Network meta-analysis on efficacy and safety of different biologics for ulcerative colitis.

BACKGROUND: Therapeutic options for ulcerative colitis (UC) have increased since the introduction of biologics a few decades ago. Due to the wide range of biologics available, physicians have difficulty in selecting biologics and do not know how to balance the best drug between clinical efficacy and safety. This study aimed to compare the efficacy and safety of biologics in treating ulcerative colitis. METHODS: In this study, eight electronic databases (PubMed, Web of Science, Cochrane, Embase, Sinomed, China National Knowledge Infrastructure, Chongqing VIP Information, and WanFang Data) were searched to collect eligible studies without language restrictions. Retrieved 1 June 2023, from inception. All articles included in the mesh analysis are randomised controlled trials (RCTs). The inclusion of drugs for each outcome was ranked using a curved surface under cumulative ranking (SUCRA). Higher SUCRA scores were associated with better outcomes, whereas lower SUCRA scores were associated with better safety. This study has registered with PROSPERO, CRD42023389483. RESULTS: Induction Therapy: Among the biologic therapies evaluated for induction therapy, vedolizumab demonstrated the highest efficacy in achieving clinical remission (OR vs daclizumab, 9.09; 95% CI, 1.01-81.61; SUCRA 94.1) and clinical response. Guselkumab showed the lowest risk of recurrence of UC (SUCRA 94.9%), adverse events resulting in treatment discontinuation (SUCRA 94.8%), and serious infections (SUCRA 78.0%). Maintenance Therapy: For maintenance therapy, vedolizumab ranked highest in maintaining clinical remission (OR vs mesalazine 4.36; 95% CI, 1.65-11.49; SUCRA 89.7) and endoscopic improvement (SUCRA 92.6). Infliximab demonstrated the highest efficacy in endoscopic improvement (SUCRA 92.6%). Ustekinumab had the lowest risk of infections (SUCRA 92.9%), serious adverse events (SUCRA 91.3%), and serious infections (SUCRA 67.6%). CONCLUSION: Our network meta-analysis suggests that vedolizumab is the most effective biologic therapy for inducing and maintaining clinical remission in UC patients. Guselkumab shows promise in reducing the risk of recurrence and adverse events during induction therapy. Infliximab is effective in improving endoscopic outcomes during maintenance therapy. Ustekinumab appears to have a favorable safety profile. These findings provide valuable insights for clinicians in selecting the most appropriate biologic therapy for UC patients.

[Placebo control and its methodological issues on clinical trials of acupuncture therapy].

The paper introduces the placebo acupuncture simulation devices commonly used in clinical trial of acupuncture therapy. These devices are composed of Streitberger, Park, Takakura, Foam and Phantom acupuncture. Because acupuncture therapy is a kind of complex intervention, there are the controversies in methodology for the acupuncture placebo control of clinical trial. Placebo acupuncture may be an effective control, with a certain of specific therapeutic effect. The blinding effect of placebo acupuncture is highly questioned, specially, the sensation of deqi is hardly imitated during acupuncture. On these grounds, in this research, the suggestions has been proposed on the selection and the setting of placebo control in clinical trial of acupuncture therapy.

Excessive Treadmill Training Produces different Cardiac-related MicroRNA Profiles in the Left and Right Ventricles in Mice.

High-volume training followed by inadequate recovery may cause overtraining. This process may undermine the protective effect of regular exercise on the cardiovascular system and may increase the risk of pathological cardiac remodelling. We evaluated whether chronic overtraining changes cardiac-related microRNA profiles in the left and right ventricles. C57BL/6 mice were divided into the control, normal training, and overtrained by running without inclination, uphill running or downhill running groups. After an 8-week treadmill training protocol, the incremental load test and training volume results showed that the model had been successfully established. The qRT-PCR results showed increased cardiac miR-1, miR-133a, miR-133b, miR-206, miR-208b and miR-499 levels in the left ventricle of the downhill running group compared with the left ventricle of the control group. Similarly, compared with the control group, the downhill running induced increased expression of miR-21, miR-17-3p, and miR-29b in the left ventricle. Unlike the changes in the left ventricle, no difference in the expression of the tested miRNAs was observed in the right ventricle. Briefly, our results indicated that overtraining generally affects key miRNAs in the left ventricle (rather than the right ventricle) and that changes in individual miRNAs may cause either adaptive or maladaptive remodelling with overtraining.

Regulation of Circulatory Muscle-specific MicroRNA during 8 km Run.

Acute prolonged endurance running has been shown to alter muscle-specific circulating microRNA (miRNA) levels. Here, eighteen participants completed an 8 km run. We assessed the levels of hsa-miR-1-3p, -133a-3p, -133b, and -206 and their correlation with conventional biomarkers following exercise. Compared to before exercise (Pre), 8 km run significantly increased the lactate level immediately after exercise (0 h). Myoglobin (Mb) level increased at 0 h while creatine kinase (CK) level increased 24 h after exercise (24 h). The levels of creatine kinase MB isoenzyme (CK-MB) and cardiac troponin I (cTnI) were all elevated at 24 h and within the normal physiological range; The levels of hsa-miR-1-3p, -133a-3p, -133b significantly increased at 0 h but only hsa-miR-133a-3p still elevated at 24 h. Only hsa-miR-206 level decreased at 24 h; Additionally, the changes of hsa-miR-1-3p and hsa-miR-133a-3p were correlated with Mb at 24 h. These findings suggest that muscle-specific miRNA elevation in plasma is likely physiological and that these miRNA may be used as potential biomarkers for load monitoring in individuals.

Excessive Treadmill Training Enhances Brain-Specific MicroRNA-34a in the Mouse Hippocampus.

Background: An imbalance between total training load and total recovery may cause overtraining (OT). The purpose of the present study was to verify the effects of OT on the expression of brain-derived neurotrophic factor (BDNF), its receptor tropomyosin receptor kinase B (TrkB) and p75 and the dynamic expression patterns of brain-specific miR-34a and miR-124 or inflammation-related miR-21 and miR-132 in the mouse hippocampus. Method: Eight weeks old C57BL/6J mice were randomly assigned to the control (CON), normal training (NT) and OT groups. An 8-week OT training protocol was applied to evaluate the phenotype of mice endurance (incremental load test, ILT) and cognitive capacity (Morris water maze test). We used qRT-PCR and immunoblotting to detect changes in the molecular level of hippocampal samples. Result: Compared with the CON, both NT and OT decreased bodyweight after 8-week training. After 8-week of training, NT increased the exhaustion velocity (EV) while the EV of OT was lower than NT. Mice in NT decreased the escape latency than CON. The percentage of time spent in the probe quadrant and the number of crossing platform times in NT were higher than CON and OT. The BDNF, p75 and TrkB mRNA levels were increased in NT than CON, only the p75 mRNA was increased in OT. The NT exhibited increased protein levels of BDNF and TrkB compared to CON. The protein expression of BDNF was decreased in OT than NT and CON. The protein level of p75 in the OT was higher than in NT and CON. In addition, the phosphorylation level of TrkB in OT was higher than CON and NT. Only the miR-34a level was increased in the OT. Moreover, the expression of miR-34a was found to be negatively correlated with the expression of BDNF, and the increase in miR-34a level was accompanied by a decrease in performance. Conclusion: In summary, the training-evoked increase in the BDNF level may help to improve performance, whereas this conditioning is lost after OT. Moreover, miR-34a potentially mediated changes in the expression of BDNF and may reflect the decrease in performance after OT.

Time-Course Responses of Muscle-Specific MicroRNAs Following Acute Uphill or Downhill Exercise in Sprague-Dawley Rats.

Objective: The physiological characteristics and acute responses underpinning uphill running differ from those of downhill running and remain less understood. This study aimed to evaluate time-course changes of muscle-specific microRNA (miRNA) responses in striated muscle or circulation in response to uphill and downhill running. Methods: Male Sprague-Dawley rats (n = 84) were randomly assigned to a sedentary group (n = 12) and an exercise group (n = 72). The exercise group performed 90 min of uphill or downhill running. The striated muscle (quadriceps, gastrocnemius, soleus, and cardiac muscle) or circulation (plasma, exosome, exosome-free) levels of six muscle-specific miRNAs (miR-1, miR-133a, miR-133b, miR-206, miR-208a, and miR-499) were assessed at rest, immediately following exercise, and during recovery (1 h and 48 h). Results: Our results show that miR-1 and miR-133a levels are both decreased in quadriceps following downhill running (p < 0.05) while there is no change after uphill running (p > 0.05). In gastrocnemius, both uphill and downhill running decreased miR-1 level immediately after exercise and returned to baseline during recovery (p < 0.05): interestingly, only miR-499 significantly increased following uphill running (p > 0.05). Of the cell-free miRNAs in circulation, only the miR-133b levels in plasma were not affected following uphill running (p > 0.05); the other miRNA levels significantly increased immediately after exercise (p < 0.05), decreased at 1 h and significantly increased at 48 h after exercise (p < 0.05). All selected miRNA levels in exosomes were not affected following uphill running (p > 0.05), while all selected miRNA levels significantly increased during early recovery after downhill running (p > 0.05). In addition, only the miR-133a level in the exosome-free condition showed significant changes following uphill running (p < 0.05), while miR-1, miR-133a, and miR-499 levels showed significant changes after downhill running (p < 0.05). Conclusion: The results indicate that miRNA undergoes dynamic changes in tissue may play an important role in regulating different stress/adaptation following uphill and downhill running. It is likely that changed miRNA levels in plasma may act as a new biomarker for monitoring whole muscular stress during recovery.

[Effects of sustained military physical related activity on balance ability].

OBJECTIVE: To evaluate the effects of sustained military physical related activity on balance abilities and the role of visual system in it, so as to provide the basis for precise training. METHODS: Fifty-four healthy males (age: 20.28±3.72 y, height: 173.21±5.67 cm; weight: 64.29±5.12 kg) were recruited in this experiment. Multiple military subjects were completed within 36 hours, and the workload was recorded (randomly select 11 people). After military activity, the balance abilities with opened eyes (54 people) and closed eyes (randomly selected 27 people) were evaluated. RESULTS: In terms of internal load, the heart rates (HR), excess post-exercise oxygen consumption (EPOC) and training impulse (TRIMP) for all exercises were increased significantly in military activity compared with rest (P＜0.05). Regard to balance abilities, compared to the rest with eyes-opened, the sway path-total (SPT), sway path-A-P ( SPAP ), sway path-M-L (SPML), sway V-total (SVT), sway V-A-P (SVAP), and sway V-M-L (SVML)after sustained military activity with eyes-opened were increased significantly (P＜0.05), while sway maximal amplitude-A-P (SMAAP), sway maximal amplitude-M-L (SMAML), and area of 100% ellipse (AE) had no significant changes; Compared to the rest, all indicators after the military activity with eyes-closed were significantly increased (P＜0.05). So vision could control the amplitude and area after the military activity. CONCLUSION: Sustained military related activity can damage the balance ability. After sustained military activity, the degree of damage of the balance ability in the closed-eyes is greater than that of the open-eyes, the amplitude and range of the center of gravity are increased, indicates that the visual system plays major role in controlling attitude stability.

[Effect of lower-limb dominance and non-dominance shuttle runs under load carriage on the balance responses in young cadets].

OBJECTIVE: This test was designed to evaluate the effect of lower-limb dominance and non-dominance shuttle runs under load carriage during different exercise load at the same exercise intensity on the balance responses. METHODS: Ten healthy young males were joined in this experiment, they were (20.80±2.04) years old and (173.99±2.87) cm tall. In a randomized cross-over design, they performed four times shuttle runs under unilateral load carriage:20 m×5 at dominant side, 20 m×5 at non-dominant side, 20 m×10 at dominant side, 20 m×10 at non-dominant side respectively. Balance abilities were evaluated immediately and 20 minute post-exercise respectively, and R-R interval was recorded. RESULTS: The HR, EPOC and TRIMP for all exercise load were increased significantly after shuttle runs compared to rest (P<0.01), the EPOC and TRIMP for 20 m×10 shuttle runs were significantly higher than those for 20 m×5 shuttle runs at the dominant and non-dominant side (P<0.01). Compared to the rest, the instability indices (general, anteroposterior and mediolateral movement) for 20 m×5 and 20 m×10 shuttle runs immediately post-exercise at the dominant and non-dominant side were increased significantly (P<0.05), and the magnitude of the mediolateral movement for 20 m×10 shuttle runs was higher than that of 20 m×5 shuttle runs (P<0.05). While there were no obvious difference between the dominant and the non-dominant side (P>0.05), which showed symmetrical change. In addition, during 20 minute recovery, the balance ability for all exercise load was returned to the rest value (P>0.05). CONCLUSIONS: The shuttle runs could impair the trunk control ability immediately post-exercise, the magnitude of mediolateral movement was increased as the exercise load increased. The changes of balance responses were similar between the dominant and the non-dominant side, the dominant and the non-dominant side might show cross-effects.

Incidence and Characteristics of Meniscal Injuries in Cadets at a Military School, 2013-2015.

CONTEXT: Meniscal injury is common among military service members. OBJECTIVE: To examine the incidence and characteristics of meniscal injuries in cadets at a single military institution between 2013 and 2015. DESIGN: Cohort study. SETTING: Meniscal-injury data were collected at the Center of Rehabilitation Training, the People's Liberation Army University of Science and Technology. PATIENTS OR OTHER PARTICIPANTS: A total of 2479 cadets participating in physical activities between 2013 and 2015. MAIN OUTCOME MEASURE(S): Injury rates, injury proportions by body mass index, risk ratios (RRs), and injury proportion ratios were reported with 95% confidence intervals (CIs). RESULTS: The overall incidence rate was 10.08 (95% CI = 6.84, 14.84) per 1000 person-years. A multiple-comparisons test revealed differences in the relative injury rate in overweight or obese cadets versus normal-weight cadets and underweight cadets (χ2 = 8.98, P = .01). No differences were found between injured normal-weight cadets and underweight cadets (P = .66, RR = 1.39, 95% CI = 0.32, 6.06) or between injured overweight or obese cadets and injured underweight cadets (P = .24, RR = 0.42, 95% CI = 0.09, 1.91). The absolute injury rate was higher for overweight and obese cadets compared with normal-weight cadets (P < .01, RR = 0.30, 95% CI = 0.13, 0.69). The overall proportional distribution for patterns of injury was 2:1 (medial to lateral) for meniscal injuries. Grade 2 injuries were the most common. CONCLUSIONS: The high frequency and level of severity of meniscal injuries may negatively affect the readiness and health of cadets. High body mass index was a risk factor for meniscal injury.

Acute responses of circulating microRNAs to low-volume sprint interval cycling.

Low-volume high-intensity interval training is an efficient and practical method of inducing physiological responses in various tissues to develop physical fitness and may also change the expression of circulating microRNAs (miRNAs). The purpose of the present study was to examine whether miRNAs for muscle, heart, somatic tissue and metabolism were affected by 30-s intervals of intensive sprint cycling. We also examined the relationship of these miRNAs to conventional biochemical and performance indices. Eighteen healthy young males performed sprint interval cycling. Circulating miRNAs in plasma were detected using TaqMan-based quantitative PCR and normalized to Let-7d/g/i. In addition, we determined the levels of insulin-like growth factor-I, testosterone and cortisol, and anaerobic capacity. Compared to plasma levels before exercise muscle-specific miR-1 (0.12 ± 0.02 vs. 0.09 ± 0.02), miR-133a (0.46 ± 0.10 vs. 0.31 ± 0.06), and miR-133b (0.19 ± 0.02 vs. 0.10 ± 0.01) decreased (all P < 0.05), while miR-206 and miR-499 remained unchanged. The levels of metabolism related miR-122 (0.62 ± 0.07 vs. 0.34 ± 0.03) and somatic tissues related miR-16 (1.74 ± 0.27 vs. 0.94 ± 0.12) also decreased (both P < 0.05). The post-exercise IGF-1 and cortisol concentrations were significantly increased, while testosterone concentrations did not. Plasma levels of miR-133b correlated to peak power (r = 0.712, P = 0.001) and miR-122 correlated to peak power ratio (r = 0.665, P = 0.003). In conclusion sprint exercise provokes genetic changes for RNA related to specific muscle or metabolism related miRNAs suggesting that miR-133b and miR-122 may be potential useful biomarkers for actual physiological strain or anaerobic capacity. Together, our findings on the circulating miRNAs may provide new insight into the physiological responses that are being performed during exercise and delineate mechanisms by which exercise confers distinct phenotypes and improves performance.

[Effect of jianpi tongluo jiedu recipe on expression levels of COX-2, NF-kappaBp65, and Bcl-2 in gastric mucosa of patients with precancerous lesions of gastric cancer].

OBJECTIVE: To explore the effect of Jianpi Tongluo Jiedu Recipe (JTJR) on protein expression levels of COX-2, NF-kappaBp65, Bcl-2, and Bax, mRNA expression levels of COX-2 and Bcl-2, and the apoptotic index (Al) in gastric mucosa of patients with precancerous lesions of gastric cancer (PL-GC). METHODS: Totally 65 PLGC patients were recruited and treated by JTJR (modified by syndrome typing), one dose per day for six successive months. Protein expression levels of COX-2, NF-KBp65, Bcl-2, and Bax were detected in 65 patients using immunohistochemical (IHC) assay before and after treatment. mRNA expression levels of COX-2 and Bcl-2 were detected in 54 patients using reverse transcription-polymerase chain reaction (RT-PCR). Meanwhile, changes of Al was detected in 65 patients using TdT-mediated dUTP-biotin nick end labeling (TUNEL) fluorescence method. RESULTS: After treatment with JTJR, positive protein expression levels of COX-2, NF-KBp65, and Bcl-2 were obviously decreased in the gastric mucosa of PLGC patients (P <0.01), but Bax positive protein expression was found to be higher (P < 0.05). At the same time mRNA expression levels of COX-2 and Bcl-2 were significantly lower after treatment than before treatment (P < 0.05, P < 0.01); Al also increased after treatment (P < 0.05). CONCLUSION: JTJR could promote apoptosis possibly via NF-kappaBp65/COX-2, COX-2/Bcl-2, and NF-kappaBp65/Bcl-2 signaling pathways, thereby affecting PLGC patients.

[Proteomic analysis of myocardial hypertrophy induced by left kidney artery coarctation in rats].

AIM: To identify the expression of proteins in cardiomyocytes in rats with left kidney artery coarctation. METHODS: 16 male SD rats were separated into 2 groups (n=8): 2 kidney 1 Clip group (2K1C) and sham operation group (SO). The postoperational 8th week, after examination by normal doppler and tissue doppler echocardiography, the extracted proteins from cardiomyocytes were isolated by two-dimensional gel electrophoresis with staining. The gel images were acquired by scanner and 2-DE analysis software. Different spots observed on two 2D gels were selected and identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). RESULTS: Overall, 21 protein spots showed significant difference, and 14 out of which were identified. CONCLUSION: Kidney artery coactation-induced cardiac hypertrophy displays different expression of proteins in cardiomyocytes.

Swimming training can affect intrinsic calcium current characteristics in rat myocardium.

Endurance exercise is widely assumed to improve cardiac function in humans, but the mechanisms involved in such changes are not clearly understood. The purpose of this study is to determine whether training elicits adaptations at the level of the L-type Ca(2+) channel. Sprague-Dawley rats performed swimming training at either moderate intensity (MOD) or high intensity (HIGH) during 8 weeks. The trained rats were studied by echocardiography and the whole-cell L-type Ca(2+) currents (I (Ca,L)) characteristics in a single cell were measured by standard whole-cell patch-clamp recording technique. Echocardiography showed that septal and posterior wall thickness in MOD and HIGH increased with the increased LV mass by 43 and 41%, respectively (P < 0.05). Training (P < 0.05) increased mean myocyte capacitance (approximately 38% in MOD and HIGH) and myocyte length (approximately 20% longer in MOD and 26% longer in HIGH), thus providing electrophysiological and morphological evidence that the training elicited LV cardiocyte hypertrophy. Mean peak I (Ca,L) was not different in three groups. However, whole-cell I (Ca,L) density was decreased in MOD and HIGH versus sedentary (P < 0.05), but there was no significant difference between MOD and HIGH. The present study provides the evidence of a training adaptation in intrinsic I (Ca,L) characteristics in ventricular myocardium, which demonstrates a remarkable adaptive plasticity of L-type channel characteristics in training rat heart.

Proteomic adaptation to chronic high intensity swimming training in the rat heart.

Cardiac hypertrophy induced by exercise is associated with less cardiac fibrosis and better systolic and diastolic function, suggesting that the adaptive mechanisms may exist in exercise-induced hypertrophy. To identify molecular mechanisms by which exercise training stimulates this favorable phenotype, a proteomic approach was employed to detect rat cardiac proteins that were differentially expressed or modified after exercise training. Sixteen male Sprague-Dawley rats were divided into trained (T) and control(C). T rats underwent eight weeks of swimming training seven days/week, using a high intensity protocol. Hearts were used to generate 2-D electrophoretic proteome maps. Training significantly altered 23 protein spot intensities (P<0.05), including proteins associated with the mitochondria oxidative metabolism, such as prohibitin, malate dehydrogenase, short-chain acyl-CoA dehydrogenase, triosephosphate isomerase, electron transfer flavoprotein subunit beta, ndufa10 protein, ATP synthase subunit alpha and isocitrate dehydrogenase [NAD] subunit. Additionally, Prohibitin was increased in the exercise-induced hearts. Cytoskeletal, signal pathway, stress and oxidative proteins also increased within T groups. These results strongly support the notion that the observed changes in the expression of energy metabolism proteins resulted in a potential increase in the capacity to synthesise ATP, probably via mitochondrial oxidative metabolism. The observed changes in the expression of these metabolic and structural proteins induced by training may beneficially influence heart metabolism, stress response and signalling paths, and therefore improve the overall cardiac function.

The upper limit of physiological cardiac hypertrophy in elite male and female athletes in China.

Physiological hypertrophy in response to physical training is important in the differentiation of physiological and pathological left ventricular hypertrophy. The goal of our study was to define the structural characteristics of the heart in Chinese athletes. Between June 2005 and August 2005, 339 (165 male, 174 female) elite Chinese athletes from 19 sports were profiled. Standard two-dimensional guided M-mode and Doppler echocardiography were employed to evaluate left ventricular morphology and function. Of the 165 male athletes, 19 (11.5%) male athletes presented with an LVIDd>or=60 mm, with an upper limit of 65 mm. Only three male athletes presented with wall thickness values>or=13 mm. Eighteen (10.3%) female athletes presented with an LVIDd>or=50 mm, and seven (4.2%) female athletes presented with an LVIDd>or=55 mm, with an upper limit of 62 mm. None were found to have a maximum wall thickness greater than 11 mm. Systolic and diastolic functions were within normal limits for all athletes. Results from the present study suggest that upper normal limits for left ventricular wall thickness and LVIDd are 14 and 65 mm for elite male Chinese athletes, and 11 mm and 62 mm for elite female Chinese athletes. Values in excess of these should be viewed with caution and should prompt further investigation to identify the underlying mechanism for the observed left ventricular hypertrophy.

Cardiovascular pre-participation screening of young competitive athletes for prevention of sudden death in China.

The cardiovascular pre-participation screening proposal for young competitive athletes has the potential to save young lives. This study aimed to identify individuals at risk for potentially lethal cardiovascular diseases in athletes before competition. Between June 2005 and July 2005, 351 (170 male and 181 female) elite Chinese athletes from 21 sports were profiled. The 12-lead electrocardiogram and echocardiography were employed to evaluate cardiovascular diseases. The vast majority had no definitive evidence of cardiovascular disease. However, abnormal ECGs were identified in 16 athletes (4.5%), including 4 with distinctly abnormal and 12 with mildly abnormal patterns. Only 13 athletes (3.7%) had echocardiographic evidence of relatively mild valve regurgitation that had not been previously suspected. In three athletes with relatively mild ventricular septal hypertrophy (13-14 mm), it was not possible to discern with absolute certainty whether the wall thickening was a manifestation of hypertrophic cardiomyopathy or secondary to athletic conditioning ("athlete heart"). This screening protocol identified no athletes with definite evidence of hypertrophic cardiomyopathy, Marfan's syndrome or other cardiovascular diseases that convey a significant potential risk for sudden death or disease progression during athletic activity. This is largely due to the relative low prevalence of conditions resulting in sudden cardiac death in young athletes and high false positive/negative rates in the tests used as part of the screening process (due to a large overlap between cardiovascular changes due to pathology and those due to intense training).