Random Number Research Articles

A High-Performance FPGA PRNG Based on Multiple Deep-Dynamic Transformations.

Pseudo-random number generators (PRNGs) are important cornerstones of many fields, such as statistical analysis and cryptography, and the need for PRNGs for information security (in fields such as blockchain, big data, and artificial intelligence) is becoming increasingly prominent, resulting in a steadily growing demand for high-speed, high-quality random number generators. To meet this demand, the multiple deep-dynamic transformation (MDDT) algorithm is innovatively developed. This algorithm is incorporated into the skewed tent map, endowing it with more complex dynamical properties. The improved one-dimensional discrete chaotic mapping method is effectively realized on a field-programmable gate array (FPGA), specifically the Xilinx xc7k325tffg900-2 model. The proposed pseudo-random number generator (PRNG) successfully passes all evaluations of the National Institute of Standards and Technology (NIST) SP800-22, diehard, and TestU01 test suites. Additional experimental results show that the PRNG, possessing high novelty performance, operates efficiently at a clock frequency of 150 MHz, achieving a maximum throughput of 14.4 Gbps. This performance not only surpasses that of most related studies but also makes it exceptionally suitable for embedded applications.

Loophole-Free Test of Local Realism via Hardy's Violation.

Bell's theorem states that the quantum mechanical description of physical quantities cannot be fully explained by local realistic theories, laying a solid basis for various quantum information applications. Hardy's paradox is celebrated as the simplest form of Bell's theorem concerning its "All versus Nothing" approach to test local realism. However, due to experimental imperfections, existing tests of Hardy's paradox require additional assumptions of the experimental systems, and these assumptions constitute potential loopholes for faithfully testing local realistic theories. Here, we experimentally demonstrate Hardy's nonlocality through a photonic entanglement source. By achieving a detection efficiency of 82.2%, a quantum state fidelity of 99.10%, and applying high-speed quantum random number generators for the measurement setting switching, the experiment is implemented in a loophole-free manner. During 6h of running, a strong violation of P_{Hardy}=4.646×10^{-4} up to 5 standard deviations is observed with 4.32×10^{9} trials. A null hypothesis test shows that the results can be explained by local realistic theories with an upper bound probability of 10^{-16348}. These testing results provide affirmative evidence against local realism, and establish an advancing benchmark for quantum information applications based on Hardy's paradox.

Enhanced recovery after surgery-based nursing in older patients with postoperative intestinal obstruction after gastric cancer surgery: A retrospective study.

Gastric cancer-related morbidity and mortality rates are high in China. Patients who have undergone gastric cancer surgery should receive six cycles of chemotherapy according to their condition. During this period, intestinal obstruction is likely to occur. Electrolyte balance disorders, peritonitis, intestinal necrosis, and even hypovolemic shock and septic shock can seriously affect the physical and mental recovery of patients and threaten their health and quality of life (QoL). To quantitatively explore the effects of enhanced recovery after surgery (ERAS)-based nursing on anxiety, depression, and QoL of elderly patients with postoperative intestinal obstruction after gastric cancer. The clinical data of 129 older patients with intestinal obstruction after gastric cancer surgery who were treated and cared for in our hospital between January 2019 and December 2021 were examined retrospectively. Nine patients dropped out because of transfer, relocation, or death. According to the order of admissions, the patients were categorized into either a comparison group or an observation group according to the random number table, with 60 cases in each group. After nursing care, the observation group required significantly less time to eat for the first time, recover bowel sounds, pass gas, and defecate than the comparison group (P < 0.05). No significant difference was noted in nutrition-related indicators between the two groups before care. Before care, the Symptom Check List-90 scores between the two groups were comparable, whereas anxiety, depression, paranoia, fear, hostility, obsession, somatization, interpersonal sensitivity, and psychotic scores were significantly lower in the observation group after care (P < 0.05). The QoL scores between the two groups before care did not differ significantly. After care, the physical, social, physiological, and emotional function scores; mental health score; vitality score; and general health score were significantly higher in the observation group, whereas the somatic pain score was significantly lower in the observation group (P < 0.05). ERAS-based nursing combined with conventional nursing interventions can effectively improve patient's QoL, negative emotions, and nutritional status; accelerate the time to first ventilation; and promote intestinal function recovery in elderly patients with postoperative intestinal obstruction after gastric cancer surgery.

Remote physical activity intervention to promote physical activity and health in adolescent girls (the HERizon project): a multi-arm, pilot randomised trial

BackgroundEngaging in physical activity (PA) during adolescence is beneficial for health and positive development. However, most adolescent girls have low PA levels, and there is a need for interventions outside of school hours. This pilot randomised controlled trial aimed to explore the preliminary effectiveness of three different remote PA interventions in increasing adolescent girls’ moderate-to- vigorous PA (MVPA), fitness and psychosocial outcomes.MethodsGirls living in the UK or Ireland, aged between 13 and 16 years old, who wished to increase their activity levels, were eligible for the study. Using a random number generator, participants (n = 153; 14.8y ± 1.4) were randomised into one of three 12-week intervention groups (i) PA programme, (ii) Behaviour change support, or (iii) Combined PA programme and Behaviour change support, or (iv) a Comparison group. Outcome measures included accelerometer and self-reported PA, physical fitness (cardiorespiratory fitness; 20 m shuttle run, muscular endurance; push up, muscular strength; long jump), and psychosocial assessments (perceived competence; body appreciation; self-esteem; behavioural regulation). Linear mixed models were used to analyse differences between each intervention arm and the comparison group immediately postintervention (12 weeks) and at follow up (3-months post-intervention), while adjusting for potential confounders.ResultsParticipation in the PA programme group was associated with higher perceived competence (0.6, 95% CI 0.1 to 1.2), identified regulation (0.7, 95% CI 0.2 to 1.1) and intrinsic motivation (0.9, 95% CI 0.2 to 1.6) at post-intervention. Participation in the Behaviour change group was associated with higher perceived competence at post-intervention (0.6, 95% CI 0.1 to 1.2), and higher push-up scores at the 3-month follow-up (4.0, 95% CI 0.0 to 7.0). Participation in the Combined group was also associated with higher perceived competence at post-intervention (0.8, 95% CI 0.2 to 1.4), and higher push-up scores at the 3-month follow-up (5.0, 95% CI 1.0 to 8.0). No other significant differences were found between the intervention arms and the comparison group.ConclusionResults suggest perceived competence increased across all intervention arms, while the PA programme group enhanced autonomous motivation in the short term. Intervention arms with behaviour change support appear most promising in improving muscular endurance. However, a larger scale trial is needed for a better understanding of between-group differences and the impact of intervention arms on MVPA and fitness, given the small sample size and short-term follow-up.

Memristive True Random Number Generator for Security Applications.

This study explores memristor-based true random number generators (TRNGs) through their evolution and optimization, stemming from the concept of memristors first introduced by Leon Chua in 1971 and realized in 2008. We will consider memristor TRNGs coming from various entropy sources for producing high-quality random numbers. However, we must take into account both their strengths and weaknesses. The comparison with CMOS-based TRNGs will serve as an illustration that memristor TRNGs stand out due to their simpler circuits and lower power consumption- thus leading us into a case study involving electroless YMnO3 (YMO) memristors as TRNG entropy sources that demonstrate good security properties by being able to produce unpredictable random numbers effectively. The end of our analysis sees us pinpointing challenges: post-processing algorithm optimization coupled with ensuring reliability over time for memristor-based TRNGs aimed at next-generation security applications.

One time pad for enhanced steganographic security using least significant bit with spiral pattern

Data is an important commodity in today’s digital era. Therefore, data needs to get adequate security to prevent misuse. A common data security practice in the transmission of information is cryptography. Another approach is steganography, which hides secret messages in other media that are not confidential and can be accessed by the public. In this study, the spiral pattern is used for data placement using the least significant bit (LSB) method. Modifications were made to the 2-bits LSB to increase the data capacity that can be hidden. In order to increase security, the data is first converted into a datastream using random numbers as one time pad (OTP). exclusive-OR (XOR) operation is performed on datastream and OTP to get encrypted data to be hidden. The results showed that the image quality of the steganography results at a capacity close to 100% was still fairly good, as indicated by a peak signal-to-noise ratio (PSNR) value greater than 46 dB. Visually, the steganographic image does not look different from the original one. Likewise, the use of random numbers as OTP succeeded in changing the hidden data significantly, as indicated by the avalanche effect value above 50%.

A demultiplexer-based dual-path switching true random number generator

This paper presents a demultiplexer (DEMUX) based dual-path switching true random number generator (TRNG). Unlike the classical single chain TRNG, the proposed TRNG utilizes DEMUXs to separate the cumulative jitter and occurrence of metastability in two paths. It also uses Ring Oscillator (RO) to increase the uncertainty of path switching time. Therefore, two sources of entropy are skilfully combined and no post-processing circuitry is required. The proposed structure is implemented on Xilinx Virtex-7 FPGA development board. The experimental results show that the proposed structure is able to achieve a high throughput of 500 Mbps with 33 Look-up Tables (LUTs) and 4 Flip-Flops (FFs). This effectively improves the throughput with high quality entropy and low hardware overhead.

Study on the effect and mechanism of Yanghe decoction Huacai on tissue repair ofsyndrome after anal fistula surgery.

To observe the clinical efficacy and safety of Yanghe decoction Huacai for the repair of Yin syndrome wounds with slow-healing after anal fistula surgery. A total of 120 patients with slow-healing negative wounds with after low-grade anal fistula surgery who met the inclusion criteria were divided into a treatment group and a control group based on a random number table method, with 60 patients in the treatment group and 60 patients in the control group. The treatment group was given Yanghe decoction Huacai in combination with routine treatment; the control group was only given routine treatment, in which the wound surface was disinfected with iodine, and then covered with sterile gauze. The course of treatment in both groups was 10 d. After treatment, the wound secretion score, wound granulation tissue score, the expression levels of basic fibroblast growth factor (bFGF), transforming growth factor β1 (TGF-β1), and epidermal growth factor (EGF) in the wound, wound healing time and clinical efficacy were compared. There was no significant difference in age or gender between the two groups (P > 0.05). On the 10th and 15th days after the surgery, the wound secretion scores were higher in the treatment group than in the control group (P < 0.01). Comparing the two groups at the 10th and 15th day after surgery, the granulation tissue growth scores in the treatment group were better than the in control group (P < 0.01). On the 10th and 15th day after operation, the expression levels of bFGF, TGF-β1 and EGF factors in the treatment group were stronger than those in the control group. The healing time of the wounds in the treatment group was significantly shorter than in the control group (P < 0.01). The clinical efficacy of the two groups after treatment was compared, and the overall efficacy of the treatment group was significantly higher than that of the control group (P < 0.01). Yanghe decoction Huacai have significant efficacy in the treatment of slow-healing wounds with Yin syndrome after anal fistula surgery. It improves wound secretions, promotes the growth of wound granulation tissue, and shortens wound healing time. Its mechanism of action may be related to the control of wound inflammation. It is related to increasing the expression of bFGF, TGF-β1 and EGF in wound tissue, and promoting wound angiogenesis and fibroblast proliferation.

Effects of Schisandrae Chinensis Fructus Lignans on Alertness of Rats With Sleep Deprived by Treadmill Exercise

Objective To investigate the effects of Schisandrae Chinensis Fructus lignans on the alertness of the rats with sleep deprived by treadmill exercise and the underlying neurobiological mechanism. Methods According to the random number table method,SD male rats were assigned into control,sleep deprivation,low-,medium-,and high-dose Schisandrae Chinensis Fructus lignans,and atomoxetine hydrochloride groups,with 8 rats in each group.The rats in other groups except the control group were subjected to sleep deprivation by treadmill exercise for 3 d.During the deprivation period,each administration group was administrated with the corresponding drug by gavage,and a 5-9 hole tester was used to test the alertness performance of rats in each group. Furthermore,other SD male rats were selected and randomized into control,sleep deprivation,Schisandrae Chinensis Fructus lignans (67.2 mg/kg) and atomoxetine hydrochloride groups,with 10 rats in each group.The rats were modeled with the sleep deprivation method the same as that above and administrated with corresponding agents.ELISA was employed to measure the serum level of orexin A in each group of rats.The protein levels of c-Fos,orexin receptor 1,and orexin receptor 2 in the prefrontal cortex of rats in each group were observed by immunofluorescence and Western blotting. Results Compared with the control group,sleep deprivation reduced the choice accuracy (P<0.001) and increased the omission responses,omission percent,and mean correct response latency (P=0.002,P=0.003,P=0.020).Compared with the sleep deprivation group,medium- and high-dose Schisandrae Chinensis Fructus lignans and atomoxetine hydrochloride improved the alertness of rats,as demonstrated by the increased choice accuracy (P=0.001,P=0.006,P<0.001) and reduced omission responses (P=0.001,P=0.001,P<0.001),omission percent (P=0.001,P=0.002,P<0.001),and mean correct response latency (P=0.018,P=0.003,P=0.014).Compared with the control group,the sleep deprivation group showed elevated level of orexin A in the serum (P<0.001),up-regulated expression of c-Fos (P<0.001),and down-regulated expression of orexin receptor 1 (P=0.037) in the prefrontal cortex.Compared with the sleep deprivation group,Schisandrae Chinensis Fructus lignans (67.2 mg/kg) and atomoxetine hydrochloride lowered the orexin A level in the serum (P=0.005,P=0.029),down-regulated the expression of c-Fos (P=0.028,P=0.036),and up-regulated the expression of orexin receptor 1 (P=0.043,P=0.013) in the prefrontal cortex. Conclusion Schisandrae Chinensis Fructus lignans may antagonize the alertness decrease caused by sleep deprivation by regulating the secretion of orexin and the expression of orexin receptor 1 in the prefrontal cortex.

Clinical effects of neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy on complications and recurrence in patients with advanced gastric cancer.

To compare the clinical effects of neoadjuvant chemoradiotherapy (NCRT) and neoadjuvant chemotherapy (NCT) on complications and recurrence in patients with advanced gastric cancer (AGC). This was a retrospective study. A total of 83 patients with AGC admitted to Chengde Central Hospital between Jan. 2019 and Jun. 2021 were selected and divided into the observation group(n=41) and the control group(n=42) using a random number table. Patients in the control group received XELOX chemotherapy, and those in the observation group received intensity-modulated radiotherapy (IMRT) with concurrent XELOX chemotherapy. Compared efficacy, pathological complete response rate (pCR), R0 resection rate, adverse reactions, and quality of life (QOL) before and after treatment between the two groups. The efficacy, pCR, and R0 resection rate of the observation group were significantly increased compared with those of the control group. Comparison of complications showed the number of patients experiencing gastrointestinal (GI) reactions, increased BUN, increased GPT, alopecia, and pigmentation in the observation group was decreased compared with that in the control group, with no statistically significant differences(p>0.05), and the number of patients experiencing myelosuppression was statistically significant between the two groups(p<0.05). There were no significant differences in sub-scores of physical, role, emotional, cognitive, and social functions and the overall score of QOL between the two groups(p>0.05) before treatment. NCRT is safer and more effective in patients with AGC compared with NCT, and can significantly improve the QOL of patients. It can be widely used in clinical practice.

Predicting effects of tunnel throttling of annular freeway vehicular flow by a continuum model

Fluid flow throttling is common in industrial and building services engineering. Similar tunnel throttling of vehicular flow is caused by the abrupt number reduction of roadway lane, as the tunnel has a lower lane number than in the roadway normal segment. To predict the effects of tunnel throttling of annular freeway vehicular flow, a three-lane continuum model is developed. Lane III of the tunnel is completely blocked due to the need of tunnel rehabilitation, etc. There exists mandatory net lane-changing rate from lane III to lane II just upstream of the tunnel entrance, which is described by a model of random number generated through a golden section analysis. The net-changing rate between adjacent lanes is modeled using a lane-changing time expressed explicitly in algebraic form. This paper assumes that the annular freeway has a total length of 100 km, a two-lane tunnel of length 2 km with a speed limit of 80 km/h. The free flow speeds on lanes I, II and III are assumed to be 110, 100 and 90 km/h respectively. Based on the three-lane continuum model, numerical simulations of vehicular flows on the annular freeway with such a tunnel are conducted with a reliable numerical method of 3rd-order accuracy. Numerical results reveal that the vehicular flow has a smaller threshold of traffic jam formation in comparison with the case without tunnel throttling. Vehicle fuel consumption can be estimated by interpolation with time averaged grid traffic speed and an assumed curve of vehicle performance. The vehicle fuel consumption is lane number dependent, distributes with initial density concavely, ranging from 5.56 to 8.00 L. Tunnel throttling leads to an earlier traffic jam formation in comparison with the case without tunnel throttling.

Clinical effect of hepatic artery interventional embolization and chemotherapy and its influence on P16 protein expression in patients with liver cancer.

To investigate clinical effects of hepatic artery interventional embolization chemotherapy (TACE) for primary hepatocellular carcinoma (PHC). 73 patients with PHC in our hospital from January 2017 to January 2018 were selected and divided into 37 cases in study group and 36 cases in control group by random number table method. The control group received only ultrasound-guided microwave ablation treatment, and the study group received TACE treatment again before surgery based on control group. The expression levels of cancer antigen 125 (CA125), alpha-fetoprotein (AFP), multiple tumor suppressors 1 (P16) proteins, and cancer antigen 19-9 (CA19-9) were compared between the two groups at different time periods after treatment, and the remission rate (ORR), control rate (DCR), complication rate at 3months after treatment and survival rate at 3years after treatment were compared. After 1year of treatment, ORR, DCR, and P16 protein levels in the study group were higher than those in the control group (P < 0.05), and differences were statistically significant; CA125, CA19-9, and AFP levels in study group were lower than those in the control group (P < 0.05), and differences were statistically significant. The regression equation showed that long-term survival rate of both groups showed decreasing trend over time, while long-term survival rate of study group was always higher than that of the control group. Comprehensive intervention for hepatic artery interventional chemoembolization in patients with primary hepatocellular carcinoma is more effective, which can effectively reduce incidence of complications and adverse effects in patients and help shorten treatment time of hepatic artery interventional chemoembolization in patients.

Asymptotics for ruin probabilities of a bidimensional risk model with a random number of delayed claims

This article considers a non-standard bidimensional risk model with constant force of interest, in which every main claim may cause a random number of delayed claims in an uncertain period of time. Specifically, if both the main claims and delayed claims are subexponential and follow some dependence structure, we drive precise asymptotic formulae for finite-time ruin probabilities, which generalize the results of Lu and Yuan (2022) and Li (2023b) to some extent.

Zhuyu Pills regulate p53/SLC7A11 signaling pathway-mediated oxidative damage and ferroptosis to treat atherosclerosis

This article aims to investigate the effect of Zhuyu Pills on atherosclerosis(AS) and decipher the underlying mechanism. The mouse model of AS was established by feeding with a high-fat diet for 12 weeks. The 50 successfully modeled mice with the apolipoprotein E knockout(ApoE~(-/-)) were assigned by the random number table method into 5 groups(n=10): model, low-, medium-, and high-dose(130.54, 261.08, 522.16 mg·kg~(-1), respectively) Zhuyu Pills, and atorvastatin calcium(10.40 mg·kg~(-1)). Ten C57BL/6J mice were selected as the blank group. The blank group and model group were administrated with an equal volume of normal saline, and other groups were administrated with corresponding drugs once a day for 12 weeks. At the end of drug intervention, hematoxylin-eosin(HE) staining was employed to observe the pathological changes of fat in the aorta, liver, and epididymis of mice, and the proportion of aortic plaque area, fat area in epididymis, and nonalcoholic fatty liver disease activity score(NAS) were calculated. Lipid and collagen deposition in the aorta was observed by oil red O staining and Masson staining, respectively, and the proportions of lipid and collagen deposition areas were calculated. The serum levels of superoxide dismutase(SOD), malondialdehyde(MDA), glutathione peroxidase(GSH-Px), and iron ion were measured by colorimetry. The expression of cyclooxygenase 2(COX2), ferritin heavy chain 1(FTH1), cystine/glutamate reverse transporter solute carrier family 7 member 11(SLC7A11), and glutathione peroxidase 4(GPX4) in the aorta was detected by the immunofluorescence assay. The level of tumor protein 53(p53) in the aorta was detected by immunohistochemistry. The protein levels of p53 and SLC7A11 in the aorta were determined by Western blot. The mRNA levels of p53, SLC7A11, GPX4, FTH1, prostaglandin G/H synthase 2(PTGS2), and reduced nicotinamide adenine dinucleotide phosphate oxidase 1(NOX1) in mouse aorta were determined by real-time PCR. The results showed that compared with the blank group, the model group showcased enlarged aortic plaque area, increased collagen fiber deposition, liver lipid deposition, and lipid droplets, and enlarged epididymal adipocytes. In addition, the modeling elevated the levels of iron ion and MDA and lowered the levels of SOD and GSH-Px in the serum, promoted the expression of p53 and COX2, down-regulated the protein and mRNA levels of FTH1, SLC7A11, and GPX4, and up-regulated the mRNA levels of PTGS2 and NOX1 in the aorta. Compared with the model group, low-, medium-, and high-dose Zhuyu Pills and atorvastatin calcium reduced the aortic plaque area, collagen deposition, liver lipid deposition, lipid droplets, and epididymal adipocyte volume, lowered the levels of iron ion and MDA and elevated the levels of SOD and GSH-Px in the serum, inhibited the expression of p53 and COX2, up-regulated the protein and mRNA levels of FTH1, SLC7A11, and GPX4, and down-regulated the mRNA levels of PTGS2 and NOX1 in the aorta. In conclusion, Zhuyu Pills exert definite therapeutic effect on aortic plaque in AS mice by regulating the p53/SLC7A11 signaling pathway to alleviate oxidative damage and inhibit ferroptosis.

Efficacy of a Combination of Functional Exercise and Psychological Interventions in Improving Postoperative Rehabilitation and Intervention Compliance in Patients With Breast Cancer

ObjectiveThis study aimed to investigate the effect of a combination of functional exercise and psychological interventions on postoperative rehabilitation and intervention compliance in patients with breast cancer (BC). MethodsThis study involved 100 patients with BC who underwent a radical mastectomy in our hospital between April 2020 and April 2021. We assigned patients to a control group (with a functional exercise intervention for patients) and an observation group (where patients received psychological interventions based on functional exercise) using a random number table. We observed and recorded the general data, intervention compliance, range of motion (ROM) of the shoulder joint pre and postintervention, pre and postintervention quality of life scores, and anxiety and depression scores before and after the interventions. ResultsThere were no significant differences in general data between the 2 groups (P > .05). Repeated measures analysis showed no preintervention differences in compliance, shoulder ROM, quality of life, or anxiety and depression scores (P > .05). Postintervention, compliance and shoulder ROM improved in both groups, with the observation group significantly outperforming the control group (P < .05). Quality of life scores improved significantly in both groups, with higher scores in the observation group at 1 and 3 months (P < .05). Anxiety and depression scores decreased in both groups, with the observation group showing lower scores than the control group (P < .05). ConclusionCombining functional exercise with psychological interventions improves treatment compliance, psychological status, postoperative shoulder ROM, and quality of life in breast cancer patients.

Efficacy and safety of Tongxin formula in the treatment of coronary microvascular disease: A randomized, double-blind, placebo-controlled clinical trial study

ObjectiveThe objective of this study was to evaluate the efficacy and safety of Tongxin Formula in the treatment of coronary microvascular disease. MethodsWe conducted a randomized, double-blind, placebo-controlled study simultaneously in two hospitals, consisting of 80 participants. Using a random number table, we assigned patients to the treatment and control groups. Patients in both groups received conventional Western medicine for coronary microvascular disease. In addition, those in the treatment group received Tongxin formula granules, while those in the control group received a placebo. The treatment course for both groups was three months, and the follow-up duration was six months. The primary efficacy indicators were coronary blood flow reserve and cardiovascular adverse events; the secondary efficacy indicators were the traditional Chinese medicine (TCM) syndrome score, the angina symptom score, the Seattle Angina Questionnaire (SAQ) score, left ventricular function, and adverse reactions. ResultsAfter treatment, patients in the treatment group showed significantly higher variation in the coronary flow reserve (CFR) levels (CFR >2) and improvement of diastolic function (peak filling rate, or PFR >2.5) than those in the control group (P < 0.05). After 6 months of follow-up, the incidence of cardiovascular events in the treatment group was significantly lower than that in the control group (P < 0.05). After 3 months of treatment and 6 months of follow-up, the total effective rates of TCM symptoms and angina symptoms, as well as the total SAQ standard scores, in the treatment group were higher than those in the control group (P < 0.05). There were no serious adverse reactions in either group before or after treatment, and there was no significant change (P > 0.05). ConclusionWe found that Tongxin Formula combined with conventional Western medicine can significantly improved the level of coronary blood flow reserve, reduced the occurrence of cardiovascular adverse events, improved the clinical symptoms of patients, and enhanced the quality of life of patients with coronary microvascular disease with favorable safety.

Two dose levels of once-weekly fosravuconazole versus daily itraconazole in combination with surgery in patients with eumycetoma in Sudan: a randomised, double-blind, phase 2, proof-of-concept superiority trial

Eumycetoma is an implantation mycosis characterised by a large subcutaneous mass in the extremities commonly caused by the fungus Madurella mycetomatis. Despite the long duration of treatment, commonly a minimum of 12 months, treatment failure is frequent and can lead to amputation. We aimed to compare the efficacy of two doses of fosravuconazole, a synthetic antifungal designed for use in onychomycosis and repurposed for mycetoma, with standard-of-care itraconazole, both in combination with surgery. This phase 2, randomised, double-blind, active-controlled, superiority trial was conducted in a single centre in Sudan. Patients with eumycetoma caused by M mycetomatis, who were aged 15 years or older, with a set lesion diameter (>2 cm and ≤16 cm) requiring surgery were included. There was a limit of 20 female patients in the initial enrolment, owing to preclinical toxicity concerns. Exclusion criteria included previous surgical or medical treatment for eumycetoma; presence of loco-regional lymphatic extension; osteomyelitis, or other bone involvement; pregnancy or lactation; severe concomitant diseases; a BMI under 16 kg/m2; contraindication to use of the study drugs; pre-existing liver disease; lymphatic extension; osteomyelitis; transaminase levels more than two times the laboratory's upper limit of normal, or elevated levels of alkaline phosphatase or bilirubin; or any history of hypersensitivity to any azole antifungal drug. Patients were randomly allocated in a 1:1:1 ratio to 300 mg fosravuconazole weekly for 12 months (group 1); 200 mg fosravuconazole weekly for 12 months (group 2); or 400 mg itraconazole daily for 12 months (group 3) using a random number list with non-disclosed fixed blocks of size 12, with equal allocation to each of the three arms within a block. To ensure masking between groups, placebo pills were used to disguise the difference in dosing schedules. All groups took pills twice daily with meals. In all groups, surgery was performed at 6 months. The primary outcome was complete cure at end of treatment at the month 12 visit, as evidenced by absence of mycetoma mass, sinuses, and discharge; normal ultrasonography or MRI examination of the eumycetoma site; and, if a mass was present, negative fungal culture from the former mycetoma site. The primary outcome was assessed in the modified intention-to-treat (mITT) population (all patients who received one or more treatment dose with one or more primary efficacy assessment). Safety was assessed in all patients who received one or more doses of the study drug. This study is registered with ClinicalTrials.gov (NCT03086226) and is complete. Between May 9, 2017, and June 10, 2021, 104 patients were randomly allocated (34 in group 1 and 2, respectively, and 36 in group 3). 86 (83%) of 104 patients were male and 18 (17%) patients were female. After an unplanned second interim analysis, the study was terminated early for futility. Complete cure at 12 months in the mITT population was 17 (50%) of 34 (95% CI 32-68) for group 1, 22 (65%) of 34 (47-80) for group 2, and 27 (75%) of 36 (58-88) in group 3. Neither dose of fosravuconazole was superior to itraconazole (p=0·35 for 200 mg fosravuconazole vs p=0·030 for 300 mg fosravuconazole). 83 patients had a total of 205 treatment-emergent adverse events, and two patients had serious adverse events that led to discontinuation, neither related to treatment. Treatment with either dose of fosravuconazole was not superior to itraconazole, and the two doses had a numerically lower efficacy. However, fosravuconazole presented no new safety signals, and its lower pill burden and reduced risk of drug-drug interactions compared with the relatively expensive and inaccessible itraconazole suggests further research into effective treatments with a shorter duration and higher cure rate, without the need for surgery are warranted. Drugs for Neglected Diseases initiative.

Effect of early pulmonary rehabilitation therapy on the pulmonary function of patients with stroke-associated pneumonia and analysis of its effectiveness.

This study aimed to evaluate the clinical effectiveness of early pulmonary rehabilitation (PR) treatment methods for stroke-associated pneumonia (SAP). This is a prospective, randomized controlled intervention study. Eighty SAP patients admitted to the rehabilitation department of Liuzhou People's Hospital from June 2020 to December 2021 were selected and divided into an intervention group (40 cases) and a control group (40 cases) using the random number table approach. Patients in both groups received conventional treatments. Patients in the intervention group received early PR interventions, while patients in the control group received conventional rehabilitation treatment. The clinical effectiveness and pulmonary function indexes were compared. The intervention group showed shorter durations of stay in the intensive care unit, relief from symptoms, and mechanical ventilation compared to the control group following treatment (P < 0.05). The total clinical efficacy after intervention in the treatment group was 82.50%, significantly higher than the control group's rate of 47.50% (P < 0.05). After 21 days of treatment, the forced expiratory volume in one second (FEV1)/predicted value in the intervention group was 64.92 ± 8.53, while it was 52.69 ± 7.08 in the other group. The FEV1/forced vital capacity in the intervention group was 59.73 ± 7.18, compared to 50.36 ± 6.54 in the control group. The intervention group had a clinical pulmonary infection score of 2.62 ± 1.13, while the control group had a score of 4.17 ± 2.08. The intervention group showed a significant improvement in lung function, with statistically significant differences compared to the other group (P < 0.05). Moreover, the intervention group had significantly lower levels of interleukin-4 and interleukin-10 compared to the control group, with statistical significance (P < 0.05). The average National Institute of Health Stroke Scale score of the intervention group was significantly lower than that of the control group in the second and third weeks after treatment (P < 0.05). Early comprehensive pulmonary rehabilitation can significantly enhance the pulmonary function and respiratory status of SAP patients and facilitate the early recovery of brain function. This approach archives significantly better outcomes compared to conventional PR; therefore, it is worth clinical implementation.

The clinical effectiveness of the Mind/Body Program for Infertility on wellbeing and assisted reproduction outcomes: a randomized controlled trial in search for active ingredients.

Does the Mind/Body Program for Infertility (MBPI) perform better, due to certain distinctive elements, than a partly matched support group in improving the wellbeing and medically assisted reproduction (MAR) outcomes of women with elevated distress levels in a clinical setting? While robust enhancements occurred in the wellbeing overall, the cognitive behavioural and formalized stress management elements of the MBPI allowed a significantly stronger improvement in trait anxiety, but not in other mental health and MAR outcomes, compared with a support group. Mind-body psychological programmes adjacent to MAR have been found to improve women's mental states and possibly increase chances of pregnancy. However, not enough is known about the programme's effectiveness among patients with elevated distress levels in routine clinical settings, nor is it clear which of its particular ingredients are specifically effective. A pre-post design, single-centre, randomized controlled trial was performed between December 2019 and October 2022 (start and end of recruitment, respectively). The sample size (n = 168) was calculated to detect superiority of the MBPI in improving fertility-related quality of life. Randomization was computer-based, with random numbers concealing identities of patients until after allocation. The trial was conducted at a large university teaching hospital. A total of 168 patients were randomly assigned to the mind-body (MBPI) group (n = 84) and the fertility support (FS) control group (n = 84). Patients received a 10-week, 135-min/week group intervention, with the FS group following the same format as the MBPI group, but with a less restricted and systematic content, and without the presumed effective factors. The number of patients analysed was n = 74 (MBPI) and n = 68 (FS) for post-intervention psychological outcomes, and n = 54 (MBPI) and n = 56 (FS) for pregnancy outcomes at a 30-month follow-up. Significant improvements occurred in both groups in all psychological domains (adjusted P < 0.001), except for treatment-related quality of life. Linear mixed-model regression analysis did not reveal significantly greater pre-post improvements in the MBPI group than in the FS group in fertility-related quality of life (difference in differences (DD) = 4.11 [0.42, 7.80], d = 0.32, adjusted P = 0.124), treatment-related quality of life (DD = -3.08 [-7.72, 1.55], d = -0.20, adjusted P = 0.582), infertility-specific stress (DD = -2.54 [-4.68, 0.41], d = -0.36, adjusted P = 0.105), depression (DD = -1.16 [3.61, 1.29], d = -0.13, adjusted P = 0.708), and general stress (DD = -0.62 [-1.91, 0.68], d = -0.13, adjusted P = 0.708), but it did show a significantly larger improvement in trait anxiety (DD = -3.60 [-6.16, -1.04], d = -0.32, adjusted P = 0.042). Logistic regression showed no group effect on MAR pregnancies, spontaneous pregnancies, or live births. The follow-up only covered MAR-related medical outcomes and no psychological variables, and their rates were not equal in the two groups. Biological factors other than age, aetiology, and duration of infertility may have confounded the study results. Loss to follow-up was between 5% and 10%, which may have led to some bias. The psychologically and medically heterogeneous sample, the normal clinical setting and the low attrition rate all raise the external validity and generalizability of our study. The MBPI works not only in controlled conditions, but also in routine MAR practice, where it can be introduced as a cost-effective, low-intensity psychological intervention, within the framework of stepped care. More studies are needed to further identify its active ingredients. The authors received no financial support for the research, authorship, and/or publication of this article. The authors have no conflict of interest to disclose. ClinicalTrials.gov NCT04151485. 5 November 2019. 15 December 2019.

Superiority of opioid free anesthesia with regional block over opioid anesthesia with regional block in the quality of recovery after retroperitoneiscopic renal surgery: a randomized controlled trial.

Opioids are the main analgesic drugs used in the perioperative period, but they often have various adverse effects. Recent studies have shown that quadratus lumborum block (QLB) has an opioid sparing effect. The aim of this study was to further evaluate the effect of opioid-free anesthesia (OFA) combined with regional block on the quality of recovery in patients undergoing retroperitoneoscopic renal surgery. Sixty patients undergoing elective retroperitoneoscopic renal surgery were divided into the opioid-free anesthesia with quadratus lumborum block group (OFA group, N.=30) and opioid anesthesia with quadratus lumborum block group (OA group, N.=30) using the random number table method. The main outcome measures were the quality of recovery assessed by Quality of Recover-40 (QoR-40) at the 24th postoperative hour. Secondary outcomes were postoperative pain score, postoperative opioid consumption, postoperative nausea and vomiting, time to ambulate, and time to readiness for discharge. The QoR-40 score on the first postoperative day was significantly higher in the OFA group than that in the OA group (175.41±6.74 vs. 165.07±4.55; P<0.05). OFA also significantly reduced postoperative pain (P<0.05) and morphine consumption at both the 24th and 48th postoperative hour (P<0.05), as well as time to ambulate, and time to readiness for discharge (P<0.05). OFA with regional block is superior to opioid anesthesia with regional block in the quality of recovery after retroperitoneiscopic renal surgery.