoral neck fracture in young adults with close reduction and femoral neck locking plate fixation].

OBJECTIVE: To investigate the clinical effects of close reduction and proximal femoral locking plate fixation for the treatment of femoral neck fractures in young adults. METHODS: From August 2010 to 2014 August, 54 patients with displaced femoral neck fracture were treated with closed reduction and proximal cannulated screw locking plate fixation. There were 34 males and 20 females, aged from 18 to 55 years with an average of 39.8 years. The informations of fracture healing and complications were recorded after operation. According to Harris criteria, the function of hip joint was evaluated. RESULTS: All patients were followed up from 4 to 24 months with an average of 11.3 months. Three cases occurred fracture nonunion, fracture union rate was 94.4%(51/54), union time was from 3 to 6 months with an average of 4.1 months. Among the healed 51 cases, the median of femoral neck shorten was 0.8 mm with the mean of (0.48±0.46) mm. No complications such as infection, internal fixation displacement were found during follow up. According to Harris criteria, 40 cases obtained excellent results, 9 good, 2 fair, 3 poor. CONCLUSIONS: Close reduction and proximal femoral locking plate fixation is an effective method in treating femoral neck fracture in young adults, it has advantages of avoiding the femoral neck crispation, reliable fixation, high rate of fracture union and good functional recovery.

Prevalence of dysphagia in multiple sclerosis: a systematic review and meta-analysis.

Although dysphagia was recognized as a clinical finding in multiple sclerosis (MS) as early as 1877, it has not received enough attention yet. With the progress of diagnostic method for dysphagia, there has been a rapid development in estimating the prevalence of deglutition disorder in MS. In this review, we aimed to conduct a systematic review and meta-analysis of published literature to establish the prevalence of dysphagia in multiple sclerosis. We systematically searched Embase, PubMed databases and Cochrane library from 1980 to August 2014, supplemented by hand searching to identify relevant studies. We used random-effects model to calculate pooled prevalence. Potential sources of heterogeneity were explored using sensitivity test and subgroup analysis, meta-regression analysis. Of 198 retrieved articles, 15 eligible surveys with a total population of 4,510 met the criteria. Twelve studies provided an estimate based on subjective screening test, which proved substantial heterogeneity (Cochran's χ(2) significant at p < 0.0001; I(2) = 92.4 %, 95 % CI 31-42 %), with a combined prevalence estimate of 36 %. Four studies provided an estimate based on objective measurements (clinical or instrument tools), which were substantial heterogeneity (Cochran's χ(2) significant at p < 0.005; I(2) = 77 %, 95 % CI 67-94 %), with a pooled prevalence estimate of 81 %. A large heterogeneity still existed after conducting several subgroup analyses and sensitivity tests. The findings confirm that more than one-third of the multiple sclerosis patients are suffering from swallowing difficulties. Therefore, we should be careful to interpret the pooled estimate due to the substantial heterogeneity between studies.

A novel antioxidant isobenzofuranone derivative from fungus Cephalosporium sp.AL031.

Bioassay-guided fractionation of metabolites from the fungus Cephalosporium sp.AL031 isolated from Sinarundinaria nitida led to the discovery of a new isobenzofuranone derivative, 4,6-dihydroxy-5-methoxy-7-methylphthalide (1), together with three known compounds: 4,5,6-trihydroxy-7-methyl-1,3-dihydroisobenzofuran (2), 4,6-dihydroxy-5-methoxy-7-methyl-1,3-dihydroisobenzofuran (3) and 4,5,6-trihydroxy-7-methylphthalide (4). The structure of the new compound 1 was determined based on MS, 1D and 2D NMR spectral data. Compounds 1-4 showed potent antioxidant activity with EC50 values of 10, 7, 22 and 5 µM by 1,1-diphenyl-2-picryhydrazyl (DPPH) radical-scavenging assay.