RNA m6A dynamic modification mediated by nucleus-localized FTO is involved in follicular reserve.

In eukaryotic organisms, the most common internal modification of messenger RNA (mRNA) is N6-methyladenosine (m6A). This modification can be dynamically and reversibly controlled by specific enzymes known as m6A writers and erasers. The fat-mass and obesity-associated protein (FTO) catalyzes RNA demethylation and plays a critical role in various physiological and pathological processes. Our research identified dynamic alterations in both m6A and FTO during the assembly of primordial follicles, with an inverse relationship observed for m6A levels and nuclear-localized FTO expression. Application of Fto small interfering RNA (siRNA) altered the expression of genes related to cell proliferation, hormone regulation, and cell chemotaxis, and affected RNA alternative splicing. Overexpression of the full-length Fto gene led to changes in m6A levels, alternative splicing of Cdk5, cell proliferation, cell cycle progression, and proportion of primordial follicles. Conversely, overexpression of Fto lacking a nuclear localization signal (NLS) did not significantly alter m6A levels or primordial follicle assembly. These findings suggest that FTO, localized in the nucleus but not in the cytoplasm, regulates RNA m6A demethylation and plays a role in cell proliferation, cell cycle progression, and primordial follicle assembly. These results highlight the potential of m6A and its eraser FTO as possible biomarkers and therapeutic targets.

The efficacy of Yiqi Huoxue method in treating coronary artery disease after percutaneous coronary intervention: A meta-analysis in accordance with PRISMA guideline.

BACKGROUND: Percutaneous coronary intervention (PCI), the most common method in treating coronary artery disease (CAD), has a variety of side effects. Yiqi Huoxue therapy (YQHX) can effectively alleviate the symptoms of patients and reduce the side effects. However, a reliable and systematic assessment of the methodologies is not available. METHODS: Seven electronic databases were searched to identify randomized controlled trials of YQHX method for CAD after PCI. The quality assessment of the trials included was performed by employing the Cochrane Risk of Bias tool. RESULTS: One thousand eight hundred sixty-eight patients from 23 randomized controlled trials were included in this review. The aggregated results showed that the experimental group got better effect in increasing ORR, TCMSRR, ECG, HDL-C, and in lowering the level of CRP, TC, and MACE in comparison with the control group. CONCLUSION: YQHX method is a valid complementary and alternative therapy in the management of CAD after PCI, and is an effective and safe therapy for CAD.

Gut microbiota and diabetic kidney diseases: Pathogenesis and therapeutic perspectives.

Diabetic kidney disease (DKD) is one of the major chronic complications of diabetes mellitus (DM), as well as a main cause of end-stage renal disease. Over the last few years, substantial research studies have revealed a contributory role of gut microbiota in the process of DM and DKD. Metabolites of gut microbiota like lipopolysaccharide, short-chain fatty acids, and trimethylamine N-oxide are key mediators of microbial-host crosstalk. However, the underlying mechanisms of how gut microbiota influences the onset and progression of DKD are relatively unknown. Besides, strategies to remodel the composition of gut microbiota or to reduce the metabolites of microbiota have been found recently, representing a new potential remedial target for DKD. In this mini-review, we will address the possible contribution of the gut microbiota in the pathogenesis of DKD and its role as a therapeutic target.

Exploration of Adherence to the Immunosuppressive Medication in Kidney Transplant Recipients Based on Theory of Planned Behavior.

To investigate adherence to immunosuppressive medication (IM) in kidney transplant recipients (KTRs) and analyze the associated factors using the Theory of Planned Behavior (TPB). Data were collected at Time1 (T1) and 3 months later (T2). T1: the elements of the TPB, past behavior, beliefs about medicines, perceived social support were measured. T2: IM adherence was measured. Structural equation modeling was applied to analyze the associated factors of medication adherence. A total of 246 KTRs were included. The average IM adherence score of KTRs' was 4.86 (SD = 1.63). Of the recipients, 39.43% had one aspect of non-adherence to IM. The model could explain 28.7% of the variance in adherence to IM (R2 = .287, p = .006). TPB is a useful tool for understanding adherence to IM in KTRs. Caregivers can provide effective interventions during follow-up, which should focus on improving medication beliefs as well as provision of other external support especially from outside.

Adverse Effects of Andrographolide Derivative Medications Compared to the Safe use of Herbal Preparations of Andrographis paniculata: Results of a Systematic Review and Meta-Analysis of Clinical Studies.

Background and objective: Andrographis paniculata (AP) is a traditionally used herbaceous plant, whose main active constituent is andrographolide. Andrographolide derivative medications and herbal preparations of AP are often used to treat respiratory tract infections. This study aims to systematically evaluate the safety of andrographolide derivative medications and herbal preparations of AP based on clinical studies. Methods: English and Chinese databases were searched for all types of clinical studies that reported adverse drug reactions (ADRs) and adverse events (AEs) of andrographolide derivative medications and herbal preparations of AP. The ADRs and AEs were classified according to manifestations, and graded according to severity. Single-rate meta-analysis was performed for ADR incidence using R software. Results: A total of 262 studies were included, including 125 randomized controlled trials, 23 non-randomized controlled trials, 6 case series, and 108 case reports. In 9490 participants using andrographolide derivative injections, 383 (4.04%) reported ADRs. Meta-analysis showed that the ADR incidence of three most frequently used injections of andrographolide derivatives (andrographolide sulfonate, potassium sodium dehydroandrographolide succinate, and potassium dehydroandrographolide succinate) were 5.48% [95% CI (4.47%, 6.72%)], 3.69% [95% CI (2.59%, 4.94%)] and 5.33% [95% CI (3.68%, 7.72%)], respectively, which may be slightly higher than the actual ADR incidence, because only studies that reported the occurrence of ADRs or AEs were included, but studies without ADR and AE were not included. The ADRs of andrographolide derivative injections were mainly gastrointestinal, skin and subcutaneous tissue disorders, and anaphylaxis. Fifty-five patients experienced life-threatening anaphylactic shock, three patients died, and the causation attributed to the andrographolide derivative injection. Other ADRs were mild, moderate or medically significant. Nine herbal preparations of AP were tested in 10 studies, and the reported ADRs were mainly mild to moderate gastrointestinal, skin and subcutaneous tissue disorders. Except for five patients using andrographolide derivative injections eventually died, most of the ADRs were alleviated after drug withdrawal and symptomatic treatment. Conclusions: The ADRs of andrographolide derivative medications are few, but can be life-threatening, mainly gastrointestinal, skin and subcutaneous tissue disorders, and anaphylaxis. Injections of andrographolide derivatives should be used with caution. Herbal preparations of AP are essentially safe. Systematic Review Registration: [website], identifier [registration number].

Chinese herbal medicine for myasthenia gravis: A systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Myasthenia Gravis (MG) is a disorder of neuromuscular transmission bringing mild ocular weakness to severe generalized muscle weakness and disability. The conventional treatments have long-term side effects, and Chinese herbal medicines (CHM) have shown possible effect and safety for MG patients, but the existing evidence was not robust enough and the results were out of date. METHODS: Searching for randomized controlled trials (RCTs) was conducted in 7 databases and clinical trial registries until July 2021. The ROB 2 tool was used to assess the study quality and GRADE was used to assess the quality of whole evidence. Meta-analyses were conducted and the results were presented as risk ratio (RR) or mean difference (MD) with 95% confidence interval (CI). RESULTS: Nineteen RCTs (1283 participants) testing 13 kinds of CHM with adequate randomization were included and six RCTs investigating Compound Huangqi were included in the meta-analyses. In addition to conventional treatment, nine CHMs reduced symptom scores of MG. Compound Huangqi plus conventional treatment (pyridostigmine bromide or prednisone or both) reduced the symptom scores compared with conventional treatment (MD = -3.56, 95%CI -4.86 to -2.26). Less adverse events happened in the CHM groups (3/247 in the CHM groups, 52/245 in the control groups, RR = 0.13, 95%CI 0.06 to 0.30, 9 RCTs, a total of 492 participants). The effect on quality of life was inconsistent. CONCLUSION: Nine CHMs could probably bring benefit for MG symptom improvement. Moderate to low certainty of evidence supported Compound Huangqi added-on conventional treatment probably bring extra benefit of improving MG symptoms. Adding CHMs could be safer than giving only conventional treatment. STUDY REGISTRATION: The protocol was registered in PROSPERO (ID: 32718).

Physical Therapies for Psychosomatic Symptoms and Quality of Life Induced by Aromatase Inhibitors in Breast Cancer Patients: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the effects of Physical Therapies (PTs) on improvement in psychosomatic symptoms and quality of life (QOL) in breast cancer patients. DATA SOURCES: Seven databases (MEDLINE, EMBASE, Cochrane CENTRAL, China National Knowledge Infrastructure, Wangfang, VIP, and China Biology Medicine disc databases) were systematically searched from the database inception through May 18, 2021. STUDY SELECTION: Randomized controlled trials (RCTs) which compared acupuncture or exercise with a sham control or usual care for the treatment of aromatase inhibitors (AIs)-related psychosomatic symptoms and QOL. DATA EXTRACTION AND SYNTHESIS: Data were screened and extracted independently using predesigned forms. The quality of RCTs was assessed with the Cochrane Handbook for Systematic Reviews of Interventions. The effect size was calculated via random-effects modeling. The quality of evidence was evaluated with the Grading of Recommendations Assessment, Development and Evaluation approach. MAIN OUTCOMES AND MEASURES: The score of pain was measured with BPI scale and Western Ontario and the McMaster Universities Index (WOMAC) scale. Emotional state was measured with Pittsburgh Sleep Quality Index (PSQI), Hospital Anxiety and Depression Scale (HADS-A), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue). The QOL score was measured by self-reported measurements, including the Functional Assessment of Cancer Therapy-General (FACT-G) scale and 36-Item Short Form Survey (SF-36) scale. RESULTS: Eleven RCTs (with 830 patients) were included in the systematic review, and data from 10 RCTs (with 798 patients) were used in the meta-analysis. Results showed acupuncture significantly reduced worst pain scores (P < 0.00001, I 2 = 83.5%) [SMD = -0.81, 95% CI (-1.51, -0.11)], but the effect of exercise therapies was not significant in overall change in worst pain scores (P =0.006, I 2 = 72.3%) [SMD = -0.30, 95% CI (-0.76, 0.16)]. Both acupuncture and exercise resulted in little to no difference in overall change in HADS-A subscale (P = 0.026<0.05, I 2 = 79.8%) [WMD = -0.21, 95% CI (-3.44, 3.03)], PSQI subscale (P = 0.488, I 2 = 0%) [WMD = 0.98, 95% CI (-0.57, 2.53)], and FACIT-Fatigue subscale (P = 0.022<0.05, I 2 = 81.0%) [WMD = 1.6, 95% CI (-5.75, 8.94)]. Exercise (compared with usual care) was associated with improving overall change in health-related QOL (subscales of SF-36 tool) (P = 0, I 2 = 72.1%) [WMD = 7.97, 95% CI (5.68, 10.25)] and cancer-specific QOL (subscales of FACT-G tool) (P = 0.304, I 2 = 16%) [WMD = 1.16, 95% CI (0.34, 1.97)]. CONCLUSIONS AND RELEVANCE: This systematic review and meta-analysis suggested that based on moderate-level evidence, acupuncture was associated with significant reductions in pain intensity, and exercise might improve QOL in breast cancer patients treated with AIs. However, in psychosomatic symptoms such as anxiety, sleep disturbance, and fatigue, acupuncture and exercise training did not result in significant improvements.

Interventions for preventing influenza: An overview of Cochrane systematic reviews and a Bayesian network meta-analysis.

BACKGROUND: Influenza places a heavy public health burden in numerous countries every year. In addition to vaccines, there are some interventions that are effective in preventing influenza. OBJECTIVE: This overview of systematic reviews (SRs) aimed to evaluate the efficacy and safety of interventions for influenza prevention. SEARCH STRATEGY: We searched the Cochrane Database of Systematic Reviews, 2020, Issue 1 for relevant Cochrane SRs using the keywords "common cold," "influenza," and "flu." INCLUSION CRITERIA: Cochrane SRs that investigated the prevention of influenza were included. Participants included the general population without influenza or influenza-like symptoms, who were treated with preventative interventions and compared to individuals receiving no treatment or placebo. DATA EXTRACTION AND ANALYSIS: Two reviewers independently screened citations against pre-defined inclusion criteria and extracted data. The methodological quality of these SRs was evaluated using the Assessing the Methodological Quality of Systematic Reviews-II (AMSTAR-II) guidelines. The primary outcome of our analysis was the incidence of influenza, and the secondary outcomes were the incidence of influenza-like illness and hospitalization. In addition to the narrative summary of SR findings, we also pooled data from homogeneous trials among these SRs and produced evidence mapping. We conducted a network meta-analysis to compare the effect across interventions and used the Cochrane approach to grading of recommendations, assessment, development, and evaluation (GRADE) to assess the quality of evidence. RESULTS: Eleven Cochrane SRs were included, covering five medications, eleven vaccinations and four complementary therapies. Among these SRs, 73% scored "high" quality on AMSTAR-II rating. We found that eight interventions, including amantadine, garlic, and six different vaccines, were beneficial for reducing the incidence of influenza compared to placebo, while oseltamivir, zanamivir, Ganmao capsule, Echinacea, and another three types of vaccine were probably beneficial. Ganmao capsule ranked highest for influenza prevention in the network meta-analysis, followed by amantadine, garlic, and vaccines of all types. Monovalent inactivated parenteral vaccine was found to be beneficial in reducing the incidence of influenza-like illness. None of the interventions reduced the hospitalization rate. CONCLUSION: High-quality evidence showed that garlic or vaccine had advantages in preventing influenza, and that vitamin C is not effective. The effect of other interventions needs to be further verified with high-quality evidence.

Comparison between Xingnaojing Injection () and Naloxone in Treatment of Acute Alcohol Intoxication: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: To investigate the effectiveness and safety of Xingnaojing Injection (XNJ, ) compared with naloxone for the treatment of acute alcohol intoxication (AAI), and provide the latest evidence through evidence-based approach. METHODS: Seven electro-databases including PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure Databases, Chinese Biomedical Literature Database, Chinese Science and Technology Periodical Database (VIP) and Wanfang Database were searched from the inception to January 2018. Randomized controlled trials (RCTs) comparing XNJ with naloxone for patients with AAI and reporting at least one of the below outcomes were included: patients' conscious recovery time, stay length in emergency department, disappearance time of the ataxia symptom, the severity of the symptoms, the blood alcohol content as well as the adverse events. Methodological quality of included trials was assessed using the risk of bias tool which recommended by the Cochrane Collaboration. Meta-analysis was conducted by Review Manager 5.3 software. RESULTS: Totally 141 trials with 13,901 patients were included in this review, all of them were assessed as unclear or high risk of bias. Results showed that on the basis of routine therapy, standard dose XNJ (10-20 mL) may have similar results with naloxone on the recovery time of consciousness (MD 12 min, 95% CI 7.2-17.4 min) and disappearance time of symptoms (MD 6 min, 95% CI-13.8-25.8 min) for patients with AAI. Larger dose of XNJ Injection (21-40 mL) may speed up the time (almost 1 h earlier). Combination of XNJ and naloxone seemed superior to the naloxone alone for all the relevant outcomes. The average difference of time in consciousness recovery was 2 h and the number of AAI patients whose consciousness recovery within 1 h was above 50% the combination group than in the control group (RR 1.42, 95% CI 1.29 to 1.56). No severe adverse events or adverse reactions of XNJ were reported in the included trials. CONCLUSIONS: Low quality of evidence showed XNJ may have equal effect as naloxone and may achieve better effect as add-on intervention with naloxone for patients with AAI. We failed to evaluate the safety of XNJ Injection due to the insufficient evidence in this review. Registration number. in PROSPERO (No. CRD42018087804).

[Effect of protease in the lumen of rat intestine on inflammatory reaction during hemorrhagic shock].

OBJECTIVE: To investigate the effect of intraluminal administration of ulinastatin (a protease inhibitor) in the intestine on intestinal inflammation in rats with hemorrhagic shock. METHODS: Twenty-eight Wistar rats were randomized into control group (A), intestinal saline perfusion group (B), ulinastatin intestinal perfusion group (C), and intravenous ulinastatin injection group (D) (n=7). The mean arterial blood pressure (MAP) and survival time of the rats were recorded. The changes in human polymorphonuclear cell (PMN) CD11b expression were detected by flow cytometry. The leukocyte count was recorded at different time points after the treatment, and the pathology of the intestinal mucosa was observed comparatively. RESULTS: Groups C and D showed significantly slower reduction of the MAP than groups A and B after hemorrhagic shock (P<0.05). The survival time of the rats was the longest in group C (P<0.05). CD11b expression increased gradually during hemorrhagic shock in all the groups, but the expression level was the lowest in group C (P<0.05). Hemorrhagic shock caused a reduction in leukocyte counts, which remained the highest in group C (P<0.05). Group C also showed the least intestinal pathology among the 4 groups. CONCLUSION: Intestinal perfusion of ulinastatin can lower the reduction rate of MAP, attenuate plasma activation and intestinal inflammation, and prolong the survival of rats with hemorrhagic shock. These results indicate an important role of protease in intestinal inflammation during hemorrhagic shock.

[Early goal-directed therapy lowers the incidence, severity and mortality of multiple organ dysfunction syndrome].

OBJECTIVE: To investigate the effect of early goal-directed therapy (EGDT) on the incidence, severity and mortality of multiple organ dysfunction syndrome (MODS). METHODS: A prospective, randomized controlled trial was performed involving 273 patients in the early stage of shock at risk of potential MODS development. The patients were randomly divided into EGDT group (including 139 patients managed with EGDT) and control group (including 134 patients with conventional empirical therapy). The scores of APACHE II, blood lactate concentration (Lactate(0)) and SOFA scores (SOFA(0)) of the two groups were recorded on admission, and the lactate concentration on the second and fourth day of hospitalization (Lactate(2) and Lactate(4)), and the highest SOFA scores (SOFAT) after admission were also recorded. The discrepancy between the two SOFA scores (SOFA(S)), number of the dysfunctional organ, and the mortality in ICU of the two groups were calculated at the end of the study. RESULTS: The incidence of MODS in the EGDT group was significantly lower than that in control group (P=0.002). The Lactate(2), Lactate(4), SOFA(T), SOFA(S), and the number of dysfunctional organs in EGDT group were also significantly lower (P=0.045, 0.016, 0.009, 0.010, 0.002). EGDT was associated with a significantly lower total mortality rate of MODS than the conventional therapy (P=0.007), and also with a significantly lower mortality rate of MODS after controlling for severe sepsis (P=0.047 and 0.044). CONCLUSION: EGDT can decrease the incidence and severity of MODS, and can effectively decrease the mortality of MODS irrespective of the presence of severe sepsis.