Efficacy of different courses of acupuncture for diarrhea irritable bowel syndrome: A protocol for systematic review and meta-analysis.

Irritable Bowel Syndrome (IBS) is the most common functional gastrointestinal disorder. As one of the most common subtypes of IBS, IBS-D can impair the patients' quality of life (QOL) and decreased work productivity. Acupuncture may be a potential treatment for patients with IBS-D. However, the treatment course of acupuncture was diverse. It is unclear what is the optimal acupuncture treatment courses for acupuncture. The efficacy and safety of different courses of acupuncture for IBS-D have not been systematically evaluated yet. The purpose of this study is to evaluate effectiveness of Acupuncture of different courses in the treatment of IBS-D and provide sufficient evidence for clinical recommendations for IBS-D. We will follow the Preferred reporting items for systematic reviews and meta-analysis protocols (PRISMA-P) guidelines to design the protocol of a systematic review and meta-analysis. This systematic review is registered in PROSPERO (CRD42023418846). We will include randomized controlled trials (RCTs) in which the efficacy of Acupuncture is compared with a placebo, sham acupuncture or Pinaverium bromide in the treatment of IBS-D with no language restrictions. The outcomes of interest will be efficiency rate and the Symptoms Severity Score. RCTs will be searched in the electronic database and Clinical Trials Registry Platform from inception to April 2023. Two independent reviewers will independently select studies, extract data from the included studies, and assess the risk of bias using the Cochrane tool. We will choose a random or fixed-effects model based on the heterogeneity index. We will use the relative risk and mean difference to estimate data with 95% CI. A stratified meta-analysis was conducted to evaluate the effect of different treatment courses of Acupuncture: 2weeks, 4weeks(or 1 months), 6 weeks, and 8 weeks. If there is significant clinical and methodological heterogeneity, we will look for the reason for heterogeneity and perform a subgroup analysis. According to the Grading of Recommendations Assessment, Development and Evaluation (GRADE), we will evaluate the evidence quality and provide the recommendation's strength.

Ginsenoside Rb1 stabilized and paclitaxel / protopanaxadiol co-loaded nanoparticles for synergistic treatment of breast tumor.

Ginsenosides are the major and key components for ginseng to exert its wide and beneficial therapeutic efficacy in clinic. Meanwhile, many ginsenosides and their metabolites showed in vitro an in vivo anti-tumor activity, among which ginsenoside Rb1 has attracted much attention due to its good solubility and amphipathy. In this study, the self-assembly behavior of Rb1 was investigated and the Rb1 nano-assembly could further stabilize or encapsulated hydrophobic drugs such as protopanaxadiol (PPD) and paclitaxel (PTX) to form nanoparticles, based on which, a natural nanoscale drug delivery system, ginsenoside Rb1 stabilized and PTX/PPD co-loaded nanoparticles (GPP NPs) were prepared. The resultant GPP NPs exhibited a small particle size of 126.2 nm, a narrow size distribution (PDI=0.145), and a zeta potential of -27.3 mV. PTX loading content was 11.06% with an encapsulation efficiency of 93.86%. GPP NPs were spherical and stable in normal saline, 5% glucose, PBS, plasma, or on-shelf storage for 7 days. Both PTX and PPD existed in an amorphous state in GPP NPs and were released in a sustained pattern. GPP NPs showed 10-fold higher in vitro anti-tumor activity of than PTX injections. In the in vivo experiment, GPP NPs achieved a much higher tumor inhibition rate than PTX injections (64.95% vs 43.17%, P < 0.01) and certain tumor target ability. In conclusion, GPP NPs had significantly enhanced anti-tumor efficacy and improved tumor microenvironment, thus were promising to be developed into a novel anti-tumor agent for the treatment of breast tumor.

Extracellular Vesicle-Mediated miR-150-3p Delivery in Joint Homeostasis: A Potential Treatment for Osteoarthritis?

BACKGROUND: The disruption of joint homeostasis is a critical event during the process of joint injury in osteoarthritis (OA). As regulatory molecules, microRNAs (miRNAs) can be released from secretory cells and delivered to recipient cells through extracellular vesicles (EVs), thereby playing an important role in regulating joint homeostasis. We hypothesized that the fibroblast-like synoviocytes (FLSs) in healthy joints could release EVs enriched in miRNAs that can maintain joint homeostasis by regulating the signal transduction pathways in the joints, whereby the articular cartilage (AC) is protected from degeneration, and OA progression is delayed. METHODS: Via high-throughput sequencing and qPCR, we found that miR-150-3p was enriched in the circulating EVs in healthy rats. Next, we established an in vitro cell model in which chondrocytes were cultured with (i) FLSs transfected with miR-150-3p mimics or (ii) EVs released by FLSs (FLS-EVs) inside the healthy synovial membrane (SM). The transportation mechanism from FLSs to chondrocytes was studied using the EV inhibitor GW4869, and the FLSs were transfected with a miR-150-3p mimic or inhibitor. To assess the therapeutic effect of miR-150-3p-carrying EVs (EVs-150) in vivo, healthy FLS-derived EVs (H-FLS-EVs) were injected into the tail vein of rats with OA at various stages of the pathogenesis and evaluated for the progression of OA. RESULTS: The chondrocytes could uptake fluorescent-labeled miR-150-3p mimics and FLS-EVs, and GW4869 suppressed this uptake. The overexpression of miR-150-3p could significantly reduce the concentrations of pro-inflammatory cytokines in the cell culture medium and the expression of the miR-150-3p target T cell receptor-interacting molecule 14 (Trim14), as well as the innate immune-related factors, including nuclear factor kappa B (NF-κB) and interferon-ß (IFN-ß). Similarly to the in vitro findings, the miR-150-3p level in the serum EVs was significantly upregulated among the EV-treated rats. In the AC of the OA rat model injected with H-FLS-EVs, the joint degeneration was suppressed, and Type II collagen (COLII) and aggrecan (ACAN) were significantly upregulated, whereas the innate immune-related factors Trim14, NF-κB, and IFN-ß were downregulated compared with the levels in the untreated OA rats. Notably, the suppression of joint degeneration was more significant when H-FLS-EVs were administered at the early stages of OA rather than the late stages. CONCLUSION: H-FLS-EVs protect chondrocyte function and maintain joint homeostasis by modulating the innate immune response by suppressing the Trim14/NF-κB/IFNß axis. These effects are achieved through the EV-mediated transport of miR-150-3p from the FLSs to the chondrocytes. Our findings show that EV-mediated miR-150-3p can be used to suppress OA, thus providing a novel therapeutic strategy. Additionally, the EV-mediated miR-150-3p transport may also serve as a potential biomarker in the diagnosis, treatment, and prognosis of OA.

Preparation of hydroxy genkwanin nanosuspensions and their enhanced antitumor efficacy against breast cancer.

Hydroxy genkwanin (HGK), a flavonoid compound from natural resources, showed good inhibition against the growth of breast tumor cells. However, the poor solubility restricted the further study and the in vivo drug delivery of HGK. We prepared HGK nanosuspensions by antisolvent precipitation method and investigated their characterization, stability, hemolysis probability, release behavior in vitro, antitumor activity in vitro and in vivo, and preliminary safety through acute toxicity experiments. The resultant HGK nanosuspensions (HGK-NSps) showed an average diameter of (261.1 ± 4.8 nm), a narrow particle size distribution (PDI of 0.12 ± 0.01), spherical morphology, high drug-loading content (39.9 ± 2.3%, w/w), and good stability in various physiological media. HGK-NSps was safe for intravenous injection at low concentration and HGK was slowly released from the obtained nanosuspensions. HGK-NSps showed stronger cytotoxicity than free HGK against many tumor cells in vitro. Especially against MCF-7 cells, the IC50 value was decreased to 1.0 µg/mL, 5-fold lower than the HGK solution. In the in vivo antitumor activity study HGK-NSps (40 mg/kg) displayed a similar therapeutic effect to that of the paclitaxel injection (8 mg/kg). The preliminary acute toxicity test showed that even at the highest dose of 360 mg/kg (iv), HGK-NSps had 100% of mice survival and all the mice were in a good state, suggesting a maximum tolerated dose more than 360 mg/kg. The effective antitumor effect and good tolerance showed HGK-NSps were likely to become a safe and effective antitumor drug for the treatment of breast cancer in the future.

Association of body mass index and blood lipid profile with cognitive function in Chinese elderly population based on data from the China Health and Nutrition Survey, 2009-2015.

AIM: The associations of body mass index (BMI) and serum lipids with cognitive function are inconsistent and remain unclear, especially in the elderly population. This discrepancy triggered our interest in exploring the impact of BMI and serum lipids on memory status among the elderly Chinese population. METHODS: Data were collected from the China Health and Nutrition Survey database. We used data from the survey's 2015 wave to examine the association between BMI and memory status and from the 2009-2015 surveys to examine the association between serum lipids and cognitive function. We performed multivariable logistic regression analyses and multivariable linear regression analyses to examine these associations. RESULTS: Being underweight, normal weight, and severely obese were associated with an increased risk of bad self-reported memory status, with overweight as the reference. After adjustment for confounding factors, BMI was positively associated with cognitive function score in the low BMI group (≤24.5 kg/m2 ) (ß ± SE: 0.02 ± 0.01, P = 0.013) and negatively associated with cognitive function score in the high BMI group (>24.5 kg/m2 ) (ß ± SE: -0.04 ± 0.01, P = 0.009) in multivariable linear regression analysis. In men, higher levels of serum triglycerides and apolipoprotein B were associated with a decreased risk of cognitive impairment. In women, a higher level of high-density lipoprotein cholesterol was associated with a decreased risk of cognitive impairment. CONCLUSION: We found inverse U-shaped relationships between BMI and cognitive function and for the gender-specific association of serum lipids with cognitive function. This result indicated that among the elderly population, better nutritional status suggests superior memory status and cognitive function performance.

Long noncoding antisense RNA FAM83A-AS1 promotes lung cancer cell progression by increasing FAM83A.

The abnormal expression of long noncoding RNAs (lncRNAs) is closely associated with human cancers. As one special group of lncRNAs, natural antisense transcripts (NATs) can be transcribed from both DNA strands at the same locus but in the opposite direction from the gene transcript. Their expression levels are altered in many cancers, but their roles are poorly understood. We strove to find NATs involved in human non-small-cell lung cancer (NSCLC) and to reveal their mechanism of action in cancer. We analysed the NATs in NSCLC from the TCGA database by circlncRNAnet. One NAT, family with sequence similarity 83 member A antisense RNA 1 (FAM83A-AS1), was found to be markedly upregulated and positively correlated with its cognate sense counterpart, FAM83A, in NSCLC. Moreover, overexpression of FAM83A-AS1 increased FAM38A protein levels and induced ERK1/2 phosphorylation downstream of FAM83A in cells. Finally, overexpression of FAM83A-AS1 promoted LUAD cell proliferation and invasion. In summary, lncRNA FAM83A-AS1 promotes LUAD by increasing FAM83A expression.

[Correlation of genes expression on MyD 88-dependent signaling pathway in progression of knee osteoarthritis].

OBJECTIVE: To investigate expression features and correlation of genes expression on MyD88-dependent signaling pathway in synovial membrane (SM) of progression of knee osteoarthritis (OA). METHODS: Sixty Wistar rats were randomly divided into 6 groups, including blank group (N), false surgical group, model groups[2 weeks (2W), 4 weeks (4W), 8 weeks (8W) and 12 weeks (12W)], with 10 rats in each group. The models were established by using Hulth method. Control group was experienced no surgery, while false surgical group was only opened joint cavity and sutured. The SM samples was collected according to the time designed above. The relative expression quantity of MyD88, TLR4 and NF-κB was detected by Real-time PCR after the extraction of the total RNA and reverse transcription. The correlation analysis was obtained by SPSS. RESULTS: There was no significant difference in each gene mRNA expression between false surgical and blank group(P> 0.05), while enhanced expression was found in the model groups(P<0.05). The correlation index among MyD88, TLR4 and NF-κB was 0.91 and 0.86 respectively, and had significant difference among them. CONCLUSIONS: Positively relative among MyD88, TLR4 and NF-κB played main role in TLR4/NF-κB signal passway, and could predicate the expression of other genes in the passway. It also could further provide the basis for clarify the pathologic mechanism of knee OA.

[Impacts of acupoint catgut embedding therapy on postpartum weight retention].

OBJECTIVE: To observe the impacts of acupoint catgut embedding therapy on postpartum weight retention. METHODS: Seventy-one women of postpartum weight retention were divided into an observation group (35 cases) and a control group (36 cases) according to their own wishes when re-examination in 42 days after delivery. In the control group, the nutrition consultation was provided and the calories intake was controlled continuously for 20 weeks. In the observation group, on the basis of the treatment as the control group, the acupoint embedding therapy was applied to Zhongwan (CV 12), Zhongji (CV 3), Qihai (CV 6), Guanyuan (CV 4), Tianshu (ST 25), Guilai (ST 29), Shuifen (CV 9), Shousanli (LI 10), Zusanli (ST 36), Fenglong (ST 40) and Yinlingquan (SP 9). The sutures, No. 4-0 were cut as 2 to 4 mm in length and put into the embedding needle. After qi arrival, the sutures were pushed into the acupoints with the needle core and the needle was removed quickly. The treatment was given once every two weeks, continuously for 20 weeks. Totally, 10 times of acupoint catgut embedding therapy were required. Before and after treatment, the body mass, weight retention, body mass index (BMI), percentage of body fat (PBF), waist circumference (WC), waist-hip ratio (WHR) and health promoting lifestyle profile (HPLP-Ⅱ) were observed in the participants of the two groups. RESULTS: After treatment, body mass, weight retention, BMI, PBF, WC and WHR were all reduced as compared with those before treatment in the participants of the two groups, indicating the significant differences (all P<0.05). After treatment, the body mass, weight retention, BMI, PBF, WC and WHR in the participants of the observation group were lower than those in the control group, indicating the significant differences (all P<0.05). The score of every dimension of HPLP-Ⅱ after treatment was higher than that before treatment in the participants of the observation group, indicating the significant differences (all P<0.05); and the scores of health responsibility, sports and spiritual growth in the observation group were higher than those in the control group, indicating the significant differences (all P<0.05). CONCLUSIONS: The acupoint catgut embedding therapy improves in the postpartum weight retention and achieves the satisfactory clinical therapeutic effects.

[Effect of Acupuncture Therapy on Body Compositions in Patients with Obesity].

OBJECTIVE: To observe the clinical effectiveness of acupuncture intervention in weight reduction by modulating body compositions in obesity patients. METHODS: A total of 71 obesity patients during weight-loss procedure were allocated to acupuncture+nutrition-consultation group (n=40) and simple nutrition-consultation group (n=31). The patients of the acupuncture +nutrition-consultation group were treated by acupuncture stimulation of Zhongwan (CV 12), Xiawan (CV 10), Tianshu (ST 25), Wailing (ST 26), Qihai (CV 6), Guanyuan (CV 4), etc. for 30 min, once every other day, 3 times per week, 12 times altogether, and also given with weekly nutrition consultation (including subjective query, objective measurement, analysis, program for nutrition support) at the same time. The patients of the simple nutrition-consultation group were treated by only weekly nutrition consultation for 4 weeks. Before and after the treatment, the patients' body weight, body mass index (BMI), fat mass, percentage of body fat, muscle mass, protein quality, water quality and bone mass were measured by using a composition analyzer. RESULTS: After 4 weeks' treatment, the body mass, BMI, fat mass and fat percentage in both acupuncture+nutrition-consultation and simple nutrition-consultation groups were significantly decreased (P<0.01), while the weight levels of muscle, protein, bone and water content had no apparent changes (P>0.05). The therapeutic effect of acupuncture+nutrition-consultation group was markedly superior to that of the simple nutrition-consultation group in increasing the improved degrees of body weight, BMI, fat mass and fat percentage (P<0.01). CONCLUSIONS: Acupuncture plus nutrition consultation is effective in reducing body mass, fat mass and percentage of body fat in obesity patients.

[Effect of Acupuncture Therapy in Combination with Nutrition Control on Body-weight Reduction in Postpartum Obesity Subjects].

OBJECTIVE: To observe the clinical effect of acupuncture therapy in the treatment of postpartum obesity subjects. METHODS: A total of 71 postpartum obesity subjects were allocated to treatment group (n=35) and control group (n=36). Participants of the control group were asked to receive weekly nutrition consultation (body-weight management) for calorie intake control during 4 weeks' treatment, and those of the acupuncture group were treated by manual acupuncture stimulation of Zhongwan (CV 12), Zhongji(CV 3), Qihai(CV 6), Shuifen (CV 9), and Guanyuan (CV 4), bilateral Tianshu (ST 25), Guilai (ST 29), Shousanli (LI 10), Zusanli (ST 36), Fenglong (ST 40), and Yinlingquan (SP 9) in combination with nutrition consultation. The treatment was conducted once every other day, continuously for 4 weeks. The body weight(BW), body mass index (BMI), percent of body fat (PBF) and waist-to-hip ratio (WHR) were determined before and after the treatment. RESULTS: After the treatment, the BW, BMI, PBF and WHR in the acupuncture group, and the BW and WHR in the control group were significantly decreased (P<0.01, P<0.05), and the therapeutic effect of the acupuncture group was notably superior to that of the control group in reducing BW and WHR (P<0.05, P<0.01). CONCLUSIONS: Acupuncture therapy combined with nutritional calorie control has a positive role in relieving obesity in postpartum obesity participants.

[Effect of Electroacupuncture Intervention on Behavior Changes and Levels of Hippocampal Transforming Growth Factor beta 3 and Basic Fibroblast Growth Factor Proteins in Depression Rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on behavior changes and the adundance levels of transforming growth factor beta 3 (TGF-beta 3) and basic fibroblast growth factor (bFGF) proteins in the hippocampus of rats with chronic unpredictable mild stress (CUMS)-induced depression, so as to explore its mechanisms underlying improvement of depression. METHODS: Forty Sprague-Dawley rats were randomly divided into the following groups: control, model, EA, and medication (Fluoxetine), n = 10 in each group. The depression model was established by CUMS combined with solitary raising for 28 days. EA (2 Hz, 0.6 mA) was applied to "Baihui" (GV 20) and "Yintang" (GV 29) for 20 mm, once daily before CUMS every day. The rats of the medication group were given with Fluoxetine (10 mg/kg, 5 mL/kg) before CUMS every day. The behavioral changes (crossing and rearing locomotion) were detected by using open field tests. The expression levels of TGF-beta 3 and bFGF proteins of the bilateral hippocampus tissues were detected using biotin label-based antibody protein chips. Results Compared to the control group, the crossed grid-square numbers and rearing times were significantly decreased in the model group (P<0.01). Following EA and medication interventions, the CUMS induced decreases of the crossed grid-square number and rearing times were notably reversed in both EA and medication groups (P<0.01), suggesting an amelioration of depression after the intervention. The relative expression level of hippocampal TGF-beta 3 was down-regulated (fold change = 0.48, vs. the control group) and that of bFGF up-regulated (fold change= 1.36, vs the control group) in the model group. In both the EA and medication groups, the down-regulated TGF-beta 3 expression and the up-regulated bFGF protein expression were suppressed (TGF-beta 3: fold change = 1.61, 1.6 and bFGF: fold change = 0.61, 0.45, vs. the model group respectively). CONCLUSION: EA can improve the depression-like state in depression rats which may be associated with its effect in up-regulating hippocampal TGF-beta 3 protein level and down-regulating bFGF protein expression via promoting neurogenesis.

[Effect of Acupuncture Stimulation of Different Acupoint Groups on Levels of Stress Hormones and Serum Brain-derived Neurotrophic Factor in Depression Rats].

OBJECTIVE: To screen the effective acupoints for anti-depression in depression rats and to explore the mechanisms of acupuncture for relieving depression. METHODS: Fifty rats were randomly divided into normal control, model, "Yin-tang" (EX-HN 3)-"Baihui" (GV 20, 2-acupoints), EX-HN 3-GV 20-"Fengchi" (GB 20)-"Shenshu" (BL 23, 4-acupoints) and medication groups, with 10 rats in each group. The depression model was established by unpredictable chronic mild stress (UCMS) for 28 days. For rats of the 2-acupoints and 4-acupoints groups, EX-HN 3 and GV 20, and EX-HN 3, GV 20, GB 20 and BL 23 were punctured with filiform needles respectively before performing mild stress every time. The acupuncture needles were retained for 30 min during each intervention and the treatment was conducted once daily for 28 days. The rats of the medication group were treated by intragastric administration of Fluoxetine (0.18 mg/kg) once a day for 28 days. The rats' anxiety-like behavior (rearing and crossing times) was detected by open-field test. The contents of adrenocorticotropic hormone (ACTH) in the pituitary, 5-hydroxytryptamine (5-HT) in the hippocampus, the cortisol (CORT) in the adrenal gland, and the brain derived neurotrophic factor (BDNF) in the serum were examined by ELISA. RESULTS: Compared to the normal control group, the numbers of both rearing and crossing motions in the model group were significantly decreased (P<0.01, P<0.05), while in comparison with the model group, the rearing and crossing numbers of rats in the 2-acupoints and 4-acupoints and medication groups were significantly increased (P<0.01). ELISA showed that after modeling, the content of adrenal CORT was significantly increased (P<0.01), and those of hippocampal 5-HT and serum BDNF were obviously down-regulated in the model group (P<0.01). After the treatment, the adrenal CORT levels in the three intervention groups were notably down-regulated, and hippocampal 5-HT and serum BONE evidently up-regulated in these 3 intervention groups (P<0.05, P<0.01). No marked changes were found in the pituitary ACTH contents of the model and 3 intervention groups (P>0.05), and no significant differences were shown among the three intervention groups in the levels of the aforementioned 6 indexes (P>0.05). CONCLUSION: Acupuncture intervention can effectively improve the unprompted activates of the depression rats, which may be related to its effects in up-regulating hippocampal 5-HT and serum BONE levels, and in down-regulating adrenal CORT content.

The potential role of IGF-I receptor mRNA in rats with diabetic retinopathy.

OBJECTIVE: To evaluate the potential role of insulin-like growth factor-1 receptor mRNA (IGF-IR mRNA) in the onset and development of retinopathy in diabetic rats. METHODS: A diabetic model was duplicated in Wistar rats. The early changes in the retina were examined using light and transmission electron microscopy. Expression of IGF-IR mRNA was analyzed using in situ hybridization. RESULTS: Weak expression of IGF-IR mRNA (5%) was found in retinas of normal rats, but was significantly increased (15% and 18%) in the retinas of diabetic rats after 3 and 6 months of diabetes (P < 0.01). In situ hybridization and morphological study demonstrated that there was a positive correlation between IGF-IR mRNA expression and retinal changes at various stages. CONCLUSION: Increased IGF-IR mRNA might play an important role in the onset and development of diabetic retinopathy.