Using Functionalized Liposomes to Harvest Extracellular Vesicles of Similar Characteristics in Dermal Interstitial Fluid.

Extracellular vesicles (EVs) are used by living cells for the purpose of biological information trafficking from parental-to-recipient cells and vice versa. This back-and-forth communication is enabled by two distinct kinds of biomolecules that constitute the cargo of an EV: proteins and nucleic acids. The proteomic-cum-genetic information is mediated by the physiological state of a cell (healthy or otherwise) as much as modulated by the biogenesis pathway of the EV. Therefore, in mirroring the huge diversities of human communications, the proteins and nucleic acids involved in cell communications possess seemingly near limitless diversities, and it is this characteristic that makes EVs so highly heterogeneous. Currently, there is no simple and reliable tool for the selective capture of heterogeneous EVs and the delivery of their undamaged cargo for research in extracellular protein mapping and spatial proteomics studies. Our work is a preliminary attempt to address this issue. We demonstrated our approach by using antibody functionalized liposomes to capture EVs from tumor and healthy cell-lines. To characterize their performance, we presented fluorescence and nanoparticle tracking analysis (NTA) results, TEM images, and Western blotting analysis for EV proteins. We also extracted dermal interstitial fluid (ISF) from healthy individuals and used our functionalized synthetic vesicle (FSV) method to capture EVs from their proteins. We constructed three proteomic sets [EV vs ISF, (FSV+EV) vs ISF, and (FSV+EV) vs EV] from the EV proteins and the free proteins harvested from ISF and compared their differentially expressed proteins (DEPs). The performance of our proposed method is assessed via an analysis of 1095 proteins, together with volcano plots, heatmap, GO annotation, and enriched KEGG pathways and organelle localization results of 213 DEPs.

The efficacy and safety of simple-needling for the treatment of primary dysmenorrhea compared with ibuprofen: A systematic review and meta-analysis.

BACKGROUND: Needling and ibuprofen are often used clinically to treat primary dysmenorrhea (PD). However, the difference between the efficacy and safety of the treatment of PD is not clear. This study evaluates the efficacy and safety of simple-needling for PD patients through a comparison with ibuprofen. METHODS: A comprehensive search of 7 electronic databases and relevant medical journals, from the establishment of the publication to December 2020. The Cochrane risk of bias tool was used to evaluate the methodological quality of randomized clinical trials (RCTs) that met the inclusion criteria, and a meta-analysis was performed with the Review Manager version (RevMan version 5.3). RESULTS: Twenty three RCTs were included. The meta-analysis reported that simple-needling groups had better than ibuprofen groups on cure rate (relative risk = 2.29, 95% CI [1.96, 2.68], P < .00001) and total effective rate (relative risk = 1.24, 95% CI [1.19, 1.29], P < .00001) and VAS score (MD = -1.24, 95% CI [-1.92, -0.55], P = .0004). Seven studies reported adverse events, of which 4 studies had mild adverse events. CONCLUSION: Simple-needling is superior to ibuprofen treatment in terms of clinical efficacy and improvement of pain symptoms. A small number of studies reported whether simple-needling produced adverse events, so there is not enough evidence to support the safety of simple-needling in the treatment of PD. PROSPERO REGISTRATION NUMBER: CRD42021233403.

Platelet rich plasma versus glucocorticoid for plantar fasciitis: A protocol for systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Plantar fasciitis (PF) is the most common cause of heel pain in adult. There are a variety of ways to treat PF, but these treatments have varied result in their effectiveness, and exist different degrees of limitations. At present, clinical studies focus on the effect of glucocorticoid (GC) and platelet rich plasma (PRP) in the treatment of PF, but there is a lack of systematic evaluation PRP and GC's clinical effect towards PF. This study aims to evaluate the long-term efficacy of GCs and PRP in the treatment of PF by means of meta-analysis. METHODS: The literature of a randomized controlled clinical trial of PRP in the treatment of plantantifasciitis was searched on the Internet. Retrieve 7 databases. EndNote X9 software was used for document management. The Jadad scale was used to score the literature. Risk assessment of the literature was conducted according to Cochrane's systematic evaluation manual 5.0. RevMan5.3 software was used for literature risk bias analysis. Stata12.0 software is used for sensitivity analysis. RESULTS: This study will provide effective evidence-based evidence for the long-term efficacy of PRP and GC in treating PF. CONCLUSION: A systematic review and meta-analysis were conducted for the comparison of the long-term effect of PRP and GC on plantar fascia in the treatment of PF.

[Clinical observation on the distribution characteristics and rules of pressing sensitive acupoints in bronchial asthma patients].

OBJECTIVE: To compare the distribution characteristics of pressing sensitive acupoints on the body surface between bronchial asthma (BA) patients and healthy subjects, and to analyze the distribution rules of pressing sensitive acupoints in BA patients. METHODS: Seventy BA patients and 70 healthy subjects were selected in this study. The pressing sensitive acupoints were checked with finger pulp and marked on human nerve segment graph. The numbers of pressing sensitive acupoints were counted and the positional relationship between distribution of pressing sensitive acupoints and the position of meridians and nerve segment was observed. RESULTS: (1) The incidence rates of pressing sensitive acupoints in BA patients group and healthy subjects group were 91.4% (64/70) and 15.7% (11/70) respectively, and the BA patients group was higher than the healthy subjects group (P<0.01). (2) The top 3 meridians with pressing sensitive acupoints occuring in BA patients were bladder meridian of foot-taiyang, lung meridian of hand-taiyin and large intestine meridian of hand-yangming, and the most frequent pressing sensitive acupoints were Feishu（BL 13）, Xinshu（BL 15）, Chize（LU 5） and Jueyinshu (BL 14). (3) The pressing sensitive acupoints in BA patients were distributed mainly on C4, C6 and T1-T6 nerve segment. CONCLUSION: Pressing sensitive acupoints have a close correlation with physical condition, and there is a close relation between pressing sensitive acupoints distribution and corresponding meridians and nerve segments in BA patients.

[Correlation between referred pain distribution and acupoint sensitization in patients with intestinal diseases].

OBJECTIVE: To observe the correlation between referred pain distribution and acupoint sensitization in patients with intestinal diseases. METHODS: In clinical research, 443 patients from 8 hospitals were recruited, including the outpatients and inpatients of Crohn's disease (n=143), ulcerative colitis (n=108), chronic appendicitis (n=87) and other intestinal diseases (n=105). The site with tenderness on the body surface and the morphological changes of local skin were observed and recorded in the patients. Using a sensory tenderness instrument, the pain threshold at the sensitization point was measured in 60 patients with ulcerative colitis. In animal experiment, SD rats were used and divided into a enteritis group (n=8), in which the enteritis model were established, and a control group (n=3), in which no any intervention was given. After the injection of Evans blue (EB) at caudal vein, the blue exudation points on the body surface were observed and the distribution rule was analyzed statistically. RESULTS: The referred pain on the body surface in the patients with intestinal diseases was mainly located in the lower abdomen (93.9%, 416/443), the lumbar region (70.9%, 314/443) and the lower legs (33.0%, 146/443). The diameter of tenderness region was 1.5 to 2.5 cm. Compared with the region without sensitization, the pain threshold of the sensitization point in the patients with ulcerative colitis was reduced significantly (P<0.001). The referred pain on the body surface in the patients with appendicitis was located in the right lower abdomen (97.7%, 85/87), the waist and back (54.0%, 47/87) and the right lower limbs on the medial side (71.3%, 62/87). The tenderness region was 1 to 2 cm in diameter and was irregular in form. After modeling of enteritis in the rats, the EB exudation points were visible from T12 to L2. CONCLUSION: Intestinal diseases induce referred pain on the body surface where is the same as or adjacent to the location of the spinal segment corresponding to the affected intestinal section. These sensitization regions are related to the locations of acupoints.

[Distributive regularity of pressing sensitive acupoints in chronic non-atrophic gastritis patients].

OBJECTIVE: To compare the distribution regularity of the pressure-sensitive acupoints in patients with chronic non-atrophic gastritis (CNAG) and healthy subjects, so as to provide suitable acupoint combinations for clinical treatment. METHODS: A total of 120 volunteer subjects including 60 CNAG patients (29 men and 31 women, (40.7±10.3) years at the average age) and 60 healthy subjects (28 men and 32 women, and (40.8±10.2) years at the average age) were enrolled in the present study. The pressure-sensitive acupoints were checked by a fixed operator using his finger pulp along the body trunk and the four limbs and marked on a prepared human dermatome graph. The number of pressing sensitive acupoints were counted, and the relationship between the distribution of the detected sensitive acupoints and the position of meridians and nerve segments was analyzed. RESULTS: The incidence of pressure-sensitive acupoint in CNAG patients and healthy subjects were 86.7% and 15.0%, respectively. In 60 CNAG patients, the most frequently met sensitive acupoints were Xuehai (SP10), Zhongwan (CV13), and Zhongting (CV17) in sequence, mainly covering the Conception Vessel, Spleen Meridian of Foot-Taiyin (SP), and the Stomach Meridian of Foot-Yangming (ST). The sensitive acupoints presented a nerve-segmental distribution within T7-T10 and L3-L5. CONCLUSION: The pressure-sensitive acupoints present a nerve-segmental distribution and have a higher corresponding rate with some meridians related to the stomach, especially under diseased conditions.

Efficacy and safety of moxibustion in patients with chronic prostatitis/chronic pelvic pain syndrome: A systematic review protocol.

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common urogenital disease. Moxibustion is a complementary treatment option for CP/CPPS. This systematic review will assess the efficacy and safety of moxibustion as a sole or add-on therapy for CP/CPPS. METHODS: We will retrieve randomized controlled trials (RCTs) of moxibustion for CP/CPPS from the following databases: PubMed, EMBASE, Cochrane Central Register of Controlled Trials, VIP, Chinese Biomedical Database, China National Knowledge Infrastructure Database, Wanfang Data, Chinese Medicine Database System, Google Scholar, Clinicaltrials.gov, and China Clinical Trial Registry from their inception to March 9, 2019, without language restrictions. RCTs comparing moxibustion with active drugs or moxibustion + drugs with these same drugs alone will be included. Primary outcomes will be the change in the total score of the National Institutes of Health's Chronic Prostatic Inflammatory States Index (NIH-CPSI) after moxibustion treatment. Secondary outcomes will include the scores of the individual NIH-CPSI domains, response to treatment of CP/CPPS, leucocyte and phosphatidylcholine corpuscle count in prostatic fluid, incidence of adverse events (AEs), and incidence of moxibustion-related AEs. The Cochrane risk of bias tool will be used for evaluating the risk of bias of individual trials. Heterogeneity will be detected by the Cochran Q test and I-square test. A random-effects model will be used to pool data in the meta-analysis. Risk ratio and weighted or standardized mean difference will be used as the effect measures. Three sets of subgroup analyses will be performed to explore the sources of heterogeneity. Where appropriate, we will assess the likelihood of publication bias based on funnel plots and quantitative tests. RESULTS: This study will produce the systematic review evidence regarding moxibustion for treating CP/CPPS based on current RCTs. CONCLUSION: This study will provide a clear basis for understanding the efficacy and adverse reactions of moxibustion treatment for CP/CPPS. PROSPERO REGISTRATION NUMBER: CRD42019121338.

[Correlation Between Referred Pain Region and Sensitized Acupoints in Patients with Stable Angina Pectoris and Distribution of Sensitized Spots in Rats with Myocardial Ischemia].

OBJECTIVE: To observe the correlation between the referred pain regions of stable angina pectoris (SAP) and the acupoints in coronary heart disease (CHD) patients and to investigate the rule of regional sensitized point distribution in rats. METHODS: A total of 1 046 CHD patients with SAP from 8 hospitals in China were recruited in the present study. The tenderness was palpated along the left and right chest, back, shoulder, upper limb, etc. by a specially-assigned researcher in each hospital. Among them, 77 patients accepted pain threshold (PT) measurement by using a hand-held esthesiometer. In animal experiments, 14 SD rats were subjected to occlusion of the left anterior descending branch of the left coronary artery for 4 h for establishing myocardial ischemia (MI) model, and other 4 normal rats were used as the sham-operation control group. Four hours after MI, all the rats accepted tail venous injection of 5% Evans blue (50 mg/kg) for examining the distribution of the blue dye exudation spots at the body surface where the mechanical PT was also detected by a von Frey. RESULTS: In 1 046 CHD patients, 987 (94.36%) were found to have at least one tenderness spot. The tenderness spots were found at the left chest (87.47%), right chest (13.67%), left arm (ulnar side, 41.30%), right upper limb (4.68%), left shoulder back (30.21%), right shoulder back (7.07%), etc., accompanied with rash or pigmentation, subcutaneous induration, cord-like tissue contracture, skin sag, etc. The mechanical PT level was significantly lower at the tenderness spots of the left upper limb than at non-tender points of the right upper limb in CHD patients (P<0.001). Tenderness and cutaneous abnormal changes in angor pectoris patients distributed mostly on the left chest, back, shoulder and upper limb, and some also on the right. Tender points scattered on, near or outside acupoints. A similar distribution of the blue exudation spots and lower mechanical PT spots were found in MI rats, but not in sham-MI rats. CONCLUSION: In the case of MI, a regular "referred sensitization" response frequently occurs in the dermatomere area innervated by the corresponding segments (T 1－T 5) in both CHD patients and MI rats, which may be closely associated with the formation of acupoints in ancient China.